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BackgroundThe role of individual-tailored dietary recording in mobile phone health apps has become increasingly important in management of self-health care and population-based preventive service. The development of such mobile apps for user-centered designing is still challengeable and requires further scientific evidence. ObjectiveThis study aims to conduct a randomized trial to assess the accuracy and time efficiency of two prototypes for dietary recoding utilization related to the input method of food intake. MethodsWe first present an innovative combinatorial concept for dietary recording to account for dish variation. One prototype was a self-chosen tab app that featured choosing each food ingredient to synthesize an individual dish, whereas the other was an autonomous exhaustive list app that provided one selection from a comprehensive list of dish items. The concept included commercially available choices that allowed users to more accurately account for their individual food selection. The two mobile apps were compared in a head-to-head parallel randomized trial evaluation. Young adults (n=70, aged 18-29) and older adults (n=35, aged 55-73) were recruited and randomized into two groups for accuracy and response time evaluation based on 12 types of food items in use of the developed self-chosen tab and autonomous exhaustive list apps, respectively. ResultsFor the trials based on the self-chosen tab (53 participants) and autonomous exhaustive list groups (52 participants), the two prototypes were found to be highly accurate (>98%). The self-chosen tab app was found to be more efficient, requiring significantly less time for input of 11 of 12 items (P

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

Objectives: The primary aim was to determine the prevalence of gastrointestinal diseases in patients with chronic rhinosinusitis (CRS), utilizing the National Health Insurance Research Database (NHIRD) in Taiwan. Several studies have supported the existence of distinct immune patterns between the Asian and Western populations in CRS patients. Through the population-based case-control study, we could compare the differences between various regions and provide further treatment strategies for subsequent studies in Asian CRS patients. The secondary aim was to assess whether different types of CRS influence the correlation with specific GI diseases. Understanding how different phenotypes or endotypes of CRS may relate to distinct GI disease patterns could provide valuable insights into the underlying mechanisms and potential shared pathways between these conditions. Methods: We use the NHIRD in Taiwan. Newly diagnosed patients with CRS were selected between January 1, 2001 and December 31, 2017 as the case group, and the controls were defined as individuals without a history of CRS. Patients with CRS were divided into two groups: with nasal polyps and without nasal polyps. We also separated GI tract diseases into four groups based on their different pathophysiologies. Results: This study included 356,245 participants (CRS: 71,249 and control: 284,996). The results showed that CRS was significantly associated with some specific GI tract diseases, including acute/chronic hepatitis B, gastroesophageal reflux disease (GERD) with/without esophagitis, achalasia of cardia, peptic/gastrojejunal ulcer, Crohn's disease, and ulcerative colitis. In addition, when CRS was subcategorized into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP), GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. Conclusions: A significant association between CRS and premorbid GI tract diseases has been identified. Remarkably, GERD with esophagitis and peptic ulcer were significantly associated with CRSsNP. The underlying mechanisms require further investigation and may lead to new treatments for CRS. Researchers can further investigate the mechanisms by referring to our classification method to determine the implications for diagnosis and treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Otomastoiditis caused by mycobacterial infections is uncommon and recalcitrant. Its clinical presentations, sometimes similar to those of common chronic suppurative otitis media, make diagnosis difficult. This retrospective study analyzed the clinical features, treatment course, and therapeutic outcomes of patients with mycobacterial otomastoiditis. The cases of six patients diagnosed with mycobacterial otomastoiditis or suspected mycobacterial infection between January 2007 and January 2019 in a single tertiary medical center in Taiwan were investigated. Information about predisposing factors, clinical features, culture reports, histopathology, treatment course, and outcomes were collected and analyzed. Relevant literature available in English was also reviewed. One patient was infected with tuberculous mycobacteria, two with suspected tuberculous mycobacteria, and three with nontuberculous mycobacteria. All six patients responded poorly to empiric antibiotic therapy, and diagnosis was not possible at their previous clinics. Five patients underwent tympanomastoidectomies; one was administered antimycobacterial medication without undergoing surgery. Mycobacterial infection was confirmed from a tissue culture or from the histopathology of the specimen, but in two patients, no definitive evidence of tuberculosis was found. Antimycobacterial medication was administered based on clinical suspicion, and improvement was noted. With appropriate therapy, all patients recovered, and no sequelae were observed after treatment. If empiric antibiotic therapy cannot achieve acceptable results, atypical infections, such as mycobacteria, should be considered. Antimycobacterial medication could be administered under clinical suspicion, serving as a diagnosis ex juvantibus. Surgical intervention might help reduce the bacterial load and obtain specimens for accurate diagnosis, but this may be unnecessary if appropriate antimycobacterial medication results in improvement. Early diagnosis and treatment can prevent complications in patients with recalcitrant otomastoiditis.

