Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD. METHODS: In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6 months. Clinical parameters (e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6 months after starting dupilumab therapy. RESULTS: Of the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6 months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: -2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6. CONCLUSION: In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

Retronasal olfactory testing in early diagnosed and suspected COVID-19 patients: a 7-week follow-up study.

OBJECTIVES: Olfactory dysfunction (OD) constitutes a major symptom in Coronavirus Disease 2019 (COVID-19). Yet, most data on smell loss rely on the evaluation of orthonasal olfactory performance. Therefore, we aimed to assess retronasal olfactory function (ROF) over a period of several weeks in proven and suspected COVID-19 patients. METHODS: One hundred and one subjects with suspected or laboratory-proven COVID-19 participated in this study. In patients with OD no longer than 4 weeks after initial symptom onset, ROF was measured with the 7-item Candy Smell Test ten times over 7 weeks. RESULTS: Olfactory function was decreased in the investigated patients and remained decreased over the course of 7 weeks. One-way repeated-measures ANOVA revealed no significant difference of ROF between different measurement time points. However, self-assessment of smell and flavour improved significantly (p = 0.013 and p = 0.043), but did not show complete recovery. CONCLUSION: The current investigation revealed significant improvements in subjective smell and flavour perception over the course of 7 weeks in proven and suspected COVID-19 patients suffering from acute OD. However, objectively measured ROF based on a screening test revealed no improvements within the same time period.

Decrease and Recovery of Olfactory and Gustatory Function in a Case of SARS-CoV-2 Infection.

Self-reported chemosensory dysfunction in severe acute respiratory syndrome coronavirus 2 patients is common. We present a case of reversible smell loss in a young patient with mild coronavirus disease 2019 infection assessed with established testing methods over a period of 8 weeks.

Winter peaks in web-based public inquiry into epistaxis.

PURPOSE: Epistaxis represents the most frequent ear, nose, throat-related emergency symptom. Seasonal variation in epistaxis incidence, with peaks during winter months, is widely accepted, although the literature itself remains inconclusive. The objective of this study was to evaluate public inquiry into nose bleeding, by considering Google-based search query frequency on "Epistaxis"-related search terms and to assess possible seasonal variations globally. METHODS: Epistaxis-related search terms were systematically collected and compared using Google Trends (GT). Relative search volumes for the most relevant epistaxis-related terms, covering a timeframe from 2004 to 2019 were analysed using cosinor time series analysis for the United States of America, Germany, the United Kingdom, Italy, Canada, Australia, and New Zealand. RESULTS: Graphical representation revealed seasonal variations with peaks during winter months in the majority of countries included. Subsequent cosinor analysis revealed these variations to be significant (all p < 0.001). CONCLUSION: Public interest in seeking epistaxis-related information through the Internet displayed seasonal patterns in countries from both hemispheres, with the highest interest during winter months. Further studies exploring causality with environmental factors are warranted.

Real-Life Study of Patient Preference for Dupilumab or Revision Surgery for Recurrent Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high rate of recurrence in patients, despite therapy with local corticosteroids and functional endoscopic sinus surgery. Dupilumab, a recombinant monoclonal human IgG4 antibody directed against the IL-4 receptor α that inhibits both IL-4 and IL-13 signal transduction, is available for symptomatic therapy. Patient preference between repeated surgery and injection therapy with Dupilumab is not known. (2) Methods: Patients who had experienced at least one surgical intervention for nasal polyps and were treated with Dupilumab for at least 3 months completed a retrospective patient questionnaire. (3) Results: In a cohort of 75 previously operated CRSwNP patients, 91.5% preferred therapy with Dupilumab to repeated surgery for nasal polyps. Preference for Dupilumab in the subgroups of patients with concomitant Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease (N-ERD) (n = 32), patients with concomitant asthma (n = 25), and patients without concomitant disease (n = 18) was 100%, 96%, and 72%, respectively. (4) Conclusions: Patient preference for Dupilumab over repeat surgery is strongest in previously operated CRSwNP patients with concomitant asthma or N-ERD, but remains very high in patients without concomitant disease.

