David T. Liu

All Publications

• The olfactory diary: Tracking awareness and consciousness of the sense of smell throughout the day. Laryngoscope investigative otolaryngology Liu, D. T., Besser, G., Moser, V., Prem, B., Sharma, G., Ehrgott, M., Renner, B., Mueller, C. A. 2024; 9 (3): e1268

  Abstract

  The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell.In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin' Sticks. All participants received paper diaries designed for a 14-day period, featuring 12 rows representing 12 daily hours and six columns for various daily life aspects. They were instructed to mark their awareness of smell by indicating the relevant row and column in the diary. Following the return of the diaries, a second olfactory test was conducted within the patient group.On average, patients were consciously aware of their sense of smell around 8 times daily, while healthy participants noted it about 6.5 times a day. Both groups primarily focused on their sense of smell during activities related to "eating," followed by considerations in "social life" and "personal hygiene." Interestingly, distinct patterns emerged: patients peaked in awareness at 8 a.m. and 7 p.m., whereas healthy individuals showed peaks at 6 a.m., 12 p.m., and 7 p.m. Despite regular diary use, we observed no improvement in patients' olfactory function or related quality of life.The olfactory diary is a valuable tool unveiling individual smell awareness patterns in patients with smell loss, aiding in counseling and patient management.4.

  View details for DOI 10.1002/lio2.1268

  View details for PubMedID 38803460

  View details for PubMedCentralID PMC11129550

• Changes in management of head and neck malignancies during the COVID-19 pandemic. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale Lein, A., Brkic, F., Liu, D. T., Haas, M., Salkic, A., Ibrisevic, A., Uscuplic, S., Harcinovic, A., Thurner, T., Brkic, F. F. 2024

  Abstract

  Despite multiple studies from high-income countries, reports from low- and middle-income countries on the impact of COVID-19 on head and neck cancer care remain sparse. This study aimed to assess the effects of the COVID-19 pandemic on head and neck cancer patients at a tertiary reference centre in Bosnia and Herzegovina.We included 228 patients with malignant head and neck tumours evaluated and treated between January 1, 2019, and December 31, 2021. Patient demographics, histological characteristics, and treatment modalities were retrospectively obtained and compared between the pre-pandemic period (pre-COVID-19 group) and the period after the implementation of COVID-19 restrictive measures (COVID-19 group).Patients were significantly older during the COVID-19 pandemic. In particular, 63 patients (44.7%) were under 65 and 78 (55.3%) were 65 or older, while in the pre-COVID-19 period, 53 patients (60.9%) were under 65 and 34 (39.1%) were 65 or older (p = 0.017). The pre-COVID-19 and COVID-19 groups did not significantly differ regarding other patient- and tumour characteristics, or primary treatment modalities.During the COVID-19 pandemic, significantly fewer patients were under 65 at the time of initial work-up, potentially reflecting the more enhanced disease-related anxiety of the younger population. Future studies are warranted to address this population's specific educational and psychological needs to ensure appropriate cancer care.

  View details for DOI 10.14639/0392-100X-N2779

  View details for PubMedID 38712519

• Real-Life Study of Patient Preference for Dupilumab or Revision Surgery for Recurrent Chronic Rhinosinusitis with Nasal Polyps JOURNAL OF PERSONALIZED MEDICINE Gangl, K., Liu, D., Bartosik, T., Campion, N., Vyskocil, E., Mueller, C., Knerer, B., Eckl-Dorna, J., Schneider, S. 2024; 14 (4)

  Abstract

  (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.

  View details for DOI 10.3390/jpm14040338

  View details for Web of Science ID 001210275700001

  View details for PubMedID 38672965

  View details for PubMedCentralID PMC11051141

• Is the evolving role of artificial intelligence and chatbots in the field of otolaryngology embracing the future? European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Chiesa-Estomba, C. M., Speth, M. M., Mayo-Yanez, M., Liu, D. T., Maniaci, A., Borsetto, D. 2024; 281 (4): 2179-2180

  View details for DOI 10.1007/s00405-023-08382-2

  View details for PubMedID 38133807

• Early Results With the New Active Bone-Conduction Hearing Implant: A Systematic Review and Meta-Analysis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Lein, A., Baumgartner, W. D., Riss, D., Gstöttner, W., Landegger, L. D., Liu, D. T., Thurner, T., Vyskocil, E., Brkic, F. F. 2024

  Abstract

  The bone conduction implant (BCI) 602 is a new transcutaneous BCI with smaller dimensions. However, limited patient numbers restrict the statistical power and generalizability of the current studies. The present systematic review and meta-analysis summarize early audiological and medical outcomes of adult and pediatric patients implanted with the BCI 602 due to mixed or conductive hearing loss.Following the Preferred Reporting items for Systematic Reviews and Meta-analyses guidelines, 108 studies were reviewed, and 6 (5.6%) were included in the meta-analysis.The data on study and patient characteristics, surgical outcomes, and audiological test results were extracted from each article. Meta-analysis employed the fixed-effect and random-effects models to analyze the mean differences (MDs) between pre- and postoperative performances.In total, 116 patients were evaluated, including 64 (55%) adult and 52 (45%) pediatric patients. No intraoperative adverse events were reported, while postoperative complications were reported in 2 (3.1%) adult and 2 (3.8%) pediatric patients. Studies consistently showed significant improvements in audiological outcomes, quality of life, and sound localization in the aided condition. In the meta-analysis, we observed a significant difference in the unaided compared to the aided condition in sound field thresholds (n = 112; MD, -27.05 dB; P < 0.01), signal-to-noise ratio (n = 96; MD, -6.35 dB; P < 0.01), and word recognition scores (n = 96; MD, 68.89%; P < 0.01).The implantation of the BCI 602 was associated with minimal surgical complications and excellent audiological outcomes for both the pediatric and the adult cohort. Therefore, our analysis indicates a high level of safety and reliability. Further research should focus on direct comparisons with other BCIs and long-term functional outcomes.

  View details for DOI 10.1002/ohn.728

  View details for PubMedID 38529662

• Presentation Rates for Acute Pharyngitis in the Emergency Room Are Influenced by Extreme Weather Events. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Haas, M., Lucic, M., Pichler, F., Brkic, F. F., Parzefall, T., Riss, D., Liu, D. T. 2024; 170 (3): 795-803

  Abstract

  Extreme weather events are becoming more prevalent with the increasing pace of climate change. These events negatively impact human health and put considerable strain on health care resources, including emergency departments. Within otolaryngology, acute pharyngitis is a common reason for emergency room visits (ERV). Therefore, we aimed to investigate the impact of extreme meteorological conditions on ERV rates related to acute pharyngitis.Retrospective time-series study.ERVs related to acute pharyngitis (n = 1511) were identified at a tertiary care hospital in Vienna, Austria, between 2015 and 2018.The effects of single-day and prolonged (3-day) extreme weather events on ERVs were analyzed using a distributed lag nonlinear model. Relative risk (RR) and cumulative relative risk (cRR) were calculated over a lag period of 14 days. RR refers to the risk for pharyngitis-related ERV at extreme conditions (1st, 5th, 95th, or 99th percentile) compared to the risk at median conditions.Same-day RR (lag0) was elevated more than 3-fold after prolonged extremely low mean temperatures (P = .028). Furthermore, same-day RR after single-day and prolonged extremely high relative humidity was elevated by 51% (P = .024) and 46% (P = .036), respectively. Significant delayed effects on cRR were observed for extreme mean temperatures, relative humidity, and mean wind speeds within 8 days and for extreme atmospheric pressure within 14 days.Extreme weather events impact ERV rates for acute pharyngitis. Extremely low temperatures, high relative humidity, high atmospheric pressure, and low and high wind speeds were risk-promoting factors.

  View details for DOI 10.1002/ohn.581

  View details for PubMedID 37943865

• A scoping review of Rasch analysis and item response theory in otolaryngology: Implications and future possibilities LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Liu, D. T., Mueller, C. A., Sedaghat, A. R. 2024; 9 (1): e1208

  Abstract

  Item response theory (IRT) is a methodological approach to studying the psychometric performance of outcome measures. This study aims to determine and summarize the use of IRT in otolaryngological scientific literature.A systematic search of the Medline, Embase, and the Cochrane Library databases was performed for original English-language published studies indexed up to January 28, 2023, per the following search strategy: ("item response theory" OR "irt" OR "rasch" OR "latent trait theory" OR "modern mental test theory") AND ("ent" OR "otorhinolaryngology" OR "ear" OR "nose" OR "throat" OR "otology" OR "audiology" OR "rhinology" OR "laryngology" OR "neurotology" OR "facial plastic surgery").Fifty-five studies were included in this review. IRT was used across all subspecialties in otolaryngology, and most studies utilizing IRT methodology were published within the last decade. Most studies analyzed polytomous response data, and the most commonly used IRT models were the partial credit and the rating scale model. There was considerable heterogeneity in reporting the main assumptions and results of IRT.IRT is increasingly being used in the otolaryngological scientific literature. In the otolaryngology literature, IRT is most frequently used in the study of patient-reported outcome measures and many different IRT-based methods have been used. Future IRT-based outcome studies, using standardized reporting guidelines, might improve otolaryngology-outcome research sustainably by improving response rates and reducing patient response burden.2.

  View details for DOI 10.1002/lio2.1208

  View details for Web of Science ID 001136988300001

  View details for PubMedID 38362194

  View details for PubMedCentralID PMC10866592

• Impact of the COVID-19 pandemic on management of surgically treated laryngeal squamous cell carcinoma. Biomolecules & biomedicine Lein, A., Liu, D. T., Haas, M., Salkic, A., Ibrisevic, A., Uscuplic, S., Harcinovic, A., Brkic, T., Thurner, T., Brkic, F. F. 2024; 24 (1): 188-195

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the treatment of cancer patients, particularly in terms of treatment choices. This study aimed to assess the effects of the COVID-19 pandemic on the management of surgically treated laryngeal squamous cell carcinoma (LSCC) patients, focusing specifically on changes in treatment modalities. We retrospectively analyzed the data from 102 patients who underwent surgical treatment for LSCC between January 1, 2019, and December 31, 2021, at our tertiary medical center. Patient demographics, histological characteristics, and treatment modalities were extracted from electronic medical records and compared between two time periods: pre-COVID-19 and during COVID-19, marked by the introduction of the hospital entry triage. Of the total patients, 53 (52%) were in the pre-COVID-19 group, and 49 (48%) were in the COVID-19 group. No significant differences in patient characteristics at the initial work-up were observed between the two groups. However, a significant shift in treatment modalities was noted. Fewer patients received postoperative adjuvant therapy in the COVID-19 group (70.5%) compared to the pre-COVID-19 group (95.5%). Importantly, this change did not significantly impact the one-year overall survival (OS) rates. The reduction in the use of postoperative adjuvant therapy during the COVID-19 pandemic may be attributed to efforts to minimize hospital visits due to the risk of COVID-19 infection. Further research is warranted to validate these findings and to investigate the potential effects of such changes in treatment modalities on the long-term survival.

  View details for DOI 10.17305/bb.2023.9481

  View details for PubMedID 37638405

  View details for PubMedCentralID PMC10787613

• Treatment adherence to olfactory training: a real-world observational study RHINOLOGY Haas, M., Raninger, J., Kaiser, J., Mueller, C. A., Liu, D. T. 2024; 62 (1): 35-45

  Abstract

  Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT.In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (>=5.5) and NRS (>=5.5) scores.Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up.Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.

  View details for DOI 10.4193/Rhin23.207

  View details for Web of Science ID 001162986400006

  View details for PubMedID 37838940

• Platelet-to-lymphocyte ratio might predict the response to dupilumab treatment for patients with nasal polyposis. Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale Brkic, F. F., Liu, D. T., Rücklinger, I., Campion, N. J., Bartosik, T. J., Vyskocil, E., Stanek, V., Tu, A., Gangl, K., Schneider, S. 2023; 52 (1): 75

  Abstract

  Dupilumab is a monoclonal antibody against interleukin 4 receptor alpha and has proven to be clinically effective in treating patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, a certain number of patients are non- or partial responders. This study aims to investigate the relevance of inflammatory markers with regard to therapy response to dupilumab in CRSwNP patients.All patients with CRSwNP treated with dupilumab at a tertiary healthcare center with available pretreatment inflammatory markers were included. The values of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with the outcome. Patients were stratified according to the respective median value (> median was considered high). The binary logistic regression was performed with regard to total treatment response (post-treatment total nasal polyp score (NPS) 0).A total of 65 CRSwNP patients with available pretreatment peripheral blood values were included in the study. The mean pre- and post-treatment total NPS values were 4.3 ± 1.9 and 1.2 ± 1.6, respectively. High PLR (> 131.2) was independently associated with a 3.9-fold higher probability of reaching the NPS value of 0 in the multivariable analysis. On the other hand, High NLR (> 1.9) did not significantly associate with the outcome.The current study provides insights into the potential positive predictive value of the high PLR (> 131.2) in CRSwNP patients regarding treatment with dupilumab. There is a need for further prospective studies for validation of these results, especially in cohorts of patients with severe CRSwNP.