Background: The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre-operative diagnostic criteria for patients with ECRS in Taiwan., Methods: This case-control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non-eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS., Results: Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p  = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p  < .01), higher serum IgE (285.3 vs. 50.2 IU/mL, p  = .02), and higher 22-item Sino-Nasal Outcome Test (SNOT-22) score (40.5 vs. 36.7, p  = .03). The ECRS criteria based on ROC curve included the SNOT-22 (>45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund-Mackay score (>9.5, 4 points), and ethmoid-to-maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%)., Conclusions: Clinical-feature-based criteria may predict the diagnosis of ECRS before FESS in Taiwan., Level of Evidence: Level 3., Competing Interests: The authors declare no conflicts of interest relevant to this report., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: The objective of this research is to compare primary and salvage intratympanic (IT) steroid treatments in terms of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL)., Methods: The patients were randomized into two (primary and salvage) groups. Both groups received systemic steroid treatment for 2 weeks. The primary group also received IT dexamethasone injection three times during the treatment period, whereas the salvage group received IT dexamethasone injection only if no or slight recovery was noted at the 2-week follow-up. If needed, salvage steroid injection was administered three times during the following 2 weeks. Hearing recovery was analyzed according to the modified American Academy of Otolaryngology-Head and Neck Surgery criteria., Results: The degrees of hearing improvement at the 3-month follow-up were similar in the two groups. Compared with baseline, the pure-tone average values and speech discrimination scores improved by 38.45 ± 21.95 dB HL and 34.32% ± 30.55%, respectively, in the primary group and 36.80 ± 22.33 dB HL and 31.87% ± 27.88%, respectively, in the salvage group ( p  = .762 and .659, respectively). In addition, the complete or partial hearing recovery rates were also similar in the primary and salvage groups (67.7% vs. 73.3%, respectively; p  = .780). In the salvage group, 18 patients required no IT steroid injection because they recovered after systemic steroid treatment., Conclusion: Primary and salvage IT steroid treatments for ISSNHL led to similar outcomes. In summary, salvage IT steroid injection is recommended for patients with ISSNHL patients to prevent unnecessary IT injection., Level of Evidence: 2., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background/aims: Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS., Methods: In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured., Results: Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH- (ILPRS in pH+ vs pH-: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH-: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH- subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH- subgroup and healthy controls ( P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001)., Conclusion: Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Background/aims: Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility., Methods: We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed., Results: A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%., Conclusion: Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Docetaxel (DTX) combined with cisplatin and 5-fluorouracil has been used as induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). However, the development of acquired resistance remains a major obstacle to treatment response. Tumor-associated macrophages are associated with chemotherapeutic resistance. In the present study, increased infiltration of macrophages into the tumor microenvironment (TME) was significantly associated with shorter overall survival and increased resistance to chemotherapeutic drugs, particularly DTX, in patients with HNSCC. Macrophage coculture induced expression of intercellular adhesion molecule 1 (ICAM1), which promotes stemness and the formation of polyploid giant cancer cells, thereby reducing the efficacy of DTX. Both genetic silencing and pharmacological inhibition of ICAM1 sensitized HNSCC to DTX. Macrophage secretion of IL-1β was found to induce tumor expression of ICAM1. IL-1β neutralization and IL-1 receptor blockade reversed DTX resistance induced by macrophage coculture. IL-1β activated superoxide dismutase 2 and inhibited catalase, thereby modulating intracellular levels of ROS and inducing ICAM1 expression. Arsenic trioxide (ATO) reduced macrophage infiltration into the TME and impaired IL-1β secretion by macrophages. The combinatorial use of ATO enhanced the in vivo efficacy of DTX in a mouse model, which may provide a revolutionary approach to overcoming acquired therapeutic resistance in HNSCC.

The main aim of this study is to compare the incidence rate and severity of deep neck infection (DNI) in patients post-UPPP+ T (uvulopalatopharyngoplasty plus tonsillectomy) and without UPPP+ T. We utilized the data derived from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD) in Taiwan from 1 January 2000 to 31 December 2012. Patients who had undergone combined UPPP and tonsillectomy were selected using National Health Insurance (NHI) surgical order. Patients with DNI were selected using International Classification of Diseases (ICD-9-CM) code. A logistic regression model was applied for risk analysis. There were 1574 patients in the UPPP+ T cohort, and 6,296 patients who did not undergo combined UPPP and tonsillectomy for the control group. Our analysis showed that patients with an obstructive sleep apnea syndrome (OSAS) history constitute 76.1% ( n = 1198) of the UPPP+ T cohort. Compared to the control group, there was no significantly increased incidence rate of DNI after UPPP+ T within 1-60 months. Patients undergoing combined UPPP and tonsillectomy had a lower intubation rate for DNI, with an adjusted odds ratio of 0.47 (95% CI = 0.32-0.69). The combined UPPP and tonsillectomy does not increase the risk of DNI within 1-60 months. Furthermore, combined UPPP and tonsillectomy can reduce the severity for DNI by decreasing the intubation rate and length of hospitalization.

Obesity is a worldwide health problem. Calorie-restricted diets constitute a common intervention for treating obesity. However, an improper calorie-restricted diet can lead to malnutrition, fatigue, poor concretion, muscle loss, and reduced exercise performance. Probiotics have been introduced as an alternative treatment for obesity. In the present study, we tested the weight loss and exercise performance enhancement effectiveness of probiotic strains of different origins, including four isolated from an Olympic weightlifting gold medalist ( Bifidobacterium longum subsp. longum OLP-01, Lactobacillus plantarum PL-02, Lactobacillus salivarius subsp. salicinius SA-03, and Lactococcus lactis subsp. lactis LY-66). A high-fat diet (HFD) was used to induce obesity in 16 groups of mice ( n = 8/group). The mice were administered probiotic supplements at a dosage of 4.1 × 10 9 CFU/kg/day for 10 weeks. All probiotic supplementation groups showed a significant reduction in body weight and fat mass compared with the HFD group. TYCA06, CS-773, BLI-02, PL-02, bv-77, and OLP-01 were the most effective in facilitating weight loss and fat reduction, which may be due to fatty-acid absorbing activity. PL-02, LY-66, TYCA06, CS-773, and OLP-01 elevated the animals' grip strength and exhaustive running duration. PL-02, LY-66, and OLP-01 increased tissue glycogen (liver and muscle) levels and muscle capillary density and reduced blood lactate production levels after exercise. In conclusion, OLP-01, PL-02, LY-66, TYCA06, and CS-773 were highly effective in enhancing weight loss and exercise performance. This study should be repeated on humans in the future to further confirm the findings.

This is a retrospective longitudinal study that uses data from the National Health Insurance Research Database (NHIRD) of Taiwan of which hypothyroid patients who received a diagnosis between 2000 and 2010 were selected and followed up until 2011. The primary outcome of this study was the occurrence of tinnitus (ICD-9-CM code 388.3). The relevant comorbidities were selected as potential confounders according to the literature, which included vertigo (ICD-9-CM code 386), insomnia (ICD-9-CM code 780), anxiety (ICD-9-CM code 300.00), and hearing loss (ICD-9-CM code 388-389). The overall incidence of tinnitus was significantly higher in the hypothyroidism cohort than in the non-hypothyroidism cohort (9.49 vs. 6.03 per 1000 person-years), with an adjusted HR of 1.35 (95% CI 1.18-1.54) after adjusting potential confounders. The incidences of tinnitus, as stratified by gender, age, comorbidity, and follow-up time, were all significantly higher in the hypothyroidism cohort than those in the non-hypothyroidism cohort. The incidence of tinnitus significantly increased with age (aHR = 1.01, 95% CI 1.01-1.02). In conclusion, we report the relationship between hypothyroidism and the increased risk for tinnitus. We also found that hypothyroidism patients are at increased risk of developing tinnitus when associated with comorbidities including vertigo, hearing loss, and insomnia., (© 2022. The Author(s).)

