Effect of Age and Gender on Taste Function as Measured by the Waterless Empirical Taste Test.

The effect of age and gender on taste function is rarely investigated. Therefore, we tried to study the effect of age and gender on taste function as evaluated by the Waterless Empirical Taste Test (WETT®). The WETT® consists of 40 strips that are coated with one of five tastants (sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate). Each tastant is prepared with four different concentrations. These 40 strips are interspersed with an additional 13 tasteless strips. To implement the WETT®, a strip was placed on the middle portion of the tongue. The subjects closed their mouth and tasted the strip. They then chose one of six answers (sweet, sour, salty, bitter, brothy, or no taste at all). If the answer was correct, one score was acquired. One-hundred-and-twenty healthy men and women were collected in this study. Among them, there were 40 subjects in each age group of 20-39 years, 40-59 years, and ≥60 years. The overall taste and individual tastant function decreased with age, particularly between subjects aged 20-39 years and those aged ≥60 years. The overall taste and individual tastant function were better in females than in males, especially for subjects aged older than 59 years. Our results show that taste function is affected by both age and gender.

Risk Prediction of Chronic Rhinosinusitis with or without Nasal Polyps in Taiwanese Population Using Polygenic Risk Score for Nasal Polyps.

The association between single nucleotide polymorphisms and chronic rhinosinusitis (CRS) has been determined. However, it was not known whether the polygenic risk score (PRS) for nasal polyps (NP) could predict CRS with NP (CRSwNP) or without NP (CRSsNP). The aim of this study was to investigate the association between PRSs for NP and the risk of CRS with or without NP. Data from 535 individuals with CRS and 5350 control subjects in the Taiwan Precision Medicine Initiative project were collected. Four PRSs for NP, including PGS000933, PGS000934, PGS001848, and PGS002060 from UK Biobank, were tested in these participants. They were divided into four groups according to quartiles of PRSs. The logistic regression model was performed to evaluate CRSwNP and CRSsNP risk according to PRSs for NP. The PGS002060 had the highest area under the curve at 0.534 for CRSsNP prediction and at 0.588 for CRSwNP prediction. Compared to subjects in the lowest PRS category, the PGS002060 significantly increased the odds for CRSsNP by 1.48 at the highest quintile (p = 0.003) and by 2.32 at the highest quintile for CRSwNP (p = 0.002). In addition, the odds for CRSwNP increased by 3.01 times in female CRSwNP patients (p = 0.009) at the highest quintile compared with those in the lowest PRS category. The PRSs for NP developed from European populations could be applied to the Taiwanese population to predict CRS risk, especially for female CRSwNP.

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

Influence of Age and Gender on Nasal Airway Patency as Measured by Active Anterior Rhinomanometry and Acoustic Rhinometry.

In this study, we aimed to investigate the influences of age and gender on nasal airway patency, as measured by both active anterior rhinomanometry (AAR) and acoustic rhinometry (AR). The nasal airway patency of healthy subjects was evaluated using AAR and AR. In AAR, the subjects generated airflow actively through inspiration and expiration in repetitions of 10, while nasal patency was measured at an inspiratory and expiratory reference pressure of 75 Pa. In AR, we assessed the geometry of the nasal cavity through the analysis of sound waves reflected from the nasal cavities in order to measure both cross-sectional areas and nasal volumes. The subjects were divided by gender, with all males and females then grouped by ages of 20-39 years, 40-59 years and ≥60 years. There were 40 subjects in each group. The mean resistance measured by AAR and the cross-sectional areas and nasal volumes measured by AR were not different between the different age groups; however, the cross-sectional areas and nasal volumes were found to be lesser in females than in males. Our results showed that nasal airway patency was not affected by age, while females were shown to have wider nasal passages than males.

The Effect of Chinese Herbal Medicine on Traumatic Anosmia: A Prospective, Randomized Clinical Trial.

OBJECTIVE: Chinese herbal medicine (CHM) has been implemented as a form of treatment for olfactory dysfunction. In this study, we aimed to use a tailored Guizhi decoction for the treatment of traumatic olfactory dysfunction. METHODS: Patients who had lost olfactory function after experiencing head trauma and whose olfactory function was anosmic were selected. The eligible patients were randomly assigned to two groups. In the CHM group, a tailored Guizhi decoction was prescribed, with patients also undergoing olfactory training (OT). In the OT group, patients performed OT only. The olfactory function of each patient was evaluated by both the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (TC-UPSIT), at both 3 and 6 months after the completion of treatment. RESULTS: A total of 38 patients in the CHM group and 40 in the OT group completed the study. The TC-UPSIT scores of patients slightly rose after treatment in both the CHM and OT groups. Nevertheless, there were no significant differences in TC-UPSIT scores before and after treatment in both groups. However, the PEA thresholds improved significantly in both CHM and OT groups (p = 0.005 and 0.016, respectively). Of note, there were no significant differences in threshold or identification scores between the CHM and OT groups. CONCLUSION: Our results show that adding a tailored Guizhi decoction to OT conferred a limited benefit to the olfactory function of patients experiencing traumatic anosmia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:1473-1479, 2023.