  View details for DOI 10.1186/s40463-023-00660-7

  View details for PubMedID 38007429

  View details for PubMedCentralID PMC10676571

• The association between acute otitis externa-related emergency department visits and extreme weather events in a temperate continental climate INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH Nieratschker, M., Haas, M., Lucic, M., Pichler, F., Brkic, F. F., Mueller, C. A., Riss, D., Liu, D. T. 2024; 255

  View details for DOI 10.1016/j.ijheh.2023.114274

  View details for Web of Science ID 001102437000001

• Patient perspectives on recall period and response options in patient-reported outcome measures for chronic rhinosinusitis symptomatology: An international multi-centered study INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Sedaghat, A. R., Derbarsegian, A., Yu, V. T., Alsayed, A., Bitner, B. F., Yeom, B., Liu, D. T., Schneider, S., Adams, S. M., Houssein, F. A., Walters, Z. A., Tripathi, S., Walker, V. L., Singerman, K. W., Meier, J. C., Kim, R., Kuan, E. C., Alsaleh, S., Phillips, K. M. 2024; 14 (5): 898-908

  Abstract

  Existing patient-reported outcome measures (PROMs) for chronic rhinosinusitis (CRS) use a variety of recall periods and response scales to assess CRS symptom burden. Global perspectives of CRS patients regarding optimal recall periods and response scales for CRS PROMs are unknown.This was a multi-center, cross-sectional study recruiting 461 CRS patients from sites across the United States, Saudi Arabia, New Zealand, and Austria. Participants chose which CRS symptom recall period (1 day, 2 weeks, 1 month, >1 month) was most reflective of their current disease state and upon which to best base treatment recommendations (including surgery). Participants also chose which of six response scales (one visual analogue scale and five Likert scales ranging from four to eight items) was easiest to use, understand, and preferred.A plurality of participants (40.0%) felt their CRS symptoms' current state was best reflected by a 1-month recall period. However, most patients (56.9%) preferred treatment recommendations to be determined by symptoms experienced over a >1 month period. The four- and five-item Likert scales were the easiest to understand (26.0% and 25.4%, respectively) and use (23.4% and 26.7%, respectively). The five-item (26.4% rating it most preferred and 70.9% rating it preferred) and four-item Likert (22.3% rating it most preferred and 56.4% rating it preferred) response scales were most preferred.Future PROMs for CRS should consider assessment of symptoms over a 1-month period and use a four- or five-item Likert response scale to reflect global patient preferences. These findings also inform interpretation of current CRS PROMs.

  View details for DOI 10.1002/alr.23280

  View details for Web of Science ID 001079117100001

  View details for PubMedID 37788156

• Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab. Investigational new drugs Haas, M., Lein, A., Fuereder, T., Schnoell, J., Brkic, F. F., Liu, D. T., Kadletz-Wanke, L., Heiduschka, G., Jank, B. J. 2023; 41 (5): 727-736

  Abstract

  First-line immune checkpoint blockade has improved the prognosis of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but response rates remain low. In this study, we aimed to investigate the prognostic value of CRP and its early kinetics to predict response and survival in R/M HNSCC.A total of 87 patients who received first-line pembrolizumab for R/M HNSCC were analyzed. Three-fold cross-validation was used to estimate cut-off points of CRP at baseline and on-treatment (day 40 ± 10). Treatment response and survival were analyzed according to early CRP kinetics. The neutrophil-to-lymphocyte ratio (NLR) was used as a benchmark for the prognostic performance of CRP.On-treatment CRP below 2 mg/dl, 4x the upper limit of normal (ULN), was associated with increased overall survival (OS), while on-treatment CRP below 3 mg/dl (6x ULN) was correlated with a higher disease control rate (DCR) and increased progression-free survival (PFS). CRP flare-responders and CRP responders showed a higher DCR and longer PFS than CRP non-responders. An NLR above 6 was a negative prognosticator for progression. In multivariable analysis, on-treatment CRP prevailed as the only significant prognosticator for OS (HR: 4.97, CI95%: 2.18-11.32, p < 0.001) and PFS (HR: 2.07, CI95%: 1.07-3.99, p = 0.030).On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely available and cost-effective biomarker.

  View details for DOI 10.1007/s10637-023-01388-x

  View details for PubMedID 37603206

  View details for PubMedCentralID PMC10560194

• Low free triiodothyronine and immune-related hyperthyroidism are associated with overall and progression-free survival in head and neck squamous cell carcinoma treated with pembrolizumab. International immunopharmacology Haas, M., Lein, A., Fuereder, T., Schnoell, J., Brkic, F. F., Campion, N. J., Liu, D. T., Kadletz-Wanke, L., Heiduschka, G., Jank, B. J. 2023; 123: 110799

  Abstract

  Thyroid function is frequently impaired in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In patients treated with pembrolizumab, immune-related adverse events (irAEs) of the thyroid are common. However, the prognostic significance of baseline and on-treatment thyroid dysfunction is currently unclear.This study included 95 patients who received pembrolizumab for R/M HNSCC between 2016 and 2022. Baseline thyroid status, according to serum hormone levels, and irAEs were assessed. Univariable and multivariable Cox regression analyses were performed for overall survival (OS) and progression-free survival (PFS). Furthermore, the best overall response according to the prognostic groups was examined.Low fT3 (HR: 2.52, p = 0.006), immune-related hyperthyroidism (HR: 0.11, p = 0.038), ECOG performance status ≥2 (HR: 3.72, p = 0.002), and platinum-refractory disease (HR: 3.29, p = 0.020) were independently associated with OS. Furthermore, immune-related hyperthyroidism was associated with longer PFS (HR: 0.13, p = 0.007), a higher objective response rate (83% vs. 31%, p = 0.018), and a higher disease control rate (100% vs. 43%, p = 0.008). Thyroid-related autoantibodies were elevated in 40% of thyroid irAEs cases with available measurements. Out of 16 thyroid irAEs, 15 occurred in patients with fT3 above the lower limit of normal.Low fT3 was associated with worse OS. Immune-related hyperthyroidism was correlated with both improved OS and PFS. Baseline fT3 assessment and close on-treatment monitoring of serum thyroid levels may be valuable for risk stratification in R/M HNSCC patients receiving pembrolizumab.

  View details for DOI 10.1016/j.intimp.2023.110799

  View details for PubMedID 37598631

• The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP. Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale Campion, N. J., Brugger, J., Tu, A., Stanek, V., Brkic, F. F., Bartosik, T. J., Liu, D. T., Hoehl, B. S., Gangl, K., Eckl-Dorna, J., Schneider, S. 2023; 52 (1): 56

  Abstract

  Dupilumab significantly improves symptom control in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with large polyps at the initiation of treatment (total polyp score (TPS) ≥ 5) have been the focus in published studies. Patients with significant burden of disease but small polyps (TPS ≤ 4) have not yet been evaluated for clinical response. This study set out to evaluate the benefit of dupilumab treatment on cohorts of small (TPS ≤ 4) compared to large polyps (TPS ≥ 5). Furthermore, benefit of concomitant oral and/or nasal steroid therapy has been evaluated.97 patients with CRSwNP, who were begun on dupilumab between January 2020 and October 2021, were included. All patients were followed-up for 6 months. At each visit they underwent nasal endoscopy, smell identification tests and filled out validated patient questionnaires.Significant drops in TPS were seen in both patient groups after 6 months of therapy, dropping from a median score of 3 to 0 and from 6 to 2 in patients with small and large polyps respectively. Furthermore, a linear mixed model calculated a drop of 22% and 24% in TPS per month in patients with small and large polyps respectively with no significant difference in rate of decline. Finally the model showed that neither oral nor nasal steroids influenced the rate of response to dupilumab therapy.Polyp size at the initiation of dupilumab therapy and whether patients continue to take steroid therapy does not appear to influence effectiveness of dupilumab treatment.

  View details for DOI 10.1186/s40463-023-00663-4

  View details for PubMedID 37674253

  View details for PubMedCentralID PMC10481502

• Experience With the New Active Transcutaneous Bone-Conduction Implant With Smaller Dimensions. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Brkic, F. F., Baumgartner, W. D., Schlott, M., Liu, D. T., Thurner, T., Riss, D., Gstöttner, W., Vyskocil, E. 2023; 169 (3): 615-621

  Abstract

  Recently, the Bonebridge 602 implant was introduced. Its smaller dimensions facilitate implantation even in surgically demanding cases. However, in extreme anatomical conditions, implant lifts are still required. We intended to report on the medical and audiological outcomes of all patients implanted with the implant with a secondary focus on the safety, efficacy, and feasibility of the use of 1-mm lifts.Retrospective cohort study.Tertiary academic center.We retrospectively analyzed all patients implanted with the Bonebridge 602. Patient demographics and surgically-specific data were collected from the medical charts. Furthermore, audiological results were assessed. Outcomes were compared between implantations with versus without lifts.Twenty-one devices were implanted during the study period. Satisfactory audiological results were observed, while no intra- or postoperative adverse events occurred. The majority of patients were daily users at the end of the observation period (n = 20/21, 95.2%), and one patient (n = 1/21, 4.8%) was a nonuser after 6 months of use because of subjective dissatisfaction. Due to anatomical considerations, 1-mm lifts were used in 4 implantations (19.0%). The application of lifts did not result in prolonged surgical times, complications, or shorter time of use, nor did it negatively affect audiometric results.Implantations with the new and smaller Bonebridge were associated with gratifying medical and audiological outcomes. Still, in extreme anatomical conditions, 1-mm lifts are necessary. Nonetheless, surgical placement with the help of lifts seems safe, effective, and feasible, and is a viable option in cases with challenging anatomies due to previous surgeries or anomalies.

  View details for DOI 10.1002/ohn.269

  View details for PubMedID 36939484

• Meteorological extremes and their impact on tinnitus-related emergency room visits: a time-series analysis. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Haas, M., Lucic, M., Pichler, F., Lein, A., Brkic, F. F., Riss, D., Liu, D. T. 2023; 280 (9): 3997-4007

  Abstract

  Extreme weather events are rising due to the accelerating pace of climate change. These events impact human health and increase emergency room visits (EV) for many morbidities. Tinnitus is a common cause of EVs within otolaryngology in Germany and Austria. The effect of extreme weather conditions on tinnitus-related EVs is unknown.A total of 526 tinnitus-related EVs at a tertiary care hospital in Vienna were identified. A distributed lag non-linear model with a maximum lag period of 14 days was fitted to investigate the immediate and delayed effect of single-day and prolonged (three-day) extreme atmospheric pressure, relative humidity, mean temperature, precipitation and mean wind speed on EV rates. Extreme conditions were defined as the 1st, 5th, 95th, and 99th percentile of the meteorological variables. Relative risk (RR) is defined as risk for tinnitus-related EVs at an extreme condition compared to the risk at the median weather condition. Cumulative RR (cRR) is the total cumulated EV risk for a given time period.High relative humidity increased same-day RR for tinnitus-related EVs to 1.75. Both low and high atmospheric pressure raised cRR as early as three days after an event to a maximum of 3.24. Low temperatures mitigated cRR within 4 days, while high temperatures tended to increase risk. Prolonged precipitation reduced cRR within one day.Extreme meteorological conditions are associated with tinnitus-related EV rates. Further investigation into potential causative links and underlying pathophysiological mechanisms is warranted.

  View details for DOI 10.1007/s00405-023-07894-1

  View details for PubMedID 36856808

  View details for PubMedCentralID PMC9976663

• Fluctuations in emergency department visits related to acute otitis media are associated with extreme meteorological conditions. Frontiers in public health Nieratschker, M., Haas, M., Lucic, M., Pichler, F., Brkic, F. F., Parzefall, T., Riss, D., Liu, D. T. 2023; 11: 1153111

  Abstract

  Climate change has been associated with a higher frequency of extreme weather events, resulting in an overall increase in morbidity and mortality. Acute otitis media (AOM) is one of the most common otolaryngological infections and accounts for 1.5% of emergency department visits. This study aimed to identify associations between extreme weather events and the immediate and delayed risks for AOM-related emergency department visits (EV).A total of 1,465 AOM-related EVs were identified in the Vienna General Hospital between 2015 and 2018. A distributed lag non-linear model was applied to evaluate the relationship between extreme weather conditions and the total number of AOM-related EVs per day. The relative risk (RR) and cumulative RR (cRR) of single-day events and extended weather events over three days were analyzed over a lag period of 14 days.AOM-related EVs showed a pronounced seasonality, with the highest occurrence during winter. Single-day weather events affected AOM-related EVs only at high relative humidity. Prolonged extreme weather conditions over three days, however, significantly increased the cRR for AOM-related EVs to 3.15 [1.26-7.88; p = 0.014] and 2.14 [1.14-4.04; p = 0.018] at mean temperatures of -4°C (1st-percentile - p1) and 0°C (p5) on the same day. Relative humidity of 37% (p1) decreased RR to 0.94 [0.88-0.99; p = 0.032] on day 7, while extremely high humidity of 89% (p99) led to an increased cRR of 1.43 [1.03-2.00; p = 0.034] on day 7. Heavy prolonged precipitation of 24mm (p95) reduced cRR beginning day 4 up until day 14 to 0.52 [0.31-0.86; p = 0.012]. Prolonged low atmospheric pressure events of 985hPa (p5) reduced the RR to 0.95 [0.91-1.00; p = 0.03], whereas extremely high atmospheric pressure events of 1013hPa (p99) increased the RR to 1.11 [1.03-1.20; p = 0.008]. Extremely low wind speeds significantly diminished the RR of AOM-related EVs.While single-day extreme weather events had little impact on the occurrence of AOM-related EVs, extended periods of extreme temperatures, relative humidity, precipitation, wind speeds and atmospheric pressure significantly impacted the RR for AOM-related EVs. These findings could help improve healthcare resource allocation in similar climates and aid in educating patients about the role of environmental factors in AOM.

  View details for DOI 10.3389/fpubh.2023.1153111

  View details for PubMedID 37325328

  View details for PubMedCentralID PMC10267338

• Dupilumab reduces symptom burden in allergic rhinitis and suppresses allergen-specific IgE production. Allergy Campion, N. J., Doralt, A., Lupinek, C., Berger, M., Poglitsch, K., Brugger, J., Quint, T., Gangl, K., Sinz, C., Bartosik, T., Liu, D. T., Landegger, L. D., Tu, A., Stanek, V., Berger, U., Bangert, C., Schneider, S., Eckl-Dorna, J. 2023; 78 (6): 1687-1691

  View details for DOI 10.1111/all.15653

  View details for PubMedID 36691369

• The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids. Frontiers in immunology Bartosik, T. J., Campion, N. J., Freisl, K., Liu, D. T., Gangl, K., Stanek, V., Tu, A., Pjevac, P., Hausmann, B., Eckl-Dorna, J., Schneider, S. 2023; 14: 1112345

  Abstract

  Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.