Athletes often have poor sleep quality before a competition. Sleep quality can stabilize mood and improve sports performance. The randomized controlled study explored the effects of cranial electrotherapy stimulation (CES) on the physiology, psychology, response-ability, and sleep quality of athletes who had poor sleep quality before a competition. Athletes who had poor sleep quality (Pittsburgh Sleep Quality Scale score > 5) and had a competition in less than 2 months were recruited. The athletes were grouped into the CES group, which received a 2-week CES treatment ( n = 20, age = 21.55 ± 2.26 years), and a placebo group ( n = 20, age = 21.05 ± 1.46 years), which received a 2-week sham CES treatment. We performed biochemical analysis, a simple reaction time test, choice reaction time tests, the Profile of Mood States, heart rate variability (HRV), and an Actigraphy activity recorder to measure outcomes before and after the interventions. Our results revealed no significant differences in blood urea nitrogen, creatine phosphate, testosterone, cortisol, and saliva pH between and within groups ( p > 0.05). Significant decreases in negative mood states (i.e., anger, tension, and depression) and choice reaction time in the CES group were noted ( p < 0.05), moreover, the anger, tension, and depression mood decreased from 0.36 ± 0.45 (95% CI = 0.16-0.55), 1.62 ± 0.97 (95% CI = 1.19-2.04), and 1.67 ± 1.06 (95% CI = 1.20-2.13) to 0.11 ± 0.20 (95% CI = 0.02-0.19, p = 0.03), 1.12 ± 0.74 (95% CI = 0.79-1.44, p = 0.04), and 0.81 ± 0.75 (95% CI = 0.48-1.13, p = 0.001), respectively. Additionally, choice reaction time was decreased from 420.85 ± 41.22 ms (95% CI = 402.78-438.91) to 399.90 ± 36.71 ms (95% CI = 383.81-415.98, p = 0.04) and was also noted in the CES group. For HRV, and Actigraphy activity for sleep measure, the low-frequency (LF)/high-frequency (HF) ratios changed from 1.80 ± 1.39 (95% CI = 1.19-2.40) to 1.21 ± 0.73 (95% CI = 0.89-1.53, p = 0.10), and sleep efficiency decreased from 87.94 ± 6.76% (95% CI = 84.97-90.90) to 81.75 ± 9.62% (95% CI = 77.53-85.96, p = 0.02) in the CES group. The change in LF/HF after the trial were found between CES and placebo groups (p < 0.05). Yet, the decrease in sleep efficiency in the placebo group were noted ( p < 0.05). However, we found that the regression line for sleep efficiency was decreased less during the study while using CES. The CES intervention could reduce negative emotions, improve choice reaction times, enhance the parasympathetic and sympathetic nerve activity imbalances, and slow sleep efficiency deterioration. Regardless, small effect sizes of the application of CES on psychology response, response-ability, and sleep efficiency were concluded in athletes with poor sleep quality before a competition.

Sulcus vocalis is a frequent cause of glottic insufficiency that leads to incomplete vocal fold closure during phonation. Type II sulcus vocalis is defined as a partial defect of the lamina propria (LP). Treatment with fillers, such as fat or hyaluronic acid (HA), in the vocal folds is widely used, but the duration of effect is variable. Platelet-rich plasma (PRP) can enhance the survival of autologous fat in fat grafting, and also is used to treat sulcus vocalis. This study aimed to compare the effectiveness of autologous fat graft versus fat graft plus PRP to treat type II sulcus vocalis. Thirty-four patients with a voice handicap index (VHI) ≥ 11 were randomized to two groups, which received LP injections of fat graft ( n = 17) or fat graft plus PRP ( n = 17). At 1 month and 6 months after injection, the VHI decreased significantly in both groups. The fat plus PRP group had better Jitter, Shimmer, and noise to harmonic ratio (NHR) in 1 month and 6 months after surgery. The fat plus PRP group resulted in lower VHI scores one month after surgery, and stroboscopy revealed sustained smaller gaps after six months. These results indicate that a combination of fat graft plus PRP is safe and effective for treating sulcus vocalis type II and associated vocal atrophy.

Laryngopharyngeal reflux disease (LPRD) might be associated with reflux symptoms, and its severity is correlated with the Reflux Symptoms Index. Diagnosis is often challenging because of a lack of accurate diagnostic tools. Although an association between LPRD and gastroesophageal reflux disease (GERD) exists, the extent to which esophageal pressure changes in patients with LPRD with GERD has been unknown. Therefore, this study surveys the clinical assessments and extent of esophageal pressure changes in LRPD patients with various GERD severities, and compares esophageal sphincter pressures between ages, genders, and body mass index (BMI). This observational study assessed patients with LPRD and GERD. High-resolution esophageal manometry was used to gather data pertaining to the area pressure on the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), and the correlation between such pressure and symptom severity was determined. We compared the esophageal pressure of different UES and LES levels in the following categories: gender, age, BMI, and GERD severity. We analyzed correlations between esophageal pressure and clinical assessments among 90 patients with throat globus with laryngitis with LPRD. LPRD was measured using laryngoscopy, and GERD was measured using esophagoscopy and 24 h PH monitoring. There were no significant differences in the clinical assessments among the four grades of GERD. The LPRD patients with serious GERD had a lower UES and LES pressure. The lowest pressure and longer duration of LES and UES were also observed among patients with LPRD of grade D GERD. No significant differences in UES and LES pressures among ages, genders, or BMIs were noted.

Background: Unilateral vocal palsy (UVFP) affects the voice and swallowing function and could be treated by various materials to achieve improved mucosal wave and better closure during phonation. Injection laryngoplasty is considered an exemplary method for these patients and could be injected as early as possible. We conducted a systematic review and meta-analysis for the subjective and objective outcomes of autologous fat injection laryngoplasty (AFIL) and assessed the effects for patients with UVFP., Methods: We searched studies from PubMed and EBSCO databases with PRISMA appraisal to search for articles about the effects of AFIL on UVFP. The published articles were reviewed according to our inclusion and exclusion criteria. The short- and long-term outcomes of perceptual, acoustic analysis, and quality of life were also analyzed by meta-analysis., Results: Eleven articles were reviewed, and seven studies were selected for meta-analysis. AFIL improves the perceptual outcome and some voice parameters in short-term and long-term results, i.e., jitter, shimmer, and maximal phonation time (MPT). It also significantly improved the voice handicap index (VHI) in the long term, suggesting an increase in quality of life., Conclusions: AFIL is considered a reliable treatment method for UVFP and could even last for over 12 months.