Comparison of Bacteriology Between Eosinophilic and Noneosinophilic Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVE: To compare culture results between eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) and noneosinophilic CRS with nasal polyps (nECRSwNP). STUDY DESIGN: Retrospective study. SETTING: Tertiary medical center. METHODS: We retrospectively analyzed a cohort of CRSwNP patients undergoing primary functional endoscopic sinus surgery. Prior to surgery, swab samples for bacterial culture were collected from their middle meatus using cotton tips. After surgery, postoperative specimens were histologically examined for tissue eosinophilia. A tissue eosinophil density of >10 cells at high power magnification was used to discriminate between ECRSwNP and nECRSwNP. RESULTS: A total of 295 patients were studied with polyps present on 471 sides of the nasal cavity. Among them, 236 sides were ECRSwNP, and the remaining 235 sides were nECRSwNP. Bacterial growth was found in 94 ECRSwNP sides, and in 88 nECRSwNP sides. Culture rates were similar between ECRSwNP and nECRSwNP sides (p = .595). However, Gram-negative aerobes were found in 25 of 236 ECRSwNP sides, and in 42 of 235 nECRSwNP sides. The Gram-negative culture rate was significantly higher in nECRSwNP than in ECRSwNP sides (p = .024). CONCLUSION: The bacteriology of CRS was different between ECRSwNP and nECRSwNP. The Gram-negative aerobes were present more in nECRSwNP than in ECRSwNP.

Comparison of mycology between different types of chronic rhinosinusitis.

BACKGROUND: The aim of this study was to culture fungi from the nasal discharge of patients with chronic rhinosinusitis (CRS) using both a traditional and Ponikau et al's method, and subsequently compare the culture results between CRS with nasal polyps (CRSwNPs) and without nasal polyps (CRSsNPs), and between eosinophilic and noneosinophilic CRS. METHODS: Eighty-one CRS patients with CRS who underwent functional endoscopic sinus surgery were enrolled. Before surgery, the severity of each patient's CRS was evaluated through an endoscopic examination and CT scan. Swab samples were collected from the middle meatus for traditional fungal cultures using cotton-tipped sticks. Afterward, the ipsilateral nasal cavity was irrigated, with the irrigated fluid processed using Ponikau et al's method for fungal culture. RESULTS: The endoscopic and CT scores were significantly higher in CRSwNPs than CRSsNPs, but were not different between eosinophilic CRS and noneosinophilic CRS. Using Ponikau et al's method, 61/81 (75.3%) of the specimens grew fungi. Among them, 20 of 32 (62.5%) CRSwNPs specimens and 41 of 49 (83.7%) CRSsNPs specimens grew fungi. For eosinophilic CRS specimens, 35 of 46 (76.1%) grew fungi, and 26 of 35 (74.3%) noneosinophilic CRS specimens grew fungi. The fungal culture rate was borderline significantly higher in CRSsNPs than CRSwNPs ( p = 0.058) but was not significantly different between eosinophilic CRS and noneosinophilic CRS ( p = 1). However, Cladosporium was significantly more common in CRSsNPs than CRSwNPs ( p = 0.048). CONCLUSION: Our results showed that the mycology of CRS was different between CRSwNPs and CRSsNPs.

Effect of Functional Endoscopic Sinus Surgery on Gustatory Function in Patients With Chronic Rhinosinusitis.

OBJECTIVES: In this study, we investigated the effect of functional endoscopic sinus surgery (FESS) on gustatory function in patients with chronic rhinosinusitis (CRS). METHODS: Forty-three patients with CRS who underwent FESS were included in this study. Prior to FESS and 3 months after surgery, the severity of rhinosinusitis was assessed using the Taiwanese version of the 22-item SNOT (SNOT-22), endoscopic examination, and acoustic rhinometry. The olfactory function was evaluated using the phenylethyl alcohol odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test, and the gustatory function was evaluated using the whole mouth suprathreshold taste test (WMTT) and the taste quad test (TQT). Subgroup analyses were performed based on CRS phenotypes and endotypes. RESULTS: The SNOT-22 significantly improved 3 months after FESS for all patients with CRS. The endoscopic score and olfactory function significantly improved in patients with eosinophilic CRS and in patients with nasal polyps (CRSwNP). The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in patients without nasal polyps. In addition, patients with noneosinophilic CRS had significantly decreased WMTT and salty scores 3 months after FESS. CONCLUSION: Our results showed that the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammatory patterns.