Seasonal Variations in Public Inquiries into Laryngitis: An Infodemiology Study.

OBJECTIVES: Acute laryngitis is a common disease with self-limiting nature. Since the leading cause is attributed to viral infections and thus self-limiting, many affected individuals do not seek professional medical help. However, because the major symptom of hoarseness imposes a substantial burden in everyday life, it might be speculated that web-based search interest on this condition follows incidence rates, with highest peaks during winter months. The aim of this study was to evaluate global public health-information seeking behaviour on laryngitis-related search terms. METHODS: We utilized Google Trends to assess country-specific, representative laryngitis-related search terms for English and non-English speaking countries of both hemispheres. Extracted time series data from Australia, Brazil, Canada, Germany, the United Kingdom, and the United States of America, covering a timeframe between 2004 and 2019 were first assessed for reliability, followed by seasonality analysis using the cosinor model. RESULTS: Direct comparisons revealed different, representative laryngitis-related search terms for English- and non-English speaking countries. Extracted data showed a trend of higher reliability in countries with more inhabitants. Subsequent graphical analysis revealed winter peaks in all countries from both hemispheres. Cosinor analysis confirmed these seasonal variations to be significant (all P < 0.001). CONCLUSION: Public interest in laryngitis-related, online health information displayed seasonal variations in countries from both hemispheres, with highest interest during winter months. These findings emphasize the importance to optimize the distribution of reliable, web-based health education in order to prevent the spread of misinformation and to improve health literacy among general populations.

Changes in Acoustic Aspects of Vocal Function in Children After Adenotonsillectomy.

BACKGROUND: Adenotonsillectomy is one of the most common pediatric surgical procedures. Postoperative voice changes are a very common concern among patient's parents. Therefore, the aim of this study is to analyze acoustic voice parameters after adenotonsillectomy, tonsillectomy, and adenoidectomy in pediatric patients in a tertiary referral academic center. PATIENTS AND METHODS: All pediatric patients undergoing an adenotonsillectomy, tonsillectomy or adenoidectomy in a single center from 2002 to 2018 were included in the study. Change of fundamental frequency, jitter, shimmer, and harmonic-noise ratio at first, seventh and 30th postoperative day compared to preoperative values were the primary outcome parameters. Statistical analysis was performed using repeated measures analysis of variance model. RESULTS: A total of 1258 patients were included in the study. The mean age of patients at the time of surgery was 8.3 years (range 3.0-18.0 years). Around 698 were male (55.5%) and 560 female (44.5%). The values of fundamental frequency increased significantly after the first and seventh postoperative day (P = 0.001 both) but normalized 1 month after surgery (P = 0.962). At the first postoperative month, values of jitter and shimmer decreased significantly (P = 0.005 and P = 0.002, respectively). Measurements of harmonic-noise ratio revealed a significant increase 30 days after surgery (P = 0.004). CONCLUSION: Statistically significant differences in objective voice parameters within the first postoperative month after tonsillectomy, adenoidectomy, and adenotonsillectomy were observed. The fundamental frequency returned to normal 1 month after surgery. These findings can contribute in soothing the concerns of parents regarding postoperative voice changes.

High Prevalence of MYO6 Variants in an Austrian Patient Cohort With Autosomal Dominant Hereditary Hearing Loss.