Background: Successful surgery outcomes are limited to moderate to severe obstructive sleep apnea (OSA) syndrome. Multilevel collapse at retropalatal and retroglossal areas is often found during the drug-induced sleep endoscopy (DISE). Therefore, multilevel surgery is considered for these patients. The aim of our study was to survey surgical outcomes by modified uvulopalatoplasty (UPPP) plus transoral robotic surgery tongue base reduction (TORSTBR) versus barbed repositioning pharyngoplasty (BRP) plus TORSTBR., Methods: The retrospective cohort study was performed at a tertiary referral center. We collected moderate to severe OSA patients who were not tolerant to positive pressure assistant PAP from September 2016 to September 2019; pre-operative-operative Muller tests all showed retropalatal and retroglossal collapse; pre-operative Friedman Tongue Position (FTP) > III, with the tonsils grade at grade II minimum, with simultaneous velum (V > 1) and tongue base (T > 1), collapsed by drug-induced sleep endoscopy (DISE) under the VOTE grading system. The UPPP plus TORSTBR ( n = 31) and BRP plus TORSTBR ( n = 31) techniques were offered. We compare the outcomes using an Epworth sleepiness scale (ESS) questionnaire, and measure the patients' apnea-hypopnea index (AHI), lowest O 2 saturation, cumulative time spent below 90% (CT90), and arousal index (AI) by polysomnography six months after surgery; we also measure their length of hospital stay and complications between these two groups., Results: Comparing BRP plus TORSTBR with UPPP plus TORSTBR, the surgical success rate is 67.74% and 38.71%, respectively. The significantly higher surgical success rate in the BRP plus TORSTBR group was noted. The surgical time is shorter in the BRP plus TORSTBR group. The complication rate is not significant in pain, bleeding, dysgeusia, dysphagia, globus sensation, and prolonged suture stay, even though the BRP plus TORSTBR rendered a higher percentage of globus sensation during swallowing and a more prevalent requirement of suture removal one month after surgery. The length of hospital stay is not significantly different between the two groups., Conclusion: In conclusion, BRP plus TORSTBR is a considerable therapy for moderate to severe OSA patients with DISE showing a multi-level collapse in velum and tongue base area. The BRP technique might offer a better anterior-posterior suspension vector for palate level obstruction.

Lung cancer is heterogeneous and challenging to cope with once it has progressed. Chemotherapy is the first step once no active driver mutation has been discovered. Non-antitumor drugs have been found to be beneficial when used as adjuvants to chemotherapy. In this study, the additive effect and mechanism of metformin combined with pemetrexed in non-small-cell lung cancer (NSCLC) cells were elucidated. Three NSCLC cell lines, A549, H1975, and HCC827, were used to analyze tumor cell proliferation, colony formation and the cell cycle in vitro when exposed to metformin alone, pemetrexed alone or their combination. We found that combination treatment in three cell lines exerted antiproliferative effects through cell cycle arrest in the S phase. An ex vivo chicken chorioallantoic membrane (CAM) assay was used to examine the antiangiogenic effect of metformin combined with pemetrexed on vascular structure formation. We further created an A549 orthotopic xenograft model with an in vivo imaging system (IVIS) and explored the associated indicators involved in the tumorigenic process. The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase. For antiangiogenic effects, the combination therapy inhibited the vascular structure, as proven by the CAM assay. We elucidated that combination therapy could target VEGFA and Endoglin by RT-qPCR, ELISA and histopathological findings in an A549 orthotopic NSCLC xenograft model. Our research demonstrated the additive antiproliferative and antiangiogenic effects of the combination of metformin with pemetrexed in NSCLC and could be applied to clinical lung cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Lan, Tsai, Chen, Staniczek, Tsou, Yen and Chen.)

We explored the effects of 6-week whole-body vibration (WBV) and balance training programs on female athletes with chronic ankle instability (CAI). This randomized controlled study involved female athletes with dominant-leg CAI. The participants were randomly divided into three groups: WBV training (Group A), balance training (Group B), and nontraining (control group; Group C). Groups A and B performed three exercise movements (double-leg stance, one-legged stance, and tandem stance) in 6-week training programs by using a vibration platform and balance ball, respectively. The Star Excursion Balance Test (SEBT), a joint position sense test, and an isokinetic strength test were conducted. In total, 63 female athletes with dominant-leg CAI were divided into three study groups (all n = 21). All of them completed the study. We observed time-by-group interactions in the SEBT ( p = 0.001) and isokinetic strength test at 30°/s of concentric contraction (CON) of ankle inversion ( p = 0.04). Compared with the control group, participants of the two exercise training programs improved in dynamic balance, active repositioning, and 30°/s of CON and eccentric contraction of the ankle invertor in the SEBT, joint position sense test, and isokinetic strength test, respectively. Furthermore, the effect sizes for the assessed outcomes in Groups A and B ranged from very small to small. Female athletes who participated in 6-week training programs incorporating a vibration platform or balance ball exhibited very small or small effect sizes for CAI in the SEBT, joint position sense test, and isokinetic strength test. No differences were observed in the variables between the two exercise training programs.

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPKα and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.

Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case-control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28-1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34-1.67], 3.47 [1.12-10.8], 1.22 [1.04-1.43], 1.60 [1.31-1.96], 2.10 [1.63-2.72], and 1.69 [1.26-2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14-1.58] and 1.50 [1.38-1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72-2.49] and 1.39 [1.28-1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

This study compared the characteristic surgical parameters and clinical effects of transoral robotic surgery (TORS) and other available methods used to alleviate obstructive sleep apnea. Articles on TORS and other surgeries for obstructive sleep apnea were identified in the PubMed and EMBASE databases. Two investigators independently reviewed the articles and classified the data for meta-analysis. The pooled effect sizes of TORS (standardized mean difference; SMD = - 2.38), coblation tongue base resection (CTBR; SMD = - 2.00) and upper airway stimulation (UAS; SMD = - 0.94) revealed significant improvement in the apnea-hypopnea index (AHI; p < 0.05). The lowest O 2 saturation reported was significantly increased following TORS (SMD = 1.43), CTBR (SMD = 0.86) and UAS (SMD = 1.24, p < 0.05). Furthermore, TORS (SMD = - 2.91) and CTBR (SMD = - 1.51, p < 0.05) significantly reduced the Epworth Sleepiness Scale (ESS) score. No significant difference in operation time, success rate, or instances of complication were observed between TORS and the other compared interventions. The use of TORS in obstructive sleep apnea has the same rate of success and failure as other methods of surgical intervention for obstructive sleep apnea with no statistical difference in operation times. The reported clinical effects on the AHI, lowest O 2 saturation, and ESS scores of TORS were similar to those of other surgeries.