Nasal Mycology of Chronic Rhinosinusitis Revealed by Nanopore Sequencing.

BACKGROUND: Nanopore sequencing (NS) is a third-generation sequencing technology capable of generating reads of long sequences. In this study, we used NS to investigate nasal mycology in patients with chronic rhinosinusitis (CRS). METHODS: Nasal cavities of 13 CRS patients were individually irrigated with 20 mL of distilled water. The irrigant was forcefully blown by the patient into a basin. The collected fluid was placed into a centrifuge tube and processed using the method of Ponikau et al. The collected specimens were used for traditional fungal culture and sequenced for total DNA using NS. RESULTS: Traditional fungal culture successfully grew fungi in the specimens of 11 (84.6%) patients. Aspergillus sp. and Penicillium sp. were found in four (30.8%) patients, Cladosporium sp. in three (23.1%) patients, and Candida albicans, Mucor sp. and Chaetomium sp. in one patient. NS revealed fungi abundance ranged from 81 to 2226, with the Shannon species diversity ranging from 1.094 to 1.683 at the genus level. Malassezia sp. was sequenced in 13 patients, Aspergillus sp. in 12 (92.3%) patients, Candida albicans in 11 (84.6%) patients, and Penicillium sp. in 10 (76.9%) patients. CONCLUSION: Our results showed that NS was sensitive and fast in detecting nasal fungi in CRS patients.

Influence of COVID-19 pandemic on the decision making of patients in undergoing gamma knife radiosurgery.

PURPOSE: Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery. METHODS: From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up. RESULTS: Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p < 0.001, and p < 0.001, respectively). The fewer OPD visits and MRI examinations also showed the same trends. High proportion of neurological deficits were found in the pandemic group (65.4%) compared with the control (45.4%) or vaccination group (58.1%) (p < 0.001). The Charlson comorbidity in the pandemic group was 3.9 ± 3.3, the control group was 4.6 ± 3.2, and the vaccination group was 3.1 ± 3.1. There were similar inter-group difference (p < 0.001). In multiple variant analyses, longer time intervals from the diagnosis to consultation or treatment, OPD frequency and MRI examination were likely influenced by the status of the COVID-19 pandemic as they were alleviated by the vaccination. CONCLUSIONS: The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic.

Validation of the clinical applicability of the brief self-administered waterless empirical taste test during the era of COVID-19.

BACKGROUND: This study was performed to test the clinical applicability of a new taste test, the Brief Self-Administered Waterless Empirical Taste Test (B-WETT) in the era of COVID-19. METHODS: Sixty healthy volunteers and 60 patients experiencing gustatory dysfunction were enrolled. All subjects received both the Self-Administered WETT and the new B-WETT which are comprised of disposable plastic strips containing sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate tastants to evaluate taste function. The healthy volunteers were re-tested with the WETT and B-WETT after an inter-test interval of at least 7 days to measure retest reliability. RESULTS: The sum scores of five tastants of the first test were 25.7 for males and 29.5 for females in WETT, and 12.4 for males and 15.2 for females in B-WETT. There were significant differences in the sum scores between males and females whether in WETT or B-WETT. The sum scores strongly correlated between WETT and B-WETT, whether in healthy volunteers or in patients with gustatory dysfunction (r >0.7). There was also a strong correlation between the first and second tests of B-WETT for the sum scores. CONCLUSION: This study shows that B-WETT is a valid and reliable taste test, and is convenient for use in the era of COVID-19 to evaluate the taste function of patients.

Laboratory Surge Response to the COVID-19 Pandemic: An Incident Command System Approach.

The COVID-19 pandemic has reaffirmed the critical significance of effective diagnostics in outbreak response. In Taiwan, the COVID-19 wave in May 2021 led to a rapidly growing demand for SARS-CoV-2 diagnostic tests. To meet the challenge, an extensive system-wide emergency preparedness plan, hospital emergency incident command system (HEICS), was developed to deal with emergencies involving healthcare systems. During the wave of the COVID-19 outbreak, a 19.4-fold increase in SARS-CoV-2 PCR (polymerase chain reaction) diagnostic tests occurred in the hospital. The incident commander of TCVGH reviewed COVID-19 related events daily and purchased a high-throughput PCR machine for SARS-CoV-2 PCR diagnostic tests. In addition, the Department of Operations was responsible for staff scheduling and educational training. The turn-around times of SARS-CoV-2 diagnostic tests were shortened from 21.2 hours to 5.8 hours in the second week of the COVID-19 wave. Implementation of HEICS integrated resources could be helpful for expanding surge capacity during future outbreaks.

Maintenance metronomic chemotherapy for metastatic/recurrent nasopharyngeal carcinoma.