  View details for DOI 10.3389/fimmu.2023.1112345

  View details for PubMedID 37122714

  View details for PubMedCentralID PMC10140405

• Interobserver variability of cochlear duct measurements in pediatric cochlear implant candidates. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery Salkic, A., Yildiz, E., Baumgartner, W. D., Tokic, L., Uscuplic, S., Sarihodzic, S., Brkic, F., Harcinovic, A., Liu, D. T., Brkic, F. F. 2023; 280 (4): 1647-1651

  Abstract

  The objective of the study was to evaluate the proposed cochlear duct length estimation based on the cochlear 'A value'. Furthermore, we assessed the interobserver variability between radiology and otolaryngology attending physicians and otolaryngology trainees.Thirteen pediatric cochlear implant candidates were retrospectively analyzed by three otolaryngology physicians (attending physician, second year, and fourth year trainees) and a radiology attending. The cochlear duct length was calculated based on the formula of Grover et al. The differences in acquired measurements between observers were compared using the Wilcoxon matched signed-rank test.The differences in measurements between the attending otolaryngologist and radiologist were not statistically different, while several significant differences were observed with regard to measurements of attending doctors compared to both residents. In particular, a significant difference between the second year otolaryngology resident and otolaryngology and radiology attending was observed for one side (right ear p = 0.034 and p = 0.012, respectively). Moreover, the fourth year resident calculated significantly different cochlear duct measurements when compared to the attending otolaryngologist (left ear p = 0.014) and radiologist (right ear p = 0.047). Interestingly, differently experienced otolaryngology residents provided significantly different measurements for both ears.Based on these results, cochlear duct length measurement according to the proposed method may be a reliable and cost-effective method. Indeed, otolaryngology training may be sufficient to provide measurements comparable to radiologists. On the other hand, additional efforts should be invested during otolaryngology training in terms of the evaluation of radiological imaging which may increase the capabilities of otolaryngology residents in this regard.

  View details for DOI 10.1007/s00405-022-07639-6

  View details for PubMedID 36074160

  View details for PubMedCentralID PMC9988785

• Olfactory Dysfunction: Etiology, Diagnosis, and Treatment. Deutsches Arzteblatt international Hummel, T., Liu, D. T., Müller, C. A., Stuck, B. A., Welge-Lüssen, A., Hähner, A. 2023; 120 (9): 146-154

  Abstract

  Disorders of the sense of smell have received greater attention because of the frequency with which they occur as a symptom of SARS-CoV-2 infection. Olfactory dysfunction can lead to profound reduction in quality of life and may arise from many different causes.A selective literature review was conducted with consideration of the current version of the guideline issued by the Association of the Scientific Medical Societies in Germany.The cornerstones of diagnosis are the relevant medical history and psychophysical testing of olfactory function using standardized validated tests. Modern treatment strategies are oriented on the cause of the dysfunction. While treatment of the underlying inflammation takes precedence in patients with sinunasal dysosmia, olfactory training is the primary treatment option for other forms of the disorder. The prognosis is determined not only by the cause of the olfactory dysfunction and the patient's age, but also by the olfactory performance as measured at the time of diagnosis.Options for the treatment of olfactory dysfunction are available but limited, depending on the cause. It is therefore important to carry out a detailed diagnostic work-up and keep the patient informed of the expected course and prognosis.

  View details for DOI 10.3238/arztebl.m2022.0411

  View details for PubMedID 36647581

  View details for PubMedCentralID PMC10198165

• Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease. The European respiratory journal Schneider, S., Poglitsch, K., Morgenstern, C., Quint, T., Gangl, K., Sinz, C., Bartosik, T., Campion, N. J., Liu, D. T., Landegger, L. D., Tu, A., Stanek, V., Rocha-Hasler, M., Bangert, C., Eckl-Dorna, J. 2023; 61 (3)

  Abstract

  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.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.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.In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

  View details for DOI 10.1183/13993003.01335-2022

  View details for PubMedID 36549708

  View details for PubMedCentralID PMC10017890

• The Geriatric Nutritional Risk Index (GNRI) as a Prognostic Biomarker for Immune Checkpoint Inhibitor Response in Recurrent and/or Metastatic Head and Neck Cancer NUTRIENTS Haas, M., Lein, A., Fuereder, T., Brkic, F. F., Schnoell, J., Liu, D. T., Kadletz-Wanke, L., Heiduschka, G., Jank, B. J. 2023; 15 (4)

  Abstract

  Malnutrition is a frequent comorbidity in head and neck cancer patients and has been shown to impair immunotherapy response in other cancer types. The geriatric nutritional risk index (GNRI) assesses malnutrition using the patient's ideal weight, actual weight, and serum albumin. The aim of this study was to evaluate the prognostic relevance of malnutrition as determined by the GNRI for the response to immunotherapy in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). A total of 162 patients with R/M HNSCC who received immune checkpoint inhibitors were included. The associations between the GNRI and progression-free survival (PFS), overall survival (OS), and the disease control rate (DCR) were computed. Univariable analysis showed worse PFS for GNRI ≤ 98 (p < 0.001), ECOG performance status (PS) ≥ 2 (p = 0.012), and enteral (p = 0.009) and parenteral (p = 0.015) nutritional supplementation, and worse OS for GNRI < 92 (p < 0.001), ECOG PS ≥ 2 (p < 0.001), and enteral (p = 0.008) and parenteral (p = 0.023) nutritional supplementation. In our multivariable model, GNRI ≤ 98 (p = 0.012) and ECOG PS ≥ 2 (p = 0.025) were independent prognostic factors for PFS. For OS, GNRI < 92 (p < 0.001) and ECOG PS ≥ 2 (p < 0.001) were independent prognostic factors. A GNRI ≤ 98 was significantly associated with a lower DCR compared to a GNRI > 98 (p = 0.001). In conclusion, our findings suggest that the GNRI may be an effective predictor for response to immunotherapy in R/M HNSCC.

  View details for DOI 10.3390/nu15040880

  View details for Web of Science ID 000940099800001

  View details for PubMedID 36839241

  View details for PubMedCentralID PMC9961934

• Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology. The journal of allergy and clinical immunology. In practice Seys, S. F., Hellings, P. W., Alobid, I., Backer, V., Bequignon, E., von Buchwald, C., Cavaliere, C., Coste, A., Deneyer, L., Diamant, Z., Eckl-Dorna, J., Fokkens, W. J., Gane, S., Gevaert, P., Holbaek-Haase, C., Holzmeister, C., Hopkins, C., Hox, V., Huart, C., Jankowski, R., Jorissen, M., Kjeldsen, A., Knipps, L., Lange, B., van der Lans, R., Laulajainen-Hongisto, A., Larsen, K., Liu, D. T., Lund, V., Mariën, G., Masieri, S., Mortuaire, G., Mullol, J., Reitsma, S., Rombaux, P., Schneider, S., Steinsvik, A., Tomazic, P. V., Toppila-Salmi, S. K., Van Gerven, L., Van Zele, T., Virkkula, P., Wagenmann, M., Bachert, C. 2023; 11 (2): 431-438.e2

  Abstract

  Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics.To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology.A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion.A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included.CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE.

  View details for DOI 10.1016/j.jaip.2022.09.043

  View details for PubMedID 36272718

• The psychophysical assessment of gustatory dysfunction in COVID-19 CHEMICAL SENSES Hintschich, C. A., Liu, D. T., Hummel, T. 2023; 48

  View details for DOI 10.1093/chemse/bjad011

  View details for Web of Science ID 001039276300002

  View details for PubMedID 37503717

• Extreme weather conditions influence the frequency of epistaxis-related emergency room visits RHINOLOGY Haas, M., Lucic, M., Pichler, F., Brkic, F. F., Riss, D., Mueller, C. A., Liu, D. T. 2023; 61 (2): 144-152

  Abstract

  Climate change has been associated with an increase in extreme weather conditions. The aim of this study was to identify environmental factors and the effect of extreme weather events (95th percentile) on the risk for epistaxis-related emergency room visits (EV).A total of 2179 epistaxis-related EVs were identified between 2015 and 2018. A distributed lag non-linear model was fitted to investigate the relationship between extreme weather conditions and the total number of epistaxis-related EVs per day. Cumulative relative risk (cRR) is defined as the cumulated daily risk of EV for epistaxis within a stated period after an extreme weather condition compared to the risk of EV at the median value of that weather condition.At a mean daily temperature of 27°C (P95), cRR for epistaxis-related EV was 2.00. At a relative humidity of 39% (P5), cRR was highest on day 3 at 1.59, while extremely high humidity (92%, P99) led to a decreased cRR of 0.7 on day 1. Intense precipitation of 24mm (P99) reduced the cRR on day 3 to 0.38. For prolonged extreme conditions over three days, extremely low wind speed, as well as both high and low atmospheric pressure events, diminished cRR.Extreme temperatures, relative humidity, and precipitation, as well as extended periods of extreme wind speeds and atmospheric pressure, significantly impact cRR for epistaxis-related EVs.

  View details for DOI 10.4193/Rhin22.342

  View details for Web of Science ID 000978883400008

  View details for PubMedID 36351168

• Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD* RHINOLOGY Brkic, F. F., Liu, D. T., Klimbacher, R., Campion, N. J., Bartosik, T. J., Vyskocil, E., Stanek, V., Tu, A., Arnoldner, T., Bangert, C., Gangl, K., Eckl-Dorna, J., Schneider, S. 2023; 61 (4): 320-+

  Abstract

  The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis.All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects.Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner.The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

  View details for DOI 10.4193/Rhin22.408

  View details for Web of Science ID 001047001600001

  View details for PubMedID 37515811

• A homozygous <i>AP3D1</i> missense variant in patients with sensorineural hearing loss as the leading manifestation HUMAN GENETICS Frohne, A., Koenighofer, M., Cetin, H., Nieratschker, M., Liu, D. T., Laccone, F., Neesen, J., Nemec, S. F., Schwarz-Nemec, U., Schoefer, C., Avraham, K. B., Frei, K., Grabmeier-Pfistershammer, K., Kratzer, B., Schmetterer, K., Pickl, W. F., Parzefall, T. 2023; 142 (8): 1077-1089

  Abstract

  Loss-of-function variants in AP3D1 have been linked to Hermansky-Pudlak syndrome (HPS) 10, a severe multisystem disorder characterized by oculocutaneous albinism, immunodeficiency, neurodevelopmental delay, hearing loss (HL), and neurological abnormalities, fatal in early childhood. Here, we report a consanguineous family who presented with presumably isolated autosomal recessive (AR) HL. Whole-exome sequencing was performed on all core family members, and selected patients were screened using array-based copy-number analysis and karyotyping. Candidate variants were validated by Sanger sequencing and assessed in silico. A homozygous, likely pathogenic p.V711I missense variant in AP3D1 segregated with the HL. The family was characterized by thorough medical and laboratory examination. The HL was consistent across patients and accompanied by neurological manifestations in two brothers. The sole female patient was diagnosed with premature ovarian failure. Further findings, including mild neutropenia and reduced NK-cell cytotoxicity in some as well as brain alterations in all homozygous patients, were reminiscent of HPS10, though milder and lacking the characteristic albinism. Previously unrecognized, milder, isolated HL was identified in all heterozygous carriers. A protein model indicates that the variant interferes with protein-protein interactions. These results suggest that a missense variant alters inner-ear-specific functions leading to HL with mild HPS10-like symptoms of variable penetrance. Milder HL in heterozygous carriers may point towards semi-dominant inheritance of this trait. Since all previously reported HPS10 cases were pediatric, it is unknown whether the observed primary ovarian insufficiency recapitulates the subfertility in Ap3d1-deficient mice.

  View details for DOI 10.1007/s00439-022-02506-0

  View details for Web of Science ID 000890115500002

  View details for PubMedID 36445457

  View details for PubMedCentralID PMC10449960

• Eating behavior in patients with smell loss. Frontiers in nutrition Liu, D. T., Prem, B., Sharma, G., Kaiser, J., Besser, G., Mueller, C. A. 2022; 9: 993639

  Abstract

  The objective of this study was to determine how clinical characteristics and validated quality of life (QoL)-measures are associated with eating behavior in patients with olfactory dysfunction (OD).For this cross-sectional study, 150 OD patients of different causes were retrospectively recruited. Olfactory function was measured using the Sniffin' Sticks (TDI), while olfactory-related QoL was evaluated with the Questionnaire of OD negative and positive statements (QOD-NS and QOD-PS). The importance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). The Dutch Eating Behavior Questionnaire (DEBQ) assessed eating behavior based on emotional, external, and restrained eating. Associations were sought between eating behavior metrics (as dependent variables) with clinical characteristics and olfactory-related outcome measures.Emotional, external, and restrained eating behavior deviating from normative standards were reported in 54%, 71.3%, and 68% of patients, respectively. Multivariate regression modeling revealed that emotional eating was associated with age (ß = -0.227, p = 0.032), the body mass index (BMI, ß = 0.253, p = 0.005), the TDI (ß = 0.190, p = 0.046), and the QOD-NS (ß = 0.203, p = 0.049). External eating was associated with OD duration (ß = 0.291, p = 0.005), the TDI (ß = 0.225, p = 0.018), the QOD-PS (ß = -0.282, p = 0.008), and the IOQ (ß = 0.277, p = 0.004). Restrained eating was associated with age (ß = 0.216, p = 0.033), the BMI (ß = 0.257, p = 0.003), male gender (ß = -0.263, p = 0.002), and the IOQ (ß = 0.332, p < 0.001).Clinical characteristics and olfactory outcome measures differentially impact eating styles in OD patients. Our study's results highlight the importance of considering unfavorable changes in eating behavior during clinical counseling.