A higher incidence rate of nocturia in patients with obstructive sleep apnea (OSA) has been observed. We investigated the differences in clinical examinations between OSA patients with and without nocturia, and further compared those with successful and unsuccessful uvulopalatopharyngoplasty (UPPP). This retrospective study enrolled 103 patients with OSA undergoing UPPP. Patients were diagnosed with OSA by following the 2018 American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.5. Patients were divided into two groups depending on if they urinated more than twice per night. The medical data of body mass index (BMI), nocturia frequency per night, apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), International Prostatic Symptom Score (IPSS), and Overactive Bladder Symptom Score (OABSS) were analyzed before and after uvulopalatopharyngoplasty (UPPP) surgery. All of the measurements were compared between successful and unsuccessful surgery in the non-nocturia or nocturia groups, respectively. Fifty patients (41 males and nine females) without nocturia were assigned to group 1, and 53 patients (43 males and 10 females) with nocturia were assigned to group 2. Nocturia frequency and post-surgery AHI in group 2 were significantly higher than those in group 1 ( p < 0.05). Significant decreases in IPSS and OABSS were observed in the successful surgery subgroup of group 2 ( p < 0.05). A significant decrease in post-surgery AHI was observed between unsuccessful and successful surgery in patients with nocturia ( p < 0.05), but not in the non-nocturia group ( p > 0.05). Although AHI had a significant correlation to nocturia frequency in all OSA patients before UPPP, no significant correlation between AHI reduction and nocturia frequency was found. UPPP appeared to be an effective treatment for nocturia associated with OSA. OSA should be taken into consideration for patients who complain of nocturia syndrome. The relationship of AHI reduction and nocturia improvement after OSA treatment with UPPP is still unclear. In addition, it is necessary to establish the existence of nocturia in patients with OSA, as a result of its high prevalence in OSA patients. UPPP could reduce the symptoms of OSA and could also contribute to a reduction of nocturia even in the unsuccessful surgery group.

The Velum, Oropharynx, Tongue base and Epiglottis (VOTE) classification on drug-induced sleep endoscopy (DISE) is used widely for obstructive sleep apnea (OSA) syndrome, though research into comparative physical examinations with VOTE on DISE is still limited. The aim of this study was to evaluate the relationship between the findings of physical examinations and DISE in patients with OSA. Fifty-five patients with OSA were enrolled in this retrospective study. All of the patients received clinical explorations including a Brodsky classification, a modified Mallampati score (MMS), a modified Friedman's staging system, and a Muller's test. Drug-induced sleep endoscopy was further evaluated in the operating room. There were significant relationships between Brodsky classification, modified Friedman's staging system, Muller's test and oropharynx collapse during DISE ( p < 0.05). Brodsky classification, MMS, modified Friedman's staging system and retropalatal lateral-to-lateral (L-L) collapse of Muller's test were significantly correlated with VOTE count ( p < 0.05). The concordance between VOTE under DISE and Brodsky classification or modified Friedman's staging system was moderate. In contrast, the concordance between VOTE under DISE and MMS or Muller's test was slight. The study revealed that Brodsky classification and Friedman staging had a significant relationship with DISE on the velum and oropharynx, but the level of tongue base is uncertain between DISE and MMS. Correlation of awake evaluation of tongue base is still not correlated to the DISE findings. Pre-treatment evaluation of DISE is still warranted.

Background & Aims: Patients with isolated laryngopharyngeal reflux symptoms (LPRS) defined as those without concomitant typical reflux symptoms (CTRS) are clinically challenging to manage due to unclear pathophysiology. We investigated esophageal physiology in patients with isolated LPRS and their response to proton-pump inhibitors (PPI) therapy., Methods: This is a multi-center observational study conducted in referral hospitals in Taiwan. Patients with predominant LPRS, but without common non-reflux causes, underwent esophageal manometry, 24-hr ambulatory esophagopharyngeal pH testing, and Bernstein test, followed by a 12-week esomeprazole 40 mg twice-daily treatment. Participants with pathological reflux were divided into the isolated LPRS group (ie, LPRS without CTRS, n = 40) and the CTRS group (ie, LPRS with CTRS, n = 66). Participants without pathological reflux or esophagitis (n = 132) served as the nonreflux controls., Results: The PPI-responsiveness was similar between the isolated LPRS group and CTRS group (63% vs 57%, P = .8), but lower in the nonreflux controls (32%, P = .005). Despite similar distal esophageal acid exposure time (P = .7) when compared to those with CTRS, the isolated LPRS group had a lower prevalence of both positive Bernstein test (P = .001) and ineffective esophageal motility disorder (P = .03), and fewer pharyngeal acid reflux episodes (P < .0001)., Conclusions: Our findings indicate similar distal esophageal acid exposure and PPI-responsiveness between LPRS patients with and without CTRS. The lack of CTRS in the isolated LPRS group is likely due to esophageal acid hyposensitivity and fewer pharyngeal acid reflux episodes, thus implicating distinct pathophysiology of isolated LPRS from those with CTRS., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Pediatric sleep-disordered breathing (SDB) correlated with respiratory conditions of snoring and hypopnea. Mean platelet volume (MPV) was an inflammatory marker, related to increased inflammatory condition of pediatric patients. Increase of MPV level may cause failure to thrive or increased upper airway infection rate. The aim of this study was to perform systematic review and meta-analysis to investigate the difference on MPV values for pediatric SDB, and compare the change on MPV after surgery in patients with pediatric SDB., Methods: A systemic review of the studies from PubMed, EMBASE, and Cochrane Library databases was conducted in March 2020, supported by reviewing of published articles for studies comparing MPV in pediatric SDB. Meta-analysis was used to compare the change of MPV in pediatric SDB, and sub-group analysis was also used to compare the MPV decrease after surgeries of adenoidectomy or adenotonsillectomy., Results: There were seven studies included in the review. Six of them including 963 subjects showed that a significant increase of MPV was noted in pediatric SDB compared to those in pediatric non-SDB (P < 0.05). Total standardized mean difference (SMD) in MPV between pediatric SDB and non-SDB was 0.51 (95% CI =0.30-0.72, P < 0.05). A significant decrease of MPV was found in pediatric SDB patients who underwent surgery (total SMD = - 0.36; 95% CI = - 0.70- -0.02, P < 0.05). Decreases of MPV after adenoidectomy and adenotonsillectomy were observed, but only the effect of adenotonsillectomy had a statistical significance (total SMD = - 0.72; 95% CI = - 1.18 - -0.26, P < 0.05)., Conclusion: The MPV was significantly higher in patients with pediatric SDB, indicating the presence of increased platelet activity in pediatric SDB patients. The level of MPV could be reduced by the two surgeries, especially adenotonsillectomy.