INTRODUCTION: Genetic hearing loss (HL) is often monogenic. Whereas more than half of autosomal recessive (AR) cases in Austria are caused by mutations in a single gene, no disproportionately frequent contributing genetic factor has been identified in cases of autosomal dominant (AD) HL. The genetic characterization of HL continues to improve diagnosis, genetic counseling, and lays a foundation for the development of personalized medicine approaches. METHODS: Diagnostic HL panel screening was performed in an Austrian multiplex family with AD HL, and segregation was tested with polymerase chain reaction and Sanger sequencing. In an independent approach, 18 unrelated patients with AD HL were screened for causative variants in all known HL genes to date and segregation was tested if additional family members were available. The pathogenicity of novel variants was assessed based on previous literature and bioinformatic tools such as prediction software and protein modeling. RESULTS: In six of the 19 families under study, candidate pathogenic variants were identified in MYO6, including three novel variants (p.Gln441Pro, p.Ser612Tyr, and p.Gln650ValfsTer7). Some patients carried more than one likely pathogenic variant in known deafness genes. CONCLUSION: These results suggest a potential high prevalence of MYO6 variants in Austrian cases of AD HL. The presence of multiple rare HL variants in some patients highlights the relevance of considering multiple-hit diagnoses for genetic counseling and targeted therapy design.

The association between COVID-19 cases and deaths and web-based public inquiries.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) emerged in December 2019 and rapidly spread globally. Since there is still no specific treatment available, prevention of disease spread is crucial to manage the pandemic. Adequate public information is very important. To assess the optimal timing, the aim of this study was to investigate the association between web-based interest and new cases and deaths due to COVID-19. METHODS: Web-based interest for queries related to 'coronavirus' was assessed between 1 January and 19 June 2020, using Google Trends in Australia, Brazil, Canada, Germany, Italy, South Africa, South Korea, Spain, United Kingdom, and the United States of America. Reliability analysis of the used search terms was performed using the intraclass correlation coefficient. To investigate the association between web-based interest and new COVID-19 cases or deaths, the relative search volume was analysed for correlation with new cases and deaths. RESULTS: Reliability analysis revealed excellent reliability for COVID-19 search terms in all countries. Web-based interest peaked between 23 February and 5 April 2020, which was prior to the peak of new infections and deaths in most included countries. There was a moderate to strong correlation between COVID-19 related queries and new cases or new deaths. CONCLUSION: Web-based interest in COVID-19 peaked prior to the peak of new infections and deaths in most countries included. Thus, monitoring public interest via Google Trends might be useful to select the optimal-timing of web-based disease-specific information and preventive measures.

PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis.

Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan-Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.

Retronasal olfactory function in patients with smell loss but subjectively normal flavor perception.

OBJECTIVES: The human sense of smell constitutes the main part of flavor perception. Typically, patients with loss of olfactory function complain of diminished perception during eating and drinking. However, some patients with smell loss still report normal enjoyment of foods. The aim of the present study was to compare orthonasal and retronasal olfactory function in patients with non-sinonasal smell loss and subjectively normal flavor perception. METHODS: Nineteen patients (mean age [range] 52.0 [8-83 years]) with self-reported olfactory impairment but subjective normal flavor perception were included. Olfactory performance was assessed using the Sniffin' Sticks (TDI) for orthonasal and the Candy Smell Test (CST) for retronasal function. Visual analogue scales were used for self-assessment of odor (SOP), taste (STP), and flavor perception (SFP), ranging from 0 (no perception) to 10 (excellent perception). RESULTS: Mean (SD) SFP was 8.0 (1.8). Mean (SD) orthonasal TDI-score of all patients was 14.4 (5.3, range 6-25.3) with 11 patients classified as anosmic and eight as hyposmic. Mean/SD retronasal CST-score was 8.8 (2.7, range 3-13) within the range of anosmia/hyposmia. No correlation was found between SFP and the CST (P = .62). CONCLUSION: The present results showed that despite claiming normal flavor perception, our patients were ortho- and retronasally dysosmic using standard tests for olfactory function. Although other explanations could be possible, we suggest that this subjective flavor perception might be due to unconscious memory recall from previously experienced cross-modal sensory interactions. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1629-1633, 2020.

Odor Mixtures in Identification Testing Using Sniffin' Sticks: The SSomix Test.