  View details for DOI 10.3389/fnut.2022.993639

  View details for PubMedID 36438736

  View details for PubMedCentralID PMC9682116

• Pediatric olfactory home testing using regular household items: A cross-over validation study. International journal of pediatric otorhinolaryngology Jaramillo, L., van Egmond-Froehlich, A., Liu, D. T., Prem, B., Renner, B., Mueller, C. A., Besser, G. 2022; 158: 111173

  Abstract

  To develop an olfactory test that can be conducted by an untrained person using common household items and to introduce a German version of the Chemosensory Pleasure Scale for Children (CPS-C(de)).This olfactory home test was developed in phases including evaluation of odors for suitability in a home setting. Parents of 50 children (ages 6-17) were then equipped with instruction manuals and participants were tested twice in a cross-over design. A validated pediatric olfactory test (the Universal Sniff test (U-Sniff)) served as the comparative gold standard. Additionally, a Chinese-English-German "back-and-forth" translation was conducted to establish the CPS-C(de) and was tested for empirical validity.Fourteen items were tested for feasibility, and all were identified on a sufficient rate (≥66%, mean ± SD of 93.3% ± 9.5%). Bland Altman Plot analysis between home testing and the U-Sniff test was nearly identical (bias = 0.04). CPS-C(de) showed similar results to the original Chinese version and a moderate correlation was found between CPS-C(de) scores and Body Mass Index of children (r30 = -0.527, p = 0.003).Remote olfactory testing in children using household items is feasible. The CPS-C(de) may be of value for future olfactory studies.

  View details for DOI 10.1016/j.ijporl.2022.111173

  View details for PubMedID 35561440

• Peripheral eosinophil count and eosinophil-to-lymphocyte ratio are associated with revision sinus surgery EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Bayer, K., Hamidovic, S., Brkic, F. F., Besser, G., Mueller, C. A., Liu, D. T. 2023; 280 (1): 183-190

  Abstract

  The aim of this study was to assess whether hematological indices of the peripheral blood are associated with revision surgery in patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery (ESS).This retrospective, cross-sectional, single-center study included 541 CRS patients that underwent ESS. Demographics and laboratory parameters were retrieved, and group comparisons were performed. We computed binary logistic regression models to associate clinical characteristics (i.e., aeroallergen allergies, asthma, presence of nasal polyps), absolute blood counts of different leukocyte types (i.e., lymphocytes, neutrophils, basophils, and eosinophils), and hematological indices of the peripheral blood [i.e., neutrophil-to-lymphocyte ratio (NLR), basophil-to-lymphocyte ratio (BLR), eosinophil-to-lymphocyte ratio (ELR), and eosinophil-to-neutrophil ratio (ENR)] with revision surgery as outcome.The study population included 435 primary surgeries and 106 revision cases. Patients undergoing revision ESS showed significantly higher absolute preoperative eosinophil counts (381.6 ± 265.6 per µl), ELR (0.205 ± 0.195), and ENR (0.105 ± 0.074) compared to primary cases (all p < 0.001). Binary logistic regression analysis revealed higher odds for revision surgery in patients higher in age (β = 1.026, p < 0.001), with presence of aeroallergen allergies (β = 1.865, p = 0.011), presence of asthma (β = 3.731, p = 0.001), higher preoperative eosinophil counts (β = 1.002, p < 0.001), and higher ELR (β = 155.663, p = 0.015).We found that higher peripheral eosinophil count and higher ELR were associated with revision ESS in CRS patients. Preoperative assessment of hematological indices of the peripheral blood might be a valuable indicator of disease severity, thus facilitating better treatment selection.

  View details for DOI 10.1007/s00405-022-07497-2

  View details for Web of Science ID 000814971200002

  View details for PubMedID 35737101

  View details for PubMedCentralID PMC9813164

• Changes in Acoustic Aspects of Vocal Function in Children After Adenotonsillectomy JOURNAL OF VOICE Brkic, F. F., Liu, D., Campion, N., Leonhard, M., Altumbabic, S., Korlatovic, M., Kaider, A., Kabil-Hamidovic, J., Brkic, F., Vyskocil, E. 2022; 36 (3): 438.e19-438.e24

  Abstract

  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.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.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).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.

  View details for DOI 10.1016/j.jvoice.2020.06.022

  View details for Web of Science ID 000830649200027

  View details for PubMedID 32703724

• Depression Symptoms and Olfactory-related Quality of Life LARYNGOSCOPE Liu, D. T., Prem, B., Sharma, G., Kaiser, J., Besser, G., Mueller, C. A. 2022; 132 (9): 1829-1834

  Abstract

  Patients with olfactory dysfunction (OD) frequently report symptoms of depression. The objective of this study was to determine how clinical characteristics and olfactory-related quality of life (QoL) measures associate with the likelihood for major depressive disorders (MDDs).A total of 192 OD patients were included. Olfactory function was measured using all three subtests of the Sniffn' Sticks test. Olfactory-related quality of life (QoL) was evaluated using the Questionnaires of Olfactory Dysfunction (QOD)-negative (NS) and -positive statement (PS). The likelihood for MDD was assessed using the Patients Health Questionnaire-2 (PHQ-2). Demographics and disease-specific variables (etiology and duration of OD) were collected. Univariate and multivariable analyses were used to associate disease-specific variables and the QOD with the outcome of the PHQ-2. Additionally, the predictive ability of the QOD-NS to predict depressive symptoms was calculated.In univariate analysis, COVID-19 related smell loss, the QOD-NS, and the QOD-PS were significantly associated with the PHQ-2. In multivariable analyses adjusting for QoL measures, the QOD-NS (ß = 0.532, p < 0.001) and sinonasal OD (compared with postinfectious OD) were significantly associated with the PHQ-2 (ß = 0.146, p = 0.047). When omitting QoL measures from multivariable analyses, only COVID-19 related OD (compared with postinfectious OD) was significantly associated with the PHQ-2 (ß = 0.287, p = 0.009). A QOD-NS score > 20.5 had 70.13% sensitivity and 76.32% specificity for detecting symptoms of depression.Our results suggest that COVID-19 related OD might be associated with a higher likelihood for MDD. Furthermore, we showed that the QOD-NS score might be helpful to predict symptoms of depression in OD patients.4 Laryngoscope, 132:1829-1834, 2022.

  View details for DOI 10.1002/lary.30122

  View details for Web of Science ID 000775038500001

  View details for PubMedID 35353380

  View details for PubMedCentralID PMC9544892

• Dedicated Olfaction and Taste Items do not Improve Psychometric Performance of the SNOT-22 LARYNGOSCOPE Liu, D. T., Phillips, K. M., Houssein, F. A., Speth, M. M., Besser, G., Mueller, C. A., Sedaghat, A. R. 2022; 132 (8): 1644-1651

  Abstract

  Previous work has shown the chemosensory dysfunction item of the 22-item Sinonasal Outcome Test (SNOT-22) that assesses problems with "taste/smell" has poor psychometric performance compared with other items on the SNOT-22, which we have hypothesized is due to the simultaneous assessment of two different senses. Our aim was to determine whether distinct smell and taste items in the SNOT-22 would improve psychometric performance.One hundred and eighty-one CRS patients were recruited and completed the SNOT-22. Additional items querying problems with the senses of "smell" and "taste," using the same response scale and recall period were given to study participants. Item response theory (IRT) was used to determine IRT parameters, including item discrimination, difficulty, and information provided by each SNOT-22 item.Confirming previous studies, the chemosensory item of the SNOT-22 (reflecting "taste/smell") had poor psychometric performance. Use of a distinct smell or taste item instead of the combined "taste/smell" item did not improve psychometric performance. However, a dedicated smell question resulted in a left shift of threshold parameters, showing that the dedicated smell item better captures moderate CRS disease burden than the original taste/smell item of the SNOT-22, which by virtue of near-identical IRT parameters appears to more greatly reflect problems with taste.A dedicated smell- or taste-specific item, rather than the combined "taste/smell" item currently in the SNOT-22 does not provide significantly greater psychometric performance. However, a dedicated smell item may better capture moderate CRS disease burden compared with the current chemosensory item on the SNOT-22. Laryngoscope, 132:1644-1651, 2022.

  View details for DOI 10.1002/lary.30120

  View details for Web of Science ID 000775140000001

  View details for PubMedID 35353381

  View details for PubMedCentralID PMC9544569

• Factors Associated with Revision Sinus Surgery in Patients with Chronic Rhinosinusitis JOURNAL OF PERSONALIZED MEDICINE Bayer, K., Hamidovic, S., Besser, G., Mueller, C. A., Liu, D. T. 2022; 12 (2)

  Abstract

  Endoscopic sinus surgery (ESS) is performed in patients diagnosed with Chronic Rhinosinusitis (CRS) refractory to primary medical therapy to achieve adequate disease control. This study aimed to assess which factors and phenotypes of CRS are associated with revision surgery in patients undergoing ESS. This retrospective, single-center study included 667 patients undergoing ESS between 2012 and 2015. We performed group comparisons to detect differences between CRS patients undergoing primary or revision surgery and computed binary logistic regression models. Logistic regression analysis revealed higher odds for revision surgery in CRS patients with older age (p-value < 0.001), male gender (p-value = 0.011), diagnosis of AERD (p-value = 0.005), and presence of asthma (p-value < 0.001) or allergies (p-value = 0.031). Confirming previous studies, we found that the factors of age, CRSwNP, AERD, allergies, and asthma are associated with revision ESS and identified surgical techniques that were predominantly used in revision cases.

  View details for DOI 10.3390/jpm12020167

  View details for Web of Science ID 000763459600001

  View details for PubMedID 35207656

  View details for PubMedCentralID PMC8878652

• Progressive Sensorineural Hearing Loss in Vibrant Soundbridge Users Requiring Cochlear Implantation JOURNAL OF PERSONALIZED MEDICINE Brkic, F. F., Baumgartner, W., Riss, D., Thurner, T., Liu, D. T., Gstoettner, W., Vyskocil, E. 2022; 12 (2)

  Abstract

  Less than 20% of patients with sensorineural hearing loss (HL) provided with the Vibrant Soundbridge (VSB) experience a progressive HL and warrant cochlear implantation (CI). The aim of this study was to identify possible predictors of progressive HL prior to VSB implantation. This retrospective study included all consecutive ears with sensorineural HL provided with the VSB between 1998 and 2016. The patient cohort was divided in a study group comprising patients who underwent CI (CI group) after years of VSB usage and those who did not require VSB replacement during the observational time (control group). Pre- and postoperative pure-tone audiometry thresholds were compared among the two groups. Fifteen out of 81 VSB devices (18.5%) required a CI. The CI group had higher preoperative air-conduction (AC) thresholds than the control group (64.3 ± 8.9 dB vs. 56.3 ± 12.9 dB; p = 0.007) at the time of the VSB implantation. On average, the CI group was significantly younger (39.1 ± 12.3 years vs. 52.6 ± 16.2 years; p = 0.003). In conclusion, VSB users with higher preoperative AC thresholds and younger age at the time of VSB implantation might be at risk for progressive HL within the upcoming eight years and need a further CI surgery. Preoperative counseling is particularly advisable in this patient group.

  View details for DOI 10.3390/jpm12020191

  View details for Web of Science ID 000763112500001

  View details for PubMedID 35207679

  View details for PubMedCentralID PMC8878649

• Chronic rhinosinusitis symptoms differentially impact the likelihood of major depressive disorders LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Liu, D. T., Bartosik, T. J., Campion, N. J., Bayer, K., Tu, A., Victoria, S., Besser, G., Mueller, C. A., Gangl, K., Eckl-Dorna, J., Schneider, S. 2022; 7 (1): 29-35

  Abstract

  The extent to which sinonasal symptoms impact the likelihood of major depressive disorders in chronic rhinosinusitis patients with nasal polyposis (CRSwNP) remains incompletely characterized. In this study, we sought to determine whether individual symptom clusters differentially impact the likelihood of depression in a cohort of CRSwNP patients.We retrospectively included 77 patients with CRSwNP. The severity of sinonasal symptoms was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and grouped according to a previously validated four-subdomain structure: nasal, otologic/facial pain, sleep, and emotional subdomains. The likelihood of major depressive disorders was assessed using the Patient Health Questionnaire-2 (PHQ-2). The clinical characteristic of symptom severity (nasal polyp size) and disease-specific information, such as the number of previous sinonasal surgeries, were also collected.The sleep subdomain was most strongly associated with the likelihood of major depressive disorders, followed by the otologic/facial pain subdomain, after controlling for demographics and clinical indicators of symptom severity (nasal polyp size). We found a SNOT-22 score ≥ 30.5 to be an accurate indicator of scoring higher than or equal to 2 on the PHQ-2 in CRSwNP patients. This had a sensitivity of 83.33% and a specificity of 75.47%.Distinct sinonasal symptom clusters differentially impact the likelihood of depression in CRSwNP patients. Raising awareness for those with severe sinonasal symptomatology might help identify more patients with a higher probability of comorbid depression.Level of Evidence: 4.

  View details for DOI 10.1002/lio2.733

  View details for Web of Science ID 000741934700001

  View details for PubMedID 35155780

  View details for PubMedCentralID PMC8823175

• Seasonal Variations in Public Inquiries into Laryngitis: An Infodemiology Study JOURNAL OF VOICE Liu, D., Besser, G., Leonhard, M., Bartosik, T., Parzefall, T., Brkic, F. F., Mueller, C., Riss, D. 2022; 36 (1): 98-105

  Abstract

  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.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.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).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.