Background: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk., Methods: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti-EBV VCA IgA and anti-EBV EA-EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders., Results: 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60-fold (95% CI = 1.30-1.97) and former smokers a borderline significant 1.27-fold (95% CI = 1.00-1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack-years of cigarette smoking but not with age at smoking initiation. Among controls, anti-EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19-2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti-EBV VCA IgA., Conclusion: This study confirms the association between long-term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti-EBV VCA IgA antibodies., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The aim of this study was to compare major voice indicators in different sub-categories, the outcome of lipoinjection for patients might be refined and some voice prognostic factors could be more particularized in specific sub-groups. This is an observational study, and sub-grouped UVFP patients into 3 categories: male vs female, BMI ≥ 24 vs BMI < 24, Age ≥ 60 vs Age < 60 for more detailed exploring whether sub-categories affected voice diagnostic and prognostic parameters. Patients' voice data is recorded before and after the autologous fat injection laryngoplasty by a multidimensional voice program. Overall, 73 patients' voice performance were improved 12 months later by vocal fold lipoinjection. In the comparison of the male with female revealed female obtained better Jita than male by surgery (Female: 174.50 ± 100.58 Hz; Male: 294.82 ± 253.65 Hz; P < .05). BMI ≥ 24 vs BMI < 24 showed no statistical difference. Patients aged under 60 demonstrated better Highest F0, lowest F0, NHR and ShdB than elder ones 12 months after receiving vocal fold lipoinjection. Thus, Noise-to-harmonics ratio (NHR), voice turbulence index (VTI), and ShdB (Absolute shimmer, dB) may be the major post-operative evaluating markers of patients' age under 60. Voice parameters showed no significant correlation with BMI. Female patients performed lower Jita (Absolute jitter, μsec) than male patients 1 year after receiving treatment. The experimental results in this study showed UVFP patients' gender and age may stand as significant categories on analyzing clinical voice prognostic indicators, ShdB and Jita of autologous injection laryngoplasty.

Objectives: To compare the efficacy of trans-oral robotic surgery (TORS) with that of coblation assisted tongue base reduction surgery in patients with obstructive sleep apnea syndrome (OSAS)., Subjects and Methods: The medical charts were retrospectively reviewed for all OSAS patients admitted to one institution for surgical intervention between 2012 and 2017. We analyzed 33 cases; 16 patients received TORS and 17 received coblation surgery for tongue base reduction. Both groups received concomitant uvulopalatoplasty. Surgical outcomes were evaluated by comparing the initial polysomnography (PSG) parameters with the follow-up PSG data (at least 3 months after the surgery). Epworth sleepiness scale (ESS) and complications were also compared between the 2 groups., Results: The success rate (≥50% reduction of pre-operative AHI and post-operative AHI <20) in the TORS group and coblation group were 50% and 58%, respectively, and there was no significant difference ( p  = .611). The AHI (mean ± SD) reduction in the TORS and coblation groups were 24.9 ± 26.5 events/h and 19.4 ± 24.8 events/h, respectively; the between-group difference was not significant ( p  = .631). ESS improvement did not differ significantly between the TORS and coblation groups (3.8 ± 6.6 and 3.1 ± 9.2, respectively, p  = .873). The rates of minor complication were higher in the TORS group (50%) than that of the coblation group (35.3%) without statistical significance ( p  = .393)., Conclusion: TORS achieved comparable surgical outcomes compared to coblation assisted tongue base reduction surgery in OSAS patients. Multilevel surgery using either TORS or coblation tongue base reduction combined with uvulopalatoplasty is an effective approach for the management of OSAS., Competing Interests: The authors declare there are no competing interests., (©2019 Lan et al.)

Background: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC., Methods: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted., Results: We found that NPC was associated with combined common and rare variants in CDKN2A/2B ( P = 1.3 × 10 -4 ), BRD2 ( P = 1.6 × 10 -3 ), TNFRSF19 ( P = 4.0 × 10 -3 ), and CLPTM1L/TERT ( P = 5.4 × 10 -3 ). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10 -4 ; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU ( P = 3.8 × 10 -3 ) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs., Conclusions: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC., Impact: NPC-associated genes, including CLPTM1L/TERT, BRD2 , and HNRNPU , suggest a role for telomere length maintenance in NPC etiology., (©2019 American Association for Cancer Research.)

Background: Metformin is proven to improve the prognosis of various cancers, but it is unknown if metformin could ameliorate hypopharyngeal cancer in diabetes mellitus patients. This was a retrospective cohort study, and the effect and survival outcome of metformin on hypopharyngeal cancer with diabetes mellitus was investigated., Methods: There were 141 hypopharyngeal cancer patients collected in a tertiary referral center from December 1st, 2011 to December 31st, 2013. There were 49 patients without diabetes mellitus (DM) and 92 patients with DM. In the 92 DM patients, there were 43 patients with metformin used and 49 patients without metformin used. All received patients followed up until September 1st, 2015., Results: There was no significant difference in patients' characteristics between the non-DM and DM groups, and also no significant difference in clinical T stage, N stage, metastatic condition, and disease stage between the non-DM and DM groups. DM with metformin patients had lower metastasis rates and better overall survival (OS) (p = 0.011) and disease-free survival (DFS) (p = 0.004) compared to non-DM and DM without metformin. Multivariate analysis also showed a better OS and DFS in DM-Met (+) with advanced hypopharyngeal cancer but not in early stage., Conclusion: There was less distant metastasis and better survival outcomes in hypopharyngeal cancer DM patients who use metformin.

The mucosa is part of the first line of immune defense against pathogen exposure in humans and prevents viral and bacterial infection of the soft palate, lungs, uvula, and nasal cavity that comprise the ear-nose-throat (ENT) region. Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is a secretory protein found in human upper aerodigestive tract mucosa. This innate material is secreted in mucosal fluid or found in submucosal tissue in the human soft palate, lung, uvula, and nasal cavity. BPIFA1 is a critical component of the innate immune response that prevents upper airway diseases. This review will provide a brief introduction of the roles of BPIFA1 in the upper airway (with a focus on the nasal cavity, sinus, and middle ear), specifically its history, identification, distribution in various human tissues, function, and diagnostic value in various upper airway infectious diseases.