BACKGROUND: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). METHODS: Ninety-eight patients with met/rec NPC were first salvaged by IV cisplatin-based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. RESULTS: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression-free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. CONCLUSION: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression-free survivals while demonstrating low toxicity in patients with met/rec NPC.

Validation of the local applicability of the 'TIB' Olfactory Test Device in the era of COVID-19.

OBJECTIVE: To evaluate the validity and test-retest reliability of the novel 'TIB' Olfactory Test Device (TIB) and to determine its normative values. METHODS: The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis. RESULTS: This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests (r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects. CONCLUSION: The validity and test-retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

Effect of hypochlorous acid nasal spray as an adjuvant therapy after functional endoscopic sinus surgery.

OBJECTIVES: To evaluate the efficacy of hypochlorous acid (HOCl) nasal spray as an adjuvant therapy after functional endoscopic sinus surgery (FESS). MATERIAL AND METHODS: Patients with chronic rhinosinusitis who had received FESS for treatment were recruited and assigned to one of two groups at random at one month post-surgery. In the HOCl group, patients received 0.02% HOCl nasal spray three times a day for two months. In the control group, normal saline (NS) nasal irrigation was given. Before FESS and before and after nasal spray or irrigation, patients completed the Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22). In addition, patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial cultures obtained from their middle meatus. RESULTS: Seventy-eight patients completed the study. Among them, 41 received HOCl nasal spray, and 37 received NS irrigation. Endoscopic score significantly decreased after 2-month HOCl nasal spray (p = 0.036). TWSNOT-22 score also decreased, although insignificantly (p = 0.285). In contrast, TWSNOT-22 score significantly decreased after NS nasal irrigation (p = 0.017), but endoscopic score did not significantly decrease (p = 0.142). CONCLUSIONS: Our results showed that HOCl nasal spray had a similar effect to that of NS nasal irrigation in post-FESS care. It can be an alternative of NS nasal irrigation for its convenient application.

A Pilot Study of the Waterless Empirical Taste Test.

OBJECTIVES: This study was performed to test the clinical applicability of a new taste test-the waterless empirical taste test (WETT). METHODS: Sixty healthy volunteers and 20 patients with oral cancer were enrolled. They all received the conventional solution-based whole-mouth suprathreshold taste test (WMTT), which contained sucrose, citric acid, sodium chloride, and caffeine solutions for tastants, along with the WETT. The WETT used plastic strips to deliver tastants. The strip was embedded with sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate taste enhancer in 4 different concentrations. Each strip was tested twice. Thirty of the healthy volunteers received the WETT again to measure a retest reliability. Case-control matching by age and gender was used to compare the scores of WMTT and WETT between 13 healthy volunteers and 13 patients with oral cancer. RESULTS: The correlation was not high between the WMTT and WETT (r < 0.7) whether in the healthy volunteers or in patients with oral cancer. In terms of retest reliability of the WETT, the mean total score was 24.9 ± 7.3 for the first test and 25.8 ± 8.4 for the second test. The intraclass correlation coefficient was 0.85 (P < .001). When case-control matching was performed, the WMTT scores were not significantly different between 13 healthy volunteers and 13 patients with oral cancer (P = .266), but the WETT scores were significantly lower in patients with oral cancer (P = .017). CONCLUSION: This study showed that the results of the WETT were not highly correlated with those of the WMTT. However, its retest reliability was high, and its results were significantly different between the healthy volunteers and the patients with oral cancer.

Less Is More? The Association between Survival and Follow-Up Protocol after Treatment in Oral Cavity Cancer Patients from a Betel Quid-Prevalent Region.

The optimal follow-up protocol after treatment of oral cavity cancer patients is still debatable. We aimed to investigate the impact of frequency of different imaging studies and follow-up visits on the survival of oral cavity cancer patients. The current study retrospectively reviewed oral cavity cancer patients who underwent surgical intervention in our hospital. Basic demographic data, tumor-related features, treatment modalities, imaging studies, and clinic visits were recorded. Cox proportional hazard model was used to examine the influence of variables on the survival of oral cavity cancer patients. In total, 741 patients with newly diagnosed oral cavity cancer were included in the final analysis. Overall, the frequency of imaging studies was not associated with survival in the multivariate analysis, except PET scan (hazard ratio [HR]: 5.30, 95% confidence interval [CI]: 3.57-7.86). However, in late-stage and elder patients, frequent head and neck CT/MRI scan was associated with a better prognosis (HR: 0.55, 95% CI: 0.36-0.84; HR: 0.52, 95% CI: 0.30-0.91, respectively). In conclusion, precision medicine is a global trend nowadays. Different subgroups may need different follow-up protocols. Further prospective study is warranted to clarify the relationship between frequency of image studies and survival of oral cavity cancer patients.

A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population.

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression.

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.