  View details for DOI 10.1016/j.jvoice.2020.04.018

  View details for Web of Science ID 000740945600016

  View details for PubMedID 32439216

• Long-lasting olfactory dysfunction in COVID-19 patients EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Prem, B., Liu, D. T., Besser, G., Sharma, G., Dultinger, L. E., Hofer, S., Matiasczyk, M. M., Renner, B., Mueller, C. A. 2022; 279 (7): 3485-3492

  Abstract

  Olfactory dysfunction (OD) is a common symptom of Coronavirus Disease 2019 (COVID-19). Although many patients have been reported to regain olfactory function within the first month, long-term observation reports vary. Therefore, we aimed to assess the course of chemosensory function in patients diagnosed with COVID-19 within 3-15 months after the infection.One hundred and two patients (71 females and 31 males; mean age 38.8 years) diagnosed with laboratory-confirmed COVID-19 and subjective OD participated in this single-center study 111-457 days after onset of OD. Patients first performed chemosensory tests at home, followed by psychophysical testing (Sniffin' Sticks (TDI), 27-item Candy Smell Test (CST), Taste Strips Test (TST)) in the clinic. Questionnaires regarding importance of olfaction (IOQ) and olfactory-specific quality of life (QOD) were applied at both timepoints.After a mean 216 days (SD 73; range 111-457) between OD onset and follow-up testing, the mean Sniffin' Sticks (TDI) score was 27.1 points (SD 5.8; range 4.25-38.5): 4.0% were anosmic, 72.5% hyposmic, and 23.5% normosmic. At follow-up testing, 73.5% of patients reported improvement, 5.9% deterioration, and 20.6% no change in OD. Moreover, full recovery of self-perceived smell, flavor, and taste was not observed. According to questionnaires, the individual importance of smell did not change, but participants showed improvement in OD-related quality of life (p < 0.001) and had increased parosmia scores (p = 0.014) at follow-up.Our results show that long-lasting OD after SARS-CoV-2 infection is a common symptom. The majority of patients had OD in the range of hyposmia, which was confirmed by comprehensive smell tests.

  View details for DOI 10.1007/s00405-021-07153-1

  View details for Web of Science ID 000716887700001

  View details for PubMedID 34757458

  View details for PubMedCentralID PMC8578909

• Olfactory-related Quality of Life Adjustments in Smell Loss during the Coronavirus-19 Pandemic AMERICAN JOURNAL OF RHINOLOGY & ALLERGY Liu, D. T., Prem, B., Besser, G., Renner, B., Mueller, C. A. 2022; 36 (2): 253-260

  Abstract

  Previous studies provided the first evidence that the importance of olfaction decreases with the duration of olfactory dysfunction (OD).To evaluate differences in olfactory-related quality of life (QoL) between patients with new-onset and persistent smell loss (>4 weeks) during the coronavirus-19 (COVID-19) pandemic and patients with persistent postinfectious OD (PIOD) that were recruited before the pandemic.This was a retrospective study that included 149 patients with self-reported OD. The olfactory-related QoL was measured using the questionnaire of OD (QOD). The QOD measures the degree to which patients (i) adjust and cope with smell loss (QOD-positive statement [QOD-PS]), (ii) suffer from distorted odor perceptions (QOD-parosmia [QOD-PAR]), and (iii) suffer from smell loss in general (QOD-negative statement [QOD-NS]). Self-perceived chemosensory function, demographics, olfactory function, and duration of smell loss were evaluated. Analyses of variance were used to depict differences in QoL-outcomes between different OD groups.All patients included during the COVID-19 pandemic reported an extensive loss of chemosensory functions of smell, taste, and flavor perception. Psychophysical retronasal screening testing showed olfactory impairments in more than half of these patients. One-way analysis of variance and posthoc tests revealed that the QOD-NS was significantly higher in the new-onset OD group than the PIOD group. At the same time, the QOD-PS score was significantly higher in the PIOD and the persistent COVID-19 OD group than in the new-onset OD group.We showed that patients with persistent OD experienced better olfactory-related adjustment and lower QoL-impairment scores than those with recent-onset smell loss, suggesting that the olfactory-related QoL might change as a function of time after symptom onset.

  View details for DOI 10.1177/19458924211053118

  View details for Web of Science ID 000712457600001

  View details for PubMedID 34704454

• Bitter Taste Disrupts Spatial Discrimination of Piperine-Evoked Burning Sensations: A Pilot Study BIOLOGY-BASEL Liu, D. T., Besser, G., Bayer, K., Prem, B., Mueller, C. A., Renner, B. 2021; 10 (9)

  Abstract

  This study aimed to investigate the perceptual similarity between piperine-induced burning sensations and bitter taste using piperine-impregnated taste strips (PTS). This pilot study included 42 healthy participants. PTS of six ascending concentrations (1 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg piperine/dL 96% ethanol) were presented at the anterior tongue, and participants rated perceived intensity and duration. Then, participants performed a spatial discrimination task in which they had to report which of the two strips presented to the anterior tongue contained an irritating stimulus when one strip was always a PTS while the other strip was impregnated with either a single taste quality (sweet or bitter) or a blank strip. Repeated measures one-way ANOVA revealed that burning sensations of higher concentrated PTS were perceived more intense and more prolonged compared to lower concentrated PTS. McNemar's test showed that PTS were identified correctly significantly less often when presented with bitter strips compared to when presented with blank (p = 0.002) or sweet strips (p = 0.017). Our results showed that bitter taste disrupts the spatial discrimination of piperine-evoked burning sensations. PTS might serve as a basis for further studies on disease-specific patterns in chemosensory disorders.

  View details for DOI 10.3390/biology10090886

  View details for Web of Science ID 000699383300001

  View details for PubMedID 34571763

  View details for PubMedCentralID PMC8469466

• Exploring possibilities for shortening the 22-item Sino-Nasal Outcome Test (SNOT-22) using item response theory INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Liu, D. T., Phillips, K. M., Speth, M. M., Besser, G., Mueller, C. A., Sedaghat, A. R. 2022; 12 (2): 191-199

  Abstract

  Even with a high-quality instrument, such as the 22-item Sino-Nasal Outcome Test (SNOT-22), patients can be overwhelmed by repeated completion of questionnaires, leading to nonadherence and reduced data quality. The aim of this study was to evaluate whether the SNOT-22 could be made more concise without losing the valuable information that it provides.A modern psychometric approach, item response theory (IRT), was used on a sample of 800 patients with chronic rhinosinusitis (CRS). The SNOT-22 was refined based on: (1) the item information criteria, retaining only items with above-average information; and (2) the total test information, retaining only the most discriminating items to cover at least 30% of the information within each subdomain. The preliminary validity and reliability of these refined scales were assessed using Cronbach's alpha and Pearson's correlation.Using an IRT approach, we find that it may be possible to shorten the SNOT-22 to an 11-item and six-item version based on psychometric properties. Item information functions of the shortened 11-item and six-item scales demonstrate that both versions accurately covered the CRS symptom-severity continuum. Preliminary reliability and validity analysis showed that both refined scales had good to excellent reliability (Cronbach's alpha ≥ 0.80) and were highly associated with the original full-length scale (r ≥ 0.90).IRT provides data-driven opportunities for the continuous development and refinement of the SNOT-22. While patient and provider input must be accounted for too, our results show that future revisions of the SNOT-22 could include significantly fewer items.

  View details for DOI 10.1002/alr.22878

  View details for Web of Science ID 000689047300001

  View details for PubMedID 34448367

• Response to: HEPA Filters and Airborne Viruses, Bacteria, and Fungi OTOLARYNGOLOGY-HEAD AND NECK SURGERY Liu, D. T., Phillips, K. M., Sedaghat, A. R. 2022; 166 (5): 1005-1006

  View details for DOI 10.1177/01945998211035105

  View details for Web of Science ID 000682566800001

  View details for PubMedID 34311591

• Flavor Enhancement in Daily Life of Patients with Olfactory Dysfunction CHEMOSENSORY PERCEPTION Koenighofer, M., Niebauer, V., Liu, D., Renner, B., Besser, G., Mueller, C. A. 2022; 15 (1): 8-18

  View details for DOI 10.1007/s12078-021-09289-0

  View details for Web of Science ID 000670869900001

• High Prevalence of <i>MYO6</i> Variants in an Austrian Patient Cohort With Autosomal Dominant Hereditary Hearing Loss OTOLOGY & NEUROTOLOGY Frohne, A., Koenighofer, M., Liu, D., Laccone, F., Neesen, J., Gstoettner, W., Schoefer, C., Lucas, T., Frei, K., Parzefall, T. 2021; 42 (6): E648-E657

  Abstract

  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.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.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.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.

  View details for DOI 10.1097/MAO.0000000000003076

  View details for Web of Science ID 000661951100003

  View details for PubMedID 33710140

• Item Response Theory for Psychometric Properties of the SNOT-22 (22-Item Sinonasal Outcome Test) OTOLARYNGOLOGY-HEAD AND NECK SURGERY Liu, D. T., Phillips, K. M., Speth, M. M., Besser, G., Mueller, C. A., Sedaghat, A. R. 2022; 166 (3): 580-588

  Abstract

  The SNOT-22 (22-item Sinonasal Outcome Test) is a high-quality outcome measure that assesses chronic rhinosinusitis-specific quality of life. The aim of this study was to gain greater insight into the information provided by the SNOT-22 by determining its item-based psychometric properties.Retrospective cohort study.Tertiary care academic centers.This study used a previously described data set of the SNOT-22 completed by 800 patients with chronic rhinosinusitis. Item response theory graded response models were used to determine parameters reflecting item discrimination, difficulty, and information provided by each item toward the SNOT-22 subdomain to which it belonged.The unconstrained graded response model fitted the SNOT-22 data best. Item discrimination parameters and total information provided showed the greatest variability within the nasal subdomain, and the item related to sense of smell/taste demonstrated the lowest discrimination and provided the least amount of information overall. The dizziness item provided disparately lower total information and discrimination in the otologic/facial pain subdomain. Items in the sleep and emotional subdomains generally provided high discrimination. While items in the nasal, sleep, and otologic/facial pain subdomains spanned all levels of difficulty, emotional subdomain items covered higher levels of difficulty, indicating greater information provided at higher levels of disease severity.The item-specific psychometric properties of the SNOT-22 support it as a high-quality instrument. Our results suggest the need and possibility for revision of the smell/taste dysfunction item, for example its wording, to improve its ability to discriminate among the different levels of disease burden.

  View details for DOI 10.1177/01945998211018383

  View details for Web of Science ID 000682606000001

  View details for PubMedID 34182821

• Biannual Differences in Interest Peaks for Web Inquiries Into Ear Pain and Ear Drops: Infodemiology Study JOURNAL OF MEDICAL INTERNET RESEARCH Brkic, F. F., Besser, G., Schally, M., Schmid, E. M., Parzefall, T., Riss, D., Liu, D. T. 2021; 23 (6): e28328

  Abstract

  The data retrieved with the online search engine, Google Trends, can summarize internet inquiries into specified search terms. This engine may be used for analyzing inquiry peaks for different medical conditions and symptoms.The aim of this study was to analyze World Wide Web interest peaks for "ear pain," "ear infection," and "ear drops."We used Google Trends to assess the public online interest for search terms "ear pain," "ear infection," and "ear drops" in 5 English and non-English-speaking countries from both hemispheres based on time series data. We performed our analysis for the time frame between January 1, 2004, and December 31, 2019. First, we assessed whether our search terms were most relevant to the topics of ear pain, ear infection, and ear drops. We then tested the reliability of Google Trends time series data using the intraclass correlation coefficient. In a second step, we computed univariate time series plots to depict peaks in web-based interest. In the last step, we used the cosinor analysis to test the statistical significance of seasonal interest peaks.In the first part of the study, it was revealed that "ear infection," "ear pain," and "ear drops" were the most relevant search terms in the noted time frame. Next, the intraclass correlation analysis showed a moderate to excellent reliability for all 5 countries' 3 primary search terms. The subsequent analysis revealed winter interest peaks for "ear infection" and "ear pain". On the other hand, the World Wide Web search for "ear drops" peaked annually during the summer months. All peaks were statistically significant as revealed by the cosinor model (all P values <.001).It can be concluded that individuals affected by otitis media or externa, possibly the majority, look for medical information online. Therefore, there is a need for accurate and easily accessible information on these conditions in the World Wide Web, particularly on differentiating signs and therapy options. Meeting this need may facilitate timely diagnosis, proper therapy, and eventual circumvention of potentially life-threatening complications.

  View details for DOI 10.2196/28328

  View details for Web of Science ID 000667060200010

  View details for PubMedID 34185016

  View details for PubMedCentralID PMC8277359

• Portable HEPA Purifiers to Eliminate Airborne SARS-CoV-2: A Systematic Review OTOLARYNGOLOGY-HEAD AND NECK SURGERY Liu, D. T., Phillips, K. M., Speth, M. M., Besser, G., Mueller, C. A., Sedaghat, A. R. 2022; 166 (4): 615-622

  Abstract

  Current epidemiologic predictions of COVID-19 suggest that SARS-CoV-2 mitigation strategies must be implemented long-term. In-office aerosol-generating procedures pose a risk to staff and patients while necessitating examination room shutdown to allow aerosol decontamination by indwelling ventilation. This review summarizes the current state of knowledge on portable high-efficiency particulate air (HEPA) purifiers' effectiveness in eliminating airborne SARS-CoV-2 from indoor environments.Medline, Embase, Cochrane Databases, and the World Health Organization's COVID-19 Global Literature on Coronavirus Disease.Data sources were systematically searched for original English-language published studies indexed up to January 14, 2021 per the following search strategy: ("HEPA" OR "High-efficiency" OR "High-efficiency particulate air" OR "Efficiency particulate" OR "Purifier" OR "Filter" OR "Cleaner" OR "Filtration") AND ("COVID" OR "COVID-19" OR "SARS-CoV-2" OR "Coronavirus"). Additional relevant studies were identified by searching the reference lists of included articles.Eleven published studies have evaluated the effectiveness of portable HEPA purifiers in eliminating airborne SARS-CoV-2 with relevantly sized surrogate particles. Ten studies evaluated aerosols and submicron particles similar in size to SARS-CoV-2 virions. In all studies, portable HEPA purifiers were able to significantly reduce airborne SARS-CoV-2-surrogate particles. The addition of portable HEPA purifiers augmented other decontamination strategies such as ventilation.Experimental studies provide evidence for portable HEPA purifiers' potential to eliminate airborne SARS-CoV-2 and augment primary decontamination strategies such as ventilation. Based on filtration rates, additional air exchanges provided by portable HEPA purifiers may be calculated and room shutdown times potentially reduced after aerosol-generating procedures.