The objective was to investigate whether tongue base suspension with uvulopalatopharyngoplasty (UPPP) is beneficial on polysomnography analysis for sleep quality in patients with obstructive sleep apnea (OSA) anatomically classified as Fujita type III (small tonsils and a bulky tongue base). In the retrospective study, the charts of 36 patients with OSA that underwent tongue base suspension with UPPP from 2012 through 2015 were reviewed. The surgical outcome measured according to Sher's classification (AHI reduction > 50% and AHI < 20 per hour as success group, otherwise as failure group). The pre- and post-operative sleep quality parameters were evaluated, and the total sleep time changes were evaluated based on electroencephalography study, slow wave sleep, sleep efficiency, rapid eye movement sleep percentile, and Epworth sleep scale scores. Respiratory, the outcomes of polysomnography analysis were then compared between the successful surgery and surgical failure groups during a 1-year follow up. Total arousals and reduced respiratory arousal indices, along with unchanged periodic leg movement and spontaneous electroencephalography arousal indices, were observed in the successful surgery group but not in the surgical failure group. There were 66% resulted in surgical success by this surgery, and 34% as in failure group according to Sher's criteria. Patient sleep quality was further improved by reducing the respiratory arousal index and increasing the rapid eye movement sleep percentile during the 1-year follow up.

Study Objectives: Patients suspected to have sleep-disordered breathing underwent an overnight polysomnography using a divided nasal cannula to gain additional information about the nasal cycle during sleep., Methods: This was a prospective, observational cohort study replacing the undivided nasal cannula with a divided nasal cannula during routine polysomnography (n = 28)., Results: Integration of the divided nasal cannula pressure transducer system into routine polysomnography was easy and affordable. Most patients (89%) demonstrated nasal cycle changes during the test. Nasal cycle changes tended to occur during body position changes (62%) and transitions from non-rapid eye movement sleep to rapid eye movement sleep (41%). The mean nasal cycle duration was 2.5 ± 2.1 hours. Other sleep study metrics did not reveal statistically significant findings in relation to the nasal cycle., Conclusions: Replacing an undivided nasal cannula with a divided nasal cannula is easy to implement, adding another physiologic measure to polysomnography. Although the divided nasal cannula did not significantly affect traditional polysomnographic metrics such as the apnea-hypopnea index or periodic limb movement index based on this small pilot study, we were able to replicate past nasal cycle findings that may be of interest to sleep clinicians and researchers. Given the ease with which the divided nasal cannula can be integrated, we encourage other sleep researchers to investigate the utility of using a divided nasal cannula during polysomnography., (© 2018 American Academy of Sleep Medicine.)

Voice disorder such as vocal fatigue is a common and complex multifaceted clinical problem that presents a significant impact on quality of life. In this study, the functional near-infrared diffuse optical technique (fNIRS-DOT) was proposed as a novel approach for human vocal cords oxidative metabolism detection and acoustic assessment simultaneously to provide a multidimensional assessment of voice disorder. A totally of 60 healthy subjects included 30 male and 30 female adults of age-matched were recruited and performed a vocal loading task to trigger a mild inflammation of the vocal cords in this study. In the results of oxidative metabolism, the vocal cords expressed hypoxia after vocal loading task in both male and female groups that could provide relevant information on the relationship between tissue oxygen consumption and supply for vocal cords diagnosis. Additionally, the results of optical acoustic assessment revealed the worse/changes voice quality after vocal loading task. Therefore, integration of non-invasive oxidative metabolism detection and acoustic assessment by using optical technique could provide more relevant information for diagnosis of voice disorders. The multi-functional vocal cords detection system could provide a good feasibility for clinical applications such as diagnosis and therapeutic monitoring of voice disorder.

Sleep-disordered breathing (SDB) and Eustachian tube disorders (ETDs) share the same risk factors. The specific aim of this study was to determine the correlation between these 2 conditions and to determine whether treatments for SDB reduce the risk of ETD.This is a retrospective and large population-based cohort study. According to Taiwan's National Health Insurance Research Database, out of 1,000,000 insured patients, 24,251 patients were newly diagnosed with SDB from year 2000 through 2009. The control group for this study comprised 96,827 patients without SDB who were randomly selected from the same database at a ratio of 1:4, frequency matched for sex, age, and index year of SDB. The incidence of developing ETD was compared between these 2 groups; the main covariates were demographic data, interventions, and medical comorbidities.There was an increased risk of developing ETD among the SDB cohort compared with the control group (hazard ratio = 1.51, 95% confidence interval = 1.41-1.63). Compared with SDB patients who did not receive treatment, those who received the treatment, that is, pharyngeal or nasal surgery, CPAP, or multiple modalities (both surgery and CPAP), had a significantly reduced risk of developing ETD.This study showed that patients with SDB are at an increased risk of developing ETD and other comorbidities. The risk of developing ETD can be reduced by implementing prompt treatment for SDB. Multidisciplinary evaluation including ETD should be conducted in the management of patients presenting with SDB.

Objective. Autologous fat injection laryngoplasty is ineffective for some patients with iatrogenic vocal fold paralysis, and additional laryngeal framework surgery is often required. An acoustically measurable outcome predictor for lipoinjection laryngoplasty would assist phonosurgeons in formulating treatment strategies. Methods. Seventeen thyroid surgery patients with unilateral vocal fold paralysis participated in this study. All subjects underwent lipoinjection laryngoplasty to treat postsurgery vocal hoarseness. After treatment, patients were assigned to success and failure groups on the basis of voice improvement. Linear prediction analysis was used to construct a new voice quality indicator, the number of irregular peaks (NIrrP). It compared with the measures used in the Multi-Dimensional Voice Program (MDVP), such as jitter (frequency perturbation) and shimmer (perturbation of amplitude). Results. By comparing the [i] vowel produced by patients before the lipoinjection laryngoplasty (AUC = 0.98, 95% CI = 0.78-0.99), NIrrP was shown to be a more accurate predictor of long-term surgical outcomes than jitter (AUC = 0.73, 95% CI = 0.47-0.91) and shimmer (AUC = 0.63, 95% CI = 0.37-0.85), as identified by the receiver operating characteristic curve. Conclusions. NIrrP measured using the LP model could be a more accurate outcome predictor than the parameters used in the MDVP., Competing Interests: There are no competing interests.

Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP.