Clinical tests assessing olfactory performance have become indispensable for diagnosing olfactory dysfunction. As time and personnel resources are limited, it would be advantageous to have shorter protocols focusing on singular aspects of olfactory performance, such as odor identification. However, such a unidimensional approach is often inconclusive and needs further tests (and tools). Hence, new testing methods with high levels of sensitivity, specificity, and reproducibility are required for clinical practice. Here, we developed a Sniffin' Sticks odor mixture identification test method (SSomix), with emphasis on resource efficiency and simplicity of administration. SSomix consists of mixtures of two and three odors applied onto a piece of paper using 11 out of 16 items from the original Sniffin' Sticks identification test kit. A total of 66 healthy subjects and 22 patients with olfactory dysfunction were included in the study. SSomix showed good to excellent test-retest reliability and validity. The area under the receiver operating characteristics curves indicated good diagnostic accuracy in identifying patients with reduced and severely impaired olfactory function. SSomix was a suitable downsizing of the original kit, especially regarding resource efficiency.

Associations between the Quality of Life and Nasal Polyp Size in Patients Suffering from Chronic Rhinosinusitis without Nasal Polyps, with Nasal Polyps or Aspirin-Exacerbated Respiratory Disease.

Chronic rhinosinusitis (CRS) is a common disease that substantially impairs the quality of life (QoL). Here, we aimed to assess patients' QoL in different subtypes of CRS and correlated this with nasal polyp size to improve the clinical understanding of the burden of disease. In this retrospective single-center study, 107 patients with the following diagnoses were analyzed: CRS without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP), or aspirin-exacerbated respiratory disease (AERD). Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) scores and their correlation with endoscopic Total Polyp Scores (TPS) were evaluated. The mean SNOT-20 GAV scores were highest in patients with AERD (AERD = 43.4, CRSwNP = 36.3, CRSsNP = 30.9). A statistically significant correlation of total SNOT-20 GAV score with TPS was observed in CRSwNP patients (r = 0.3398, p = 0.0195), but not in AERD patients (r = 0.2341, p = 0.1407). When analyzing single SNOT-20 parameters, a strong correlation with TPS was observed for blockage/congestion of the nose, particularly in AERD patients (r = 0.65, p < 0.0001). The impact of nasal polyp size on the QoL differs amongst the subgroups of CRS. Nasal symptoms have the greatest impact on QoL in patients suffering from AERD. CRSwNP and AERD patients should be separately analyzed in clinical investigations and interpretations due to significant differences in QoL.

The Sniffin' Sticks Odor Discrimination Memory Test: A Rapid, Easy-to-Use, Reusable Procedure for Testing Olfactory Memory.

OBJECTIVES: Neurodegenerative diseases can alter odor memory in addition to inducing quantitative impairment, and olfactory memory can be tested using the validated olfactory memory test with encapsulated odors (Odor Discrimination Memory Test [ODMT]). The aim of this study was to investigate the new Sniffin' Sticks ODMT (SSODMT), which is comparable with the ODMT. METHODS: The SSODMT was administered to 48 subjects (30 women, 18 men; mean age, 34.6 ± 16.3 years). Olfactory function was assessed using the 16-item Sniffin' Sticks Identification Test. The ODMT was administered to a subgroup of 10 subjects to assess the comparability of the SSODMT and the ODMT. Test-retest reliability was studied in another 20 subjects (10 women, 10 men; mean age, 32.9 ± 16.4 years). RESULTS: The mean SSODMT score was 10.7 ± 1.8 (range, 5-12). SSODMT test scores were significantly correlated with Sniffin' Sticks Identification Test scores (r67 = 0.66, P < .001) and were significantly negatively correlated with subject age (r48 = -0.70, P < .001). SSODMT and ODMT scores were highly and significantly correlated, indicating that the test results were comparable (r10 = 0.75, P < .05). Test-retest analysis revealed a significant correlation (r20 = 0.68, P < .001). CONCLUSIONS: These results demonstrate the usefulness of the new SSODMT and its comparability with the ODMT. The SSODMT is an easy, rapid, and low-cost tool that is suitable for routine use in evaluating odor memory.