  View details for DOI 10.1177/01945998211022636

  View details for Web of Science ID 000682538200001

  View details for PubMedID 34098798

• Self-perceived Taste and Flavor Perception: Associations With Quality of Life in Patients With Olfactory Loss OTOLARYNGOLOGY-HEAD AND NECK SURGERY Liu, D. T., Besser, G., Prem, B., Sharma, G., Speth, M. M., Sedaghat, A. R., Mueller, C. A. 2021; 164 (6): 1330-1336

  Abstract

  To evaluate associations between self-perceived chemosensory functions of smell, taste, and flavor perception with olfactory-specific quality of life (QoL) in patients with olfactory dysfunction (OD) and whether these associations would be influenced by other factors, such as duration or etiology of smell loss.Retrospective cohort study.Tertiary care, academic center.Olfactory-specific QoL was measured with the Questionnaire of Olfactory Disorders (QOD). The QOD measures the impact of OD on QoL (QOD-negative statements) and the ability of patients to cope with smell loss (QOD-positive statements). Orthonasal olfactory function, patients' demographics, self-perceived chemosensory perception, and duration and etiology of OD were retrospectively collected in a cohort of patients with quantitative OD. Correlations and multivariable linear regression models were computed to determine possible associations with the outcome measure of QOD-negative and QOD-positive statement scores.A total of 133 patients with OD were included. Analysis revealed a positive correlation between self-perceived taste and flavor perception with QOD-negative statement scores, while self-perceived smell showed no significant correlation. Similarly, longer duration of smell loss and higher age were also correlated with higher QOD-positive statement scores. Multivariable regression models confirmed that self-perceived taste was independently associated with the QOD-negative statement score, while age and duration of OD were independently associated with the QOD-positive statement score.These findings suggest that the impact of diminished flavor perception during eating and drinking has a stronger impact on the QoL of patients with OD as compared with decreased orthonasal olfaction.

  View details for DOI 10.1177/0194599820965242

  View details for Web of Science ID 000656977700030

  View details for PubMedID 33048605

• Retronasal olfactory testing in early diagnosed and suspected COVID-19 patients: a 7-week follow-up study EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Prem, B., Liu, D., Besser, G., Renner, B., Mueller, C. 2022; 279 (1): 257-265

  Abstract

  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.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.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.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.

  View details for DOI 10.1007/s00405-021-06826-1

  View details for Web of Science ID 000650055800001

  View details for PubMedID 33987699

  View details for PubMedCentralID PMC8118104

• PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis CANCERS Parzefall, T., Schnoell, J., Monschein, L., Foki, E., Liu, D., Frohne, A., Grasl, S., Pammer, J., Lucas, T., Kadletz, L., Brunner, M. 2021; 13 (9)

  Abstract

  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.

  View details for DOI 10.3390/cancers13092082

  View details for Web of Science ID 000649950300001

  View details for PubMedID 33923093

  View details for PubMedCentralID PMC8123332

• Annual trends in Google searches provides insights related to rhinosinusitis exacerbations EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Liu, D. T., Schally, M., Schneider, S., Eckl-Dorna, J., Phillips, K. M., Mueller, C. A., Sedaghat, A. R., Besser, G. 2022; 279 (1): 213-223

  Abstract

  Temporal trends of disease-specific internet searches may provide novel insights into seasonal dynamics of disease burden and, by extension, disease pathophysiology. The aim of this study was to define the temporal trends in rhinosinusitis-specific internet searches.This was a cross sectional analysis of search volume for predefined search terms. Google trends was used to explore the volume of searches for five specific search terms related to rhinosinusitis: nose, mucus, sinus, sinusitis, chronic sinusitis, which were entered into Google web search between 2004 and 2019. Results were analyzed within search "context" which included temporally associated related searches. Relative search volume (RSV) was analyzed for English and non-English speaking countries from the Northern and Southern hemispheres. Analysis of seasonality was performed using the cosinor model.The five specific search terms were most related to rhinosinusitis-related search contexts, indicating that they were appropriately reflective of internet queries by patients for rhinosinusitis. The RSV for rhinosinusitis-related terms and more general search terms increased with each passing year indicating constant interest in rhinosinusitis. Cosinor time series analysis revealed inquiry peaks in winter months for all five specific rhinosinusitis-related search terms independent from the hemisphere.Over a 15-year period, Google searches with rhinosinusitis-specific search terms consistently peaked during the winter around the world. These findings indirectly support the model of viral infection or exposure as the predominant cause of acute rhinosinusitis and acute exacerbations of chronic rhinosinusitis.

  View details for DOI 10.1007/s00405-021-06806-5

  View details for Web of Science ID 000641675600004

  View details for PubMedID 33877434

  View details for PubMedCentralID PMC8739168

• Individual importance of olfaction decreases with duration of smell loss RHINOLOGY Liu, D. T., Besser, G., Prem, B., Speth, M. M., Sedaghat, A. R., Mueller, C. A. 2021; 59 (1): 32-39

  Abstract

  The personal importance of a lost neurologic - motor or sensory - function in several conditions has been shown to decrease as the afflicted patient becomes accustomed to not having that function. It is unknown how the importance of olfaction changes with duration of olfactory dysfunction (OD). The aim of this study was to evaluate the association between duration of smell loss and individual significance of olfaction, and whether this relationship would be modulated by other factors, such as etiology of smell loss.This is a retrospective study including a total 163 subjects with different degrees of olfactory function. Individual significance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). Demographics, olfactory function, duration and etiology of OD were evaluated. Group comparisons, bivariate correlations, analyses of variance and multivariate linear regression were applied to detect differences and associations with the outcome measure of IOQ.A significant negative correlation was found between duration of OD and the IOQ. Other important findings include a significantly higher IOQ in patients with posttraumatic- compared to idiopathic OD and in patients with higher aggravation scores compared to the lower aggravation group. Multivariate regression analysis further confirmed that duration of smell loss was independently associated with IOQ.The duration of smell loss is negatively correlated with the individual importance of olfaction, suggesting that patients develop coping mechanisms for adjusting to OD.

  View details for DOI 10.4193/Rhin20.196

  View details for Web of Science ID 000643286800006

  View details for PubMedID 32926009

• Multi-institutional minimal clinically important difference of the 22-item Sinonasal Outcome Test in medically managed chronic rhinosinusitis RHINOLOGY Phillips, K. M., Houssein, F. A., Boeckermann, L. M., Singerman, K. W., Liu, D. T., Sedaghat, A. R. 2021; 59 (6): 552-559

  Abstract

  With a rapid proliferation of clinical trials to study novel medical treatments for CRS, the objective of this study was to study the minimal clinically important difference (MCID) of the 22-item Sinonasal Outcome Test (SNOT-22) in medically-managed CRS patients.A total of 183 medically-treated CRS patients were recruited. All patients completed a SNOT-22 at enrollment and subsequent follow up visit. Distribution and anchor-based methods were used for MCID calculation. These data were combined with data from a previously published study on SNOT-22 MCID in 247 medically managed CRS patients to determine a final recommended MCID value using the combined cohort of 430 patients.In our cohort, distribution- and anchor-based methods -"using both sinus-specific and general health anchors-"provided greatest support for a 12-point SNOT-22 MCID, which had approximately 55% sensitivity but 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. In the combined cohort of 430 patients, we also found greatest support for a 12-point SNOT-22 MCID, which had approximately 57% sensitivity and 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. We also find evidence that the MCID value may be higher in CRS patients without nasal polyps compared to those with nasal polyps.Our results - which include data from patients from two different institutions and regions - confirm a SNOT-22 MCID of 12 in medically managed CRS patients. The SNOT-22 MCID was specific but not sensitive for identifying CRS patients experiencing improvement in symptoms or general health.

  View details for DOI 10.4193/Rhin21.253

  View details for Web of Science ID 000966184300004

  View details for PubMedID 34708838

• Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants RHINOLOGY Liu, D. T., Pellegrino, R., Sabha, M., Altundag, A., Damm, M., Poletti, S. C., Croy, I., Haehner, A., Oleszkiewicz, A., Mandy, C., Hummel, T. 2021; 59 (1)

  Abstract

  Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training.This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult partici- pants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT.A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of age and baseline olfactory function with improvements of overall OF.This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additi- onally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improve- ments after OT.

  View details for DOI 10.4193/Rhin20.262

  View details for Web of Science ID 000643286800013

  View details for PubMedID 32901616

• Decrease and Recovery of Olfactory and Gustatory Function in a Case of SARS-CoV-2 Infection ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY Liu, D., Prem, B., Besser, G., Mueller, C., Renner, B. 2021; 83 (2): 130-133

  Abstract

  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.

  View details for DOI 10.1159/000512875

  View details for Web of Science ID 000595470000001

  View details for PubMedID 33264790

  View details for PubMedCentralID PMC7801983

• The association between COVID-19 cases and deaths and web-based public inquiries INFECTIOUS DISEASES Schnoell, J., Besser, G., Jank, B. J., Bartosik, T. J., Parzefall, T., Riss, D., Mueller, C. A., Liu, D. 2021; 53 (3): 176-183

  Abstract

  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.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.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.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.

  View details for DOI 10.1080/23744235.2020.1856406

  View details for Web of Science ID 000597801900001

  View details for PubMedID 33287607

• Parosmia is Associated with Relevant Olfactory Recovery After Olfactory Training LARYNGOSCOPE Liu, D. T., Sabha, M., Damm, M., Philpott, C., Oleszkiewicz, A., Haehner, A., Hummel, T. 2021; 131 (3): 618-623

  Abstract

  This study aims to determine the association between parosmia and clinically relevant recovery of olfactory function in patients with post-infectious olfactory dysfunction (PIOD) receiving olfactory training.Retrospective cohort study.This was a retrospective cohort study of patients with PIOD that received olfactory training. Adult patients with the major complaint of quantitative smell loss were recruited and treated at several ENT clinics in German between 2008 and 2018. The outcome was based on the association between smell-loss related factors (including parosmia and phantosmia) and clinically relevant changes in overall and subdimension olfactory function of threshold, discrimination, and identification using binary logistic regression analysis.A total of 153 participants with PIOD were included. Clinically relevant improvements in overall olfactory function were more likely in those that had lower baseline olfactory function. Relevant improvements in discrimination function were more likely in those that had lower baseline olfactory function and those that had parosmia at the initial visit. Similarly, relevant improvements in odor identification were more likely in those that had a lower baseline olfactory function and in those who had parosmia at the first visit. Clinically significant improvements in odor threshold were more likely in those who were older in age.This study demonstrated that the presence of parosmia is associated with clinically relevant recovery in olfactory discrimination and identification function in patients with PIOD receiving olfactory training.4 Laryngoscope, 131:618-623, 2021.

  View details for DOI 10.1002/lary.29277

  View details for Web of Science ID 000590266500001

  View details for PubMedID 33210732

• Radiological Markers of the Olfactory Cleft: Relations to Unilateral Orthonasal and Retronasal Olfactory Function DIAGNOSTICS Liu, D. T., Schwarz-Nemec, U., Renner, B., Mueller, C. A., Besser, G. 2020; 10 (11)

  Abstract

  The opacification of the olfactory cleft (OC) has been associated with birhinal orthonasal olfaction in patients with chronic rhinosinusitis (CRS). The aim of this study was to determine the associations between monorhinal and birhinal orthonasal, and retronasal olfaction with radiological markers of the OC in a cohort of patients with CRS. Results were analyzed in a CRS-cohort including 13 patients with nasal polyposis (CRSwNP) and 12 patients with non-eosinophilic CRS (non-eCRS). Monorhinal and birhinal orthonasal olfactory function, and OC-air volume were higher in non-eCRS compared CRSwNP. OC-opacification was also higher in CRSwNP compared to non-eCRS. In the entire CRS-cohort, those with higher OC-opacification showed significantly lower orthonasal and retronasal olfactory test results compared to those with lower OC-opacification across all three coronal planes. Similarly, higher unilateral OC-opacification was also associated with lower ipsilateral orthonasal olfactory function. Correlation analysis further revealed a positive correlation between monorhinal and birhinal orthonasal olfaction with ipsilateral and overall OC-air volume. Likewise, birhinal and monorhinal orthonasal, and retronasal olfactory test results correlated negatively with the overall and ipsilateral Lund-Mackay scores. Monorhinal and birhinal orthonasal, and retronasal olfactory function were lower in CRS patients with higher ipsilateral and overall OC-opacification compared to those with lower OC-opacification.