Background/aim: Organ-preservation treatment for hypopharyngeal cancer has recently become a popular treatment option. However, the severe complications and poor quality of life after non-surgical treatment should be avoided. We accessed the laryngeal or pharyngeal dysfunction-related complications after concurrent chemoradiotherapy (CCRT) as the primary treatment for hypopharyngeal cancer., Patients and Methods: Data concerning all patients treated for hypopharyngeal cancer with primary non-surgical treatment at the China Medical University Hospital from 2002 to 2012 were retrospectively reviewed., Results: A total of 161 patients were included with a median age of 56.6 years. The disease control rates (disease-free >12 months) and severe complication rates were correlated to the tumor (T) stage and nodal (N) stage. In the successful treatment group, the complication rate was related to the N stage. The overall pharyngeal dysfunction, laryngeal dysfunction and aspiration rates were 36%, 27% and 25%, respectively. For patients with T4a disease, hyoid bone invasion significantly increased the severe complication rate (p=0.0212)., Conclusion: The treatment outcome was correlated to the T and N stage. A higher rate of laryngopharyngeal dysfunction occurred when treating hyoid bone invasion in T4a patients with primary non-surgical treatment. In advanced stage, but still resectable hypopharyngeal tumors, the poorer quality of life due to non-function larynx was noted after treating with CCRT., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Oral squamous cell carcinoma (OSCC) constitutes >90% of oral cancers and is the sixth most common malignancy among males worldwide and the fourth leading cause of death due to cancer among males in Taiwan. However, most patients do not receive a diagnosis of OSCC until the late stages, which have a lower survival rate. The use of molecular marker analysis to identify early-stage OSCC would permit optimal timing for treatments and consequently prolong survival. The aim of this study was to identify biomarkers of OSCC using the Illumina GoldenGate Methylation Cancer Panel, which comprised a total of 1,505 CpG sites covering 807 genes. Samples of buccal mucosa resected from 40 OSCC patients and normal tissue samples obtained from 15 patients (normal mucosa from OSCC patients or from patients undergoing surgery unrelated to OSCC) were analyzed. Fms-related tyrosine kinase 4 (FLT4) methylation exhibited a perfect specificity for detecting OSCC, with an area under the receiver operating characteristic curve of 0.91 for both all-stage and early-stage OSCC. Methylation of 7 genes (ASCL1, FGF3, FLT4, GAS7, KDR, TERT, and TFPI2) constitutes the top-20 panels for detecting OSCC. The top-20 panels for detecting early-stage OSCC contain 8 genes: ADCYAP1, EPHA7, FLT4, GSTM2, KDR, MT1A, NPY, and TFPI2. FLT4 RNA expression and methylation level were validated using RT-PCR and a pyrosequencing methylation assay. The median level of FLT4 expression was 2.14-fold for normal relative to OSCC tissue samples (P < 0.0001). Among the 8 pyrosequenced FLT4 CpG sites, methylation level was much higher in the OSCC samples. In conclusion, methylation statuses of selected genes, and especially FLT4, KDR, and TFPI2, might be of great potential as biomarkers for early detection of buccal OSCC.

Sialolipoma is a rare benign neoplasm and was recently described as a histological variant of intraoral lipoma. In the current report, the case of a of a 65-year-old female with a slow-growing mass in the right parotid gland with recurrence is presented. The initial clinical diagnosis was a benign salivary gland tumor. The tumor was situated between the right parotid gland and the right masseter muscle; therefore, a superficial parotidectomy was performed. Histopathology revealed that the tumor was a sialolipoma of the parotid gland. During the three-month follow-up, a recurrent right parotid tumor was identified in the deep lobe space of the right parotid gland and a deep lobe parotidectomy was performed. The present case demonstrates that although surgical excision is generally sufficient to treat parotid gland sialolipoma, postoperative follow-up is required as multifocal lesions may potentially remain, which could result in recurrence.

The innate immune system is the first line in the defense system and prevents the body from further bacteria, virus, or fungal infections. Most of the innate immune system is relevant to mucosa immunity. Lactotransferrin is secreted from the human mammal breast duct epithelial tissue and strengthens infant immunity to defense with regard to outward pathogens. Splunc-1 is also an innate material secreted from the soft palate, lung, nasal cavity epithelium, and mucosa. It helps with mucosa defense against bacterial, virus, and even fungus. LPS is the main etiology of Gram-negative bacilla infection source. And studies of lactoferricin and slpunc-1 both can combine with LPS and subsequently cause insults to the mucosa. Although, we know that both of them partake in an important role in innate immunity, we do not know the effects when they work together. In this study, we just overview silicon stimulation to examine the combination of Lactoferricin and Splunc-1 and the effect with regard to LPS.

Objectives: To describe an extremely rare pediatric sinonasal schwannoma, and to reviewmanagement strategies and relevant literature., Methods: Case report of pediatric sinonasal schwannoma, that was imaged with computed tomography and magnetic resonance imaging and managed endoscopically. Immunohistochemical analysis was performed to determine pathology., Results: A 12-year-old girl presented with a 2-month history of progressive left exophthalmos. Imaging studies showed a large heterogeneous tumour arising from the ethmoid sinus and extending to the base of the skull and to the orbital cavity. The lesion was removed with an endonasal radical excision. The final pathological diagnosis was schwannoma. There was no tumour recurrence or any major complication during the 2-year follow up., Conclusion: Schwannoma should be considered in the differential diagnosis for pediatric patients with intranasal masses. Depending on the location and extent of the tumour, endonasal endoscopic excision could be a suitable management strategy.

The recurrent sinonasal inverted papilloma (IP) could be transformed to sinonasal squamous cell carcinoma. We use protein expression patterns by immunohistochemical method to see whether the expression of p53, p16, p21, and p27 belongs to cell-cycle-regulators and PCNA (proliferating cell nuclear antigen) and Ki-67 the proliferation markers in sixty patients with sinonasal inverted papilloma, and 10 of them with squamous cell carcinoma transformation. Significantly elevated levels of Ki-67, p27, and PCNA in IP with squamous cell carcinoma transformation of sinonasal tract compared with inverted papilloma were revealed. No variation of p16, p21, PLUNC (palate, lung, and nasal epithelium clone protein) and p53 expression was correlated to sinonasal IP malignant transformation by multivariate survey. However, we found elevated PLUNC expression in IPs with multiple recurrences. Finally, we found that PCNA, p27 may interact with CDK1 which promote IP cell proliferation and correlate to sinonasal squamous cell carcinoma. Ki-67 could work throughout the cell cycles to cause malignant transformation. In conclusion, this is a first study showing the correlation of Ki-67, PCNA interacted with CDK1 might lead to malignant transformation. Elevated PLUNC expression in the sinonasal IPs was related to multiple recurrences in human.