  View details for DOI 10.3390/diagnostics10110989

  View details for Web of Science ID 000593517000001

  View details for PubMedID 33238552

  View details for PubMedCentralID PMC7700302

• Assessment of odor hedonic perception: the Sniffin' sticks parosmia test (SSParoT) SCIENTIFIC REPORTS Liu, D. T., Welge-Lussen, A., Besser, G., Mueller, C. A., Renner, B. 2020; 10 (1): 18019

  Abstract

  Qualitative olfactory dysfunction is characterized as distorted odor perception and can have a profound effect on quality of life of affected individuals. Parosmia and phantosmia represent the two main subgroups of qualitative impairment and are currently diagnosed based on patient history only. We have developed a test method which measures qualitative olfactory function based on the odors of the Sniffin' Sticks Identification subtest. The newly developed test is called Sniffin' Sticks Parosmia Test (SSParoT). SSParoT uses hedonic estimates of two oppositely valenced odors (pleasant and unpleasant) to assess hedonic range (HR) and hedonic direction (HD), which represent qualitative olfactory perception. HR is defined as the perceivable hedonic distance between two oppositely valenced odors, while HD serves as an indicator for overall hedonic perception of odors. This multicenter study enrolled a total of 162 normosmic subjects in four consecutive experiments. Cluster analysis was used to group odors from the 16-item Sniffin' Sticks Identification test and 24-additional odors into clusters with distinct hedonic properties. Eleven odor pairs were found to be suitable for estimation of HR and HD. Analysis showed agreement between test-retest sessions for all odor pairs. SSparoT might emerge as a valuable tool to assess qualitative olfactory function in health and disease.

  View details for DOI 10.1038/s41598-020-74967-0

  View details for Web of Science ID 000615379800012

  View details for PubMedID 33093474

  View details for PubMedCentralID PMC7581750

• Long-term impact of olfactory dysfunction on daily life WIENER KLINISCHE WOCHENSCHRIFT Auinger, A. B., Besser, G., Liu, D. T., Renner, B., Mueller, C. A. 2021; 133 (19-20): 1004-1011

  Abstract

  Olfactory dysfunction (OD) is common in the general population, affects the quality of life (QoL), and is suspected to cause depression. Long-term outcome data are lacking and there is a need to improve patient counselling regarding prognosis. We aimed to assess subjective long-term recovery rates, the QoL, and mood disturbance in a group of 65 patients, who were affected with OD.Out of 325 patients treated for OD between 2003 and 2009  at a smell and taste clinic, 65 patients were included for a follow-up after an average of 8.6 years. A total of 28 patients answered questionnaires only and 37 patients were provided with an additional smell identification test. Among others, questionnaires included a short form of the World Health Organization quality of life questionnaire (WHOQOL-BREF) and the Beck's depression inventory.In the long run, subjective improvement was stated in 33.8% of all patients, with the highest rate of 42.3% in patients with postinfectious OD. The subjective rating of olfactory function on a visual analogue scale was significantly higher at study follow-up compared to first clinical contact (median 1.25 vs. 4.5; U = 469.5, p = 0.001), as were mean identification scores (6.0 ± 3.0 vs. 8.0 ± 4.0, t(18) = 2.51, p = 0.021). The QoL in general was considered reduced in 40% of all patients at follow-up. Furthermore, participants exhibited only minor, if any, depressive symptoms.Despite negative effects of OD on certain activities in daily life, such as cooking, detecting spoiled food, or personal hygiene, it seems that the patients included in this study adapted to the OD in the long-term. The current findings should aid clinicians in patient counselling.

  View details for DOI 10.1007/s00508-020-01751-5

  View details for Web of Science ID 000581290400001

  View details for PubMedID 33084955

  View details for PubMedCentralID PMC8500863

• Differences in men and women suffering from CRSwNP and AERD in quality of life EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Bartosik, T. J., Liu, D. T., Campion, N. J., Villazala-Merino, S., Janik, S., Dahm, V., Mueller, C. A., Vyskocil, E., Stanek, V., Quint, T., Bangert, C., Eckl-Dorna, J., Schneider, S. 2021; 278 (5): 1419-1427

  Abstract

  While the overall impact of chronic rhinosinusitis (CRS) on patients' health is diverse, many affected individuals have a substantially impaired quality of life (QoL). The aim of this study was to evaluate the impact of sex-associated differences specifically in the subgroups of CRS with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) by assessing QoL parameters in women and men separately.In a retrospective single-center study, 59 patients with CRSwNP (39 males and 20 females) and 46 patients with AERD (18 males and 28 females) were included. Patient-reported outcome measures (PROM) evaluating QoL via the Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) as well as the total polyp score (TPS) were analysed.There was no significant difference in TPS (p = 0.5550) and total SNOT-20 GAV scores (p = 0.0726) between male or female patients with CRSwNP or AERD. Furthermore, no significant sex differences were found within disease groups regarding the subcategories of the SNOT-20 GAV items.Thus, quality of life is severely impaired in patients suffering from various forms of CRS regardless of their sex.

  View details for DOI 10.1007/s00405-020-06418-5

  View details for Web of Science ID 000579660000002

  View details for PubMedID 33063145

  View details for PubMedCentralID PMC8057986

• Peaks in online inquiries into pharyngitis-related symptoms correspond with annual incidence rates EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Brkic, F. F., Besser, G., Janik, S., Gadenstaetter, A. J., Parzefall, T., Riss, D., Liu, D. T. 2021; 278 (5): 1653-1660

  Abstract

  To assess whether web-based public inquiries into pharyngitis-related search terms follow annual incidence peaks of acute pharyngitis in various countries from both hemispheres.Google Trends (GT) was utilized for systematic acquisition of pharyngitis-related search terms (sore throat, cough, fever, cold). Six countries from both hemispheres including four English (United Kingdom, United States, Canada, and Australia) and two non-English speaking countries (Austria and Germany) were selected for further analysis. Time series data on relative search interest for pharyngitis-related search terms, covering a timeframe between 2004 and 2019 were extracted. Following reliability analysis using the intra-class correlation coefficient, the cosinor time series analysis was utilized to determine annual peaks in public-inquiries.The extracted datasets of GT proved to be highly reliable with correlation coefficients ranging from 0.83 to 1.0. Graphical visualization showed annual seasonal peaks for pharyngitis-related search terms in all included countries. The cosinor time series analysis revealed these peaks to be statistically significant during winter months (all p < 0.001).Our study revealed seasonal variations for pharyngitis-related terms which corresponded to winter incidence peaks of acute pharyngitis. These results highlight the need for easily accessible information on diagnosis, therapy, and red-flag symptoms for this common disease. Accurately informed patients might contribute to a reduction of unnecessary clinic visits and potentially cutback the futile antibiotic overuse.

  View details for DOI 10.1007/s00405-020-06362-4

  View details for Web of Science ID 000572287900001

  View details for PubMedID 32968893

  View details for PubMedCentralID PMC7510767

• Ortho- and retronasal olfactory performance in rhinosurgical procedures: a longitudinal comparative study EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Besser, G., Liu, D. T., Sharma, G., Bartosik, T. J., Kaphle, S., Ensslin, M., Renner, B., Mueller, C. A. 2021; 278 (2): 397-403

  Abstract

  Testing olfaction should be an integral part of a clinical work-up in rhinosurgical procedures. Importantly, intact olfactory experience also includes retronasally perceived odors (retronasal olfaction). This study aimed at comprehensively assessing olfaction in patients undergoing rhinosurgical procedures in a comparative manner and evaluating relations to patient-reported outcome measurements (PROMs).Each nostril odor threshold and discrimination, and birhinal identification were tested using Sniffin' Sticks in 14 subjects assigned for septoplasty (SP), 21 for septorhinoplasty (SRP), and 30 for endoscopic sinus surgery (ESS). The 27-Candy-Smell-Test was used to quantify retronasal abilities. Tests were repeated 3 months after surgery.Olfactory dysfunction was preoperatively present in 21% of SP, in 47.6% of SRP, and in 80% of ESS patients. Odor threshold side differences were most frequently found in SRP. Frequently, SRP and ESS patients showed severely impaired retronasal olfaction. Half of included subjects re-visited after 3 months, but olfactory function did not improve overall and rarely on an individual basis to a meaningful extent. Subjective ratings on nasal patency and PROMs were not associated with olfaction nor with changes in olfactory scores.Olfactory function can decisively be impaired a priori not only in patients awaiting sinus surgery, but also in those assigned for functional septorhinoplasty. This impairment may not improve in the short term, which has to be taken into account in patient counseling. This study adds to the current literature on olfaction in rhinosurgery with the extension of retronasal testing.

  View details for DOI 10.1007/s00405-020-06300-4

  View details for Web of Science ID 000560981900004

  View details for PubMedID 32813170

  View details for PubMedCentralID PMC7826311

• Association Between Orthonasal Olfaction and Chemosensory Perception in Patients With Smell Loss LARYNGOSCOPE Liu, D. T., Besser, G., Prem, B., Sharma, G., Koenighofer, M., Renner, B., Mueller, C. A. 2020; 130 (9): 2213-2219

  Abstract

  Self-ratings seem to be the most effortless strategy for assessment of patients' chemical senses. Notably, although flavor perception strongly relies on olfaction, the relationship between self-reported flavor perception and orthonasal olfactory tests have hitherto not been considered. The aim of this study was to investigate the relationship between self-perceived olfactory function (SO), taste (ST), and flavor perception (SF) and smell test results in patients with olfactory dysfunction (OD).We included 203 patients with quantitative OD. Group comparison, bivariate correlation, and ordinal logistic regression were employed to quantify the relationships between predictor variables (age, gender, reason for OD, and orthonasal olfaction-summed scores of threshold, discrimination, and identification [TDI]) and outcomes of SO and SF ("impaired," "average," or "good").Group comparison revealed significant differences between SO and SF (P < .001). Stronger correlations were found between SO and TDI (r = 0.64), compared to SF and TDI (r = 0.27). No relevant correlation was found between ST and TDI (r = 0.10). Higher TDI was associated with odds of higher SO in univariate (odds ratio = 1.25) and multivariable analyses (adjusted odds ratio = 1.23), and both models showed good fit of data. Conversely, regression models on the associations between TDI and changes in SF did not meet the assumption of goodness of fit.We found that higher orthonasal olfactory performance was associated with odds of higher SO in patients with OD, even after controlling for olfactory-relevant factors. To the contrary, similar models based on flavor perception failed to describe these relationships. This indicates for SF and ST to be less represented by the TDI compared to SO.4 Laryngoscope, 130:2213-2219, 2020.

  View details for DOI 10.1002/lary.28773

  View details for Web of Science ID 000537303700001

  View details for PubMedID 32492191

  View details for PubMedCentralID PMC7496293

• Odor Mixtures in Identification Testing Using Sniffin' Sticks: The SSomix Test SCIENTIFIC REPORTS Liu, D., Besser, G., Lang, M., Sharma, G., Pablik, E., Renner, B., Mueller, C. 2020; 10 (1): 8155

  Abstract

  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.

  View details for DOI 10.1038/s41598-020-65028-7

  View details for Web of Science ID 000540520900028

  View details for PubMedID 32424128

  View details for PubMedCentralID PMC7234997

• Eccrine porocarcinoma of the head and neck: Meta-analysis of 120 cases HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Le, N., Janik, S., Liu, D. T., Grasl, S., Faisal, M., Pammer, J., Schickinger-Fischer, B., Hamzavi, J., Seemann, R., Erovic, B. M. 2020; 42 (9): 2644-2659

  Abstract

  The aim of the study is to analyze potential prognostic factors and to evaluate therapy strategies regarding clinical outcome in patients with eccrine porocarcinoma (EPC) of the head and neck.One hundred and sixteen EPC cases from ninety studies and four authors' EPC cases were included in the meta-analysis.At an average follow up of 20.48 months, the 3-year overall survival and regional recurrence rate were 70.3% and 19.0%, respectively. Patients without surgical treatment had a significantly worse 3-year overall survival. Mohs microscopic surgery led to significantly less occurrence of regional recurrences compared to wide excision. An ulcerating lesion, high mitotic activity, and lymphovascular invasion were significant prognostic factors.Surgical resection is the cornerstone in the therapy of EPC and represents the therapeutic modality that offers the best chance of disease-free survival. Due to the high probability of recurrence, close follow-ups are strongly recommended.

  View details for DOI 10.1002/hed.26178

  View details for Web of Science ID 000527030400001

  View details for PubMedID 32314845

• Flavor education and training in olfactory dysfunction: a pilot study EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Besser, G., Oswald, M. M., Liu, D. T., Renner, B., Mueller, C. A. 2020; 277 (7): 1987-1994

  Abstract

  Olfactory training is recommended in olfactory dysfunction (OD) showing promising results. OD patients frequently ask for training modifications in the hope of a better outcome. Also, a lack of knowledge of the flavor system is evident. This investigation sought to implement flavor education (FE) and encourage patients to experience flavors in terms of a flavor training (FT).In included patients (n = 30), OD was either of postinfectious (86.7%) or posttraumatic (13.3%) cause. Chemosensory abilities were tested orthonasally (using Sniffin Sticks = TDI) and retronasally (using the Candy Smell Test = CST). Key points of flavor perception were demonstrated in an educative session. Subjects were instructed to consciously experience flavors out of a list of 50. Effects of FT were explored in two groups (group A and B), with group B starting FT 17 weeks later.FE was appreciated and drop-out rate stayed very low (one participant). Compliance was high and 30.4 ± 12.9 flavors were tried. Overall TDI scores improved in 10 patients (6 group A, 4 group B) in a clinically significant way (> 5.5). For group A (starting FT earlier) rm-ANOVA showed a significant effect of session (timepoint) on CST (p < 0.01).Flavor education is demonstrated as feasible and appreciated in a clinical setting. FT seems to be a welcomed second-line therapy in patients with olfactory dysfunction. This study shows beneficial trends of FT; however, further studies with larger sample sizes and standardized training protocols are needed.

  View details for DOI 10.1007/s00405-020-05950-8

  View details for Web of Science ID 000523399200001

  View details for PubMedID 32248300

  View details for PubMedCentralID PMC7286942

• Self-Administered Testing of Odor Threshold and Discrimination Using Sniffin' Sticks-Reviving the "Odor-Curves-On-Paper" Method CHEMOSENSORY PERCEPTION Besser, G., Liu, D., Renner, B., Mueller, C. A. 2020; 13 (1): 71-77

  View details for DOI 10.1007/s12078-019-09263-x

  View details for Web of Science ID 000524863300007

• 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. Journal of clinical medicine Schneider, S., Campion, N. J., Villazala-Merino, S., Liu, D. T., Bartosik, T., Landegger, L. D., Ahmadi, N., Mueller, C. A., Vyskocil, E., Stanek, V., Quint, T., Bangert, C., Eckl-Dorna, J. 2020; 9 (4)

  Abstract

  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.

  View details for DOI 10.3390/jcm9040925

  View details for PubMedID 32231056

  View details for PubMedCentralID PMC7230739

• Reversible obstruction of the olfactory cleft: impact on olfactory perception and nasal patency INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Besser, G., Liu, D. T., Renner, B., Hummel, T., Mueller, C. A. 2020; 10 (6): 713-718

  Abstract

  Temporary disruption of sensory input can be studied relatively easily for vision or hearing by covering the eyes or ears. In contrast, closing the nostrils affects not only the sense of smell, but also the ability to breathe through the nose and humidify and warm inhaled air. We hypothesized that filling the olfactory cleft (OC) with dissolvable nasal dressing (foam) would temporarily block olfaction while respecting nasal airflow.In 30 healthy volunteers, the OC was unilaterally obstructed in a back-to-front fashion. Orthonasal and retronasal olfactory function were tested before and after foam application. Ratings of odors and subjective nasal patency (SNP) were collected. Peak nasal inspiratory flow (PNIF) was used to measure nasal patency.Foam was safely applied in every case using minimal instruments. No complications were reported. Orthonasal and retronasal test results decreased significantly in overall participants (all p < 0.0008). Indicating temporary anosmia, 3 subjects reached the lowest possible score for odor-threshold testing, with corresponding drops in retronasal test scores. PNIF values before and after foam application were not significantly different (p = 0.11). SNP ratings decreased slightly, but not significantly (p = 0.052). Odor-intensity ratings dropped significantly (all p < 0.05).The OC can be safely obstructed with dissolvable nasal dressing, resulting in a decrease in odor-intensity and orthonasal and retronasal olfactory function test scores. This procedure may serve as a hyposmia model that maintains normal nasal airflow.

  View details for DOI 10.1002/alr.22549

  View details for Web of Science ID 000521600800001

  View details for PubMedID 32216168

  View details for PubMedCentralID PMC7318610

• Winter peaks in web-based public inquiry into epistaxis EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Liu, D., Besser, G., Parzefall, T., Riss, D., Mueller, C. A. 2020; 277 (7): 1977-1985

  Abstract

  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.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.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).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.

  View details for DOI 10.1007/s00405-020-05915-x

  View details for Web of Science ID 000520661500001

  View details for PubMedID 32180015

  View details for PubMedCentralID PMC7286850

• Bitter Taste Perception of the Human Tongue Mediated by Quinine and Caffeine Impregnated Taste Strips ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Liu, D. T., Besser, G., Oeller, F., Mueller, C. A., Renner, B. 2020; 129 (8): 813-820

  Abstract

  Tests for gustatory function have become increasingly important in diagnosis and treatment of patients with taste disorders. While caffeine and quinine hydrochloride solutions have been used for global testing of bitter perception, only quinine has been used to test regional bitter perception by means of taste strips. The aim of the present study was to validate caffeine impregnated taste strips as an alternative to quinine taste strips for assessment of regional bitter perception.A total of 46 healthy volunteers (mean age/range, 23/19-27 years) were included in this study. Quinine and caffeine impregnated taste strips were pairwise presented at different parts of the tongue. Perceived intensity and hedonic dislike were evaluated using labeled magnitude scales. Additionally, gustatory function was assessed using the taste strips test and overall sense of taste was rated using visual analog scales.Assessment of gustatory function demonstrated scores within the normogeusic range in most included subjects (mean/SD, 13.1/2.5). Notably, equally concentrated quinine and caffeine impregnated taste strips placed on different regions of the tongue did not lead to significant differences in perceived intensity or hedonic dislike, whereas quinine and caffeine impregnated taste strips of different concentrations placed on the same region on the tongue led to significant differences of perceived intensity and hedonic dislike. Furthermore, no correlation was found between self-assessment of gustatory function and taste strips scores.Caffeine seems to be a valid bitter compound for regional testing using taste strips and may be used alternatively to quinine.

  View details for DOI 10.1177/0003489420906187

  View details for Web of Science ID 000512258400001

  View details for PubMedID 32028784

  View details for PubMedCentralID PMC7357182

• Body-Mass-Index Associated Differences in Ortho- and Retronasal Olfactory Function and the Individual Significance of Olfaction in Health and Disease. Journal of clinical medicine Besser, G., Erlacher, B., Aydinkoc-Tuzcu, K., Liu, D. T., Pablik, E., Niebauer, V., Koenighofer, M., Renner, B., Mueller, C. A. 2020; 9 (2)

  Abstract

  Odor (including flavor) perception plays a major role in dietary behavior. Orthonasal olfactory function (OOF) has been shown to decrease in obese subjects. Changes in retronasal olfactory function (ROF) after weight loss and in the individual significance of olfaction (ISO) in obesity are yet to be investigated. Firstly, 15 obese subjects were recruited in a pilot study and supported to conventionally lose weight. OOF (Sniffin' Sticks) was measured at the beginning and after 5.6 ± 1.3 months. Eleven subjects re-visited but barely lost weight and no major changes in OOF were observed. Secondly, the body-mass-index (BMI), OOF, and ROF (Candy Smell Test, CST) were recorded in subjectively olfactory-healthy subjects (SOHSs) and additionally the ISO questionnaire was collected in patients with olfactory dysfunction (OD). BMI correlated significantly negatively with odor discrimination (p = 0.00004) in 74 SOHSs and negatively with CST (p < 0.0001) in 66 SOHSs. In 48 SOHSs, there was a gender difference in ISO scores (p = 0.034), but no significant correlation with BMI was found (p > 0.05). ISO scores were significantly higher in 52 OD patients in comparison to SOHSs (p = 0.0382). Not only OOF but also ROF may decline with higher BMI. ISO does not seem to alter with BMI, but olfaction becomes more important once it is consciously impaired.

  View details for DOI 10.3390/jcm9020366

  View details for PubMedID 32013176

  View details for PubMedCentralID PMC7074572

• Retronasal olfactory testing using candies sent by post and for screening purposes: a feasibility study Besser, G., Liu, D., Prem, B., Labloncsik, D., Pablik, E., Mueller, C. A., Renner, B. INT RHINOLOGIC SOC. 2020: 218-225

  Abstract

  The olfactory system is able to detect external odours through the orthonasal- and internal odours through the retronasal route. Flavour perception strongly relies on the sense of smell and this back route. In contrast to orthonasal, retronasal olfactory tests (ROT) are less frequently applied, although testing should be recommended for several reasons. The aim of the present investigation was to propose a suitable form of ROT for home-testing (and postal distribution) and evaluate a retronasal screening test.Initially, 111 participants were tested using a 27-item version of the Candy Smell Test (CST). Fifty-four participants performed retesting, of which 25 subjects did so in a home-setting being supplied with professionally packed "candy-chains". Seven candies were chosen by means of hit rate differences in normosmics and severely hyposmics/anosmics. The 7-CST is designed in a non-forced-choice fashion with same seven flavours to choose from.For the 27-item CST both groups (subjects performing home-testing and those performing retesting at the clinic) showed highly significant test-rest-reliabilities. The 7-CST was capable of discriminating healthy from diseased subjects when being tested in 116 healthy subjects and 47 patients suffering from olfactory dysfunction.The CST is suitable for home-testing and postal distribution. The new 7-item CST can be valuable for rapidly revealing anosmics. These findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.

  View details for DOI 10.4193/Rhin19.230

  View details for Web of Science ID 000562561300006

  View details for PubMedID 32175529

• Surgical management of severe facial trauma after dog bite: A case report ACTA OTO-LARYNGOLOGICA CASE REPORTS Prem, B., Liu, D., Parschalk, B., Erovic, B. M., Mueller, C. A. 2020; 5 (1): 17-22

  View details for DOI 10.1080/23772484.2019.1708746

  View details for Web of Science ID 000532718800001

• Plasma VEGF - a candidate biomarker for response to treatment with bevacizumab in HHT patients RHINOLOGY Liu, D., Frohne, A., Koenighofer, M., Frei, K., Lucas, T., Riss, D., Parzefall, T. 2020; 58 (1): 18-24

  Abstract

  Recurrent epistaxis is the principal symptom of hereditary hemorrhagic telangiectasia (HHT). Currently, there is no standard therapy for this condition. Bevacizumab (anti-VEGF) treatment has been under intense investigation but treatment effects vary greatly between individuals. There are currently no markers to predict anti-VEGF therapeutic response in HHT patients.We evaluated plasma VEGF levels in 13 HHT patients and correlated values with i) degree of epistaxis, measured by visual analog scale (VAS), epistaxis severity score (ESS), and patient bleeding diaries ii) the prevalence of extranasal manifestations, iii) the HHT subtype and iv) the treatment response to intranasal submucosal bevacizumab.Plasma VEGF was elevated in all 13 HHT patients compared to reference levels and showed a moderate correlation with VAS and duration of moderate bleeding events. In patients treated with intranasal submucosal bevacizumab plasma VEGF levels showed a strong correlation with the degree of reduction of mild bleeding events and VAS.The role of plasma VEGF as a potential predictive biomarker for therapeutic response to bevacizumab treatment warrants further investigation in larger prospective studies.

  View details for DOI 10.4193/Rhin19.018

  View details for Web of Science ID 000516765900004

  View details for PubMedID 31681913

• Retronasal olfactory function in patients with smell loss but subjectively normal flavor perception LARYNGOSCOPE Liu, D., Besser, G., Renner, B., Seyferth, S., Hummel, T., Mueller, C. 2020; 130 (7): 1629-1633

  Abstract

  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.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).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).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.4 Laryngoscope, 130:1629-1633, 2020.

  View details for DOI 10.1002/lary.28258

  View details for Web of Science ID 000484539100001

  View details for PubMedID 31471971

  View details for PubMedCentralID PMC7318622

• The Sniffin' Sticks Odor Discrimination Memory Test: A Rapid, Easy-to-Use, Reusable Procedure for Testing Olfactory Memory ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Besser, G., Jobs, L., Liu, D., Mueller, C. A., Renner, B. 2019; 128 (3): 227-232

  Abstract

  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.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).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).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.

  View details for DOI 10.1177/0003489418818189

  View details for Web of Science ID 000457056400008

  View details for PubMedID 30522337

• Olfactory implant: Demand for a future treatment option in patients with olfactory dysfunction LARYNGOSCOPE Besser, G., Liu, D. T., Renner, B., Hummel, T., Mueller, C. A. 2019; 129 (2): 312-316

  Abstract

  Therapeutic options in olfactory dysfunction (OD) are limited. Numerous studies have shown impact of OD on quality of life. Lately, various studies support benefits of olfactory training, but therapy-refractory cases leave doctors and patients locked in a stalemate. An olfactory implant (OI), in analogy to the widely successful cochlear implant, still seems far away from realization. The present study sought to evaluate the demand of OI in patients with OD.Sixty-one patients (28 females and 33 males, mean age/standard deviation 54.9/17.6 years) with OD were recruited. We performed olfactory testing for threshold (T), discrimination (D), and identification (I) using Sniffin' Sticks; summed scores (TDI) allowed us to determine normosmia, hyposmia, and anosmia. We applied questionnaires on the importance of smell (IOS), on olfactory disorders (QOD) and on the interest/willingness for OI, considering the need for skull base/head surgery.Twenty-one patients (34.4%) stated that OI could be a future treatment option for them. This decision significantly correlated with TDI, I, complaint-related questions of the QOD, and IOS (P < .05).With approximately one-third of patients considering OI as a therapy option, this study seems to indicate a demand for OI. In selected patients, with a high degree of complaints, low olfactory test scores, and maybe an additional occupational need for olfactory function, OI might be an option if future developments warrant safety of OI procedures.4 Laryngoscope, 129:312-316, 2019.

  View details for DOI 10.1002/lary.27476

  View details for Web of Science ID 000456677200015

  View details for PubMedID 30145818

  View details for PubMedCentralID PMC6585612

• LANGERHANS CELL SARCOMA: A CASE REPORT AND REVIEW OF THE LITERATURE POLISH JOURNAL OF PATHOLOGY Liu, D. T., Friesenbichler, J., Holzer, L. A., Liegl-Atzwanger, B., Beham-Schmid, C., Leithner, A. 2016; 67 (2): 172-178

  Abstract

  We present the case of a 62-year-old male patient with a three-month history of pain in the left shoulder. Magnetic resonance imaging of the left scapula showed an osteo-destructive lesion. H and E stained sections revealed a Langerhans cell sarcoma, and immunohistochemistry was performed additionally; CD68, CD163, CD14, fascin, HLA-DR, lysozyme, S100 CD1a and langerin showed a positive reaction, while CD20, CD30, CD34, CD31, pan-cytokeratin, AE/1AE3, SMA, desmin, EMA, ERG, INI-1, CD21, CD4, PLAP, MPO and CD117c were negative. We suggested palliative treatment with chemotherapy and radiation. The patient refused any treatment and died 2 weeks later.

  View details for DOI 10.5114/PJP.2016.61454

  View details for Web of Science ID 000383364900012

  View details for PubMedID 27543873