International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 41273228 Real-world evidence in Rhinology 641 641 EN S. Reitsma ENT Department, Amsterdam UMC, Amsterdam, the Netherlands 3387 10.4193/Rhin25.906 When going through the table of contents for this issue of Rhinology, I noticed a few titles containing "real-world" or "real-life", Real-world evidence, real-life evidence, real-world experience, et cetera, all refer to data obtained from day-to-day practice.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40783912 Olfactory outcomes following biological therapy in chronic rhinosinusitis: a systematic review and meta-analysis 642 654 EN D. Patel Luton and Dunstable Hospital, Bedfordshire Hospitals NHS Foundation Trust, Luton, UK J.S. Morris University Hospital of Wales, Cardiff and Vale Health Board, Cardiff, Wales, UK V. Acharya Royal National ENT and Eastman Dental Hospitals, University College London Hospitals NHS Foundation Trust, London, UK P. Andrews Royal National ENT and Eastman Dental Hospitals, University College London Hospitals NHS Foundation Trust, London, UK 3342 10.4193/Rhin24.573 Background: Anosmia is a common, debilitating, and often treatment-resistant symptom of CRS. Biological therapies are a novel and promising treatment for severe and uncontrolled CRS, however, the impact of biological therapy specifically on olfatory dysfunction has not yet been evaluated through systematic review. Methodology: Systematic searches of Ovid MEDLINE, EMBASE and Cochrane Library were performed on 25/05/2024, assessing olfactory outcomes following treatment with biologics. Random-effects meta-analyses were conducted to generate restricted maximum-likelihood estimates for the absolute improvement in each outcome of interest. Results: Systematic searches yielded 801 papers, of which 37 studies comprising of 3284 patients treated with biologics and 1138 controls. In the RCT-only analysis, biologics conferred significat improvements versus control in UPSIT and VAS olfaction (measured as a 0-10 Likert scale). Across all papers, Dupilumab showed significat improvements versus Omalizumab in UPSIT and VAS. Conclusions: Biological therapies are effective in improving olfactory dysfunction secondary to treatment-resistant CRS, with VAS olfaction gains being demonstrated up to 12 months after treatment. Dupilumab shows initial promise over omalizumab; however, cost-effectiveness of biological therapies may limit widespread clinical usage currently.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40927953 Indication for biologics in a real-world cohort of dupilumab treated chronic rhinosinusitis with nasal polyps patients according to international recommendations: evidence from the European CRS Outcome Registry (CHRINOSOR) 655 666 EN G. Mortuaire Otorhinolaryngology-Head and Neck Department, Huriez Hospital, Centre Hospitalier Universitaire (CHU) Lille, Lille, France S.F. Seys Galenus Health, Belgium J. de Kinderen Galenus Health, Belgium G. Bettio Galenus Health, Belgium C. Cavaliere Department of Sense Organs, Sapienza University, Rome, Italy S. Reitsma Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands S. Schneider Department of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria A. Andrianakis Department of General ORL, Head and Neck Surgery, Medical University of Graz, Graz, Austria P-V. Tomazic Department of General ORL, Head and Neck Surgery, Medical University of Graz, Graz, Austria M. Wagenmann Department of Otorhinolaryngology, Universitatsklinikum Dusseldorf (UKD), Dusseldorf, Germany A. Ciofalo Department of Sense Organs, Sapienza University, Rome, Italy Z. Diamant Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium;Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic;University Groningen, University Medical Centre Groningen, Department of Clinical Pharmacology and Pharmacology, Groningen, the Netherlands J. Eckl-Dorna Department of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria W.J. Fokkens Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands M. de Vincentiis Department of Sense Organs, Sapienza University, Rome, Italy C. Holzmeister Department of General ORL, Head and Neck Surgery, Medical University of Graz, Graz, Austria G. Marin Galenus Health, Belgium S. Masieri Department of Oral and Maxillofacial Sciences, Sapienza University, Rome, Italy J.J. Otten Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands K. Scheckenbach Department of Otorhinolaryngology, Universitatsklinikum Dusseldorf (UKD), Dusseldorf, Germany A. Tu Department of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria C. Bachert Clinic for ENT diseases and Head and Neck Surgery, University Clinic Munster, Munster, Germany;Department of Otorhinolaryngology, First Affiliated Hospital, Sun Yat-Sen University, International Airway Research Center, Guangzhou, China CHRINOSOR Consortium* I. Alobid, P. W. Hellings, C. Hopkins, V. Hox, A. Kjeldsen, V. J. Lund, A. Laulajainen-Hongisto, L. Van Gerven CHRINOSOR Consortium 3351 10.4193/Rhin25.157 BACKGROUND: Criteria for biologic treatment of uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) differ across international recommendations and prescription of biologics depends on national reimbursement criteria. CHRINOSOR offers an opportunity to analyse biologic indications in the real-world setting according to international recommendations. METHODS: CRSwNP patients who received dupilumab treatment in the ENT clinic of 6 tertiary centres (5 countries) were included. Baseline demographic and lifestyle factors, NP score, SinoNasal Outcome Test-22 score, visual analogue scale for sinus symptoms, and Asthma Control Test score were retrieved from the medical records. Indication criteria for biologic treatment according to EUFOREA 2021, and EPOS/EUFOREA 2023 recommendations was applied. Dupilumab effectiveness was assessed at baseline, 24 and 52 weeks in relation to these criteria. RESULTS: 61.8% and 79.8% of patients met respectively the EUFOREA 2021 or the EPOS/EUFOREA 2023 indication criteria for biologic treatment. Dupilumab was effective in patients who met or did not meet international criteria for biologic indication. However, patients who met the indication criteria showed overall a more pronounced effect on most of the outcome parameters than patients who did not meet the criteria. CONCLUSIONS: Real-world management of CRSwNP with biologics does not strictly follow the indication criteria established by international recommendations but depends on management criteria established by local authorities. These vary significantly and are either more or less stringent from one country to another. Dupilumab effectiveness in CRSwNP, whether these criteria are met or not, suggests that a broader CRSwNP population may benefit from dupilumab.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40631514 One year mepolizumab outcomes in severe, uncontrolled CRSwNP: a real-life study 667 675 EN E. De Corso Unit of Otorhinolaryngology and Head-Neck Surgery; A. Gemelli "Hospital Foundation IRCCS", Rome, Italy M. Corbi Unit of Otorhinolaryngology and Head-Neck Surgery; A. Gemelli "Hospital Foundation IRCCS", Rome, Italy;Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy G. De Maio Unit of Otorhinolaryngology and Head-Neck Surgery; A. Gemelli "Hospital Foundation IRCCS", Rome, Italy R. Mastrapasqua ENT Department, Rivoli Hospital, ASL TO3, 10098 Rivoli, Italy C. Montuori Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy L.M. D'Auria Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy A. Rizzuti Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy C. Spanu Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy S. Pisciottano Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy G. D’Agostino Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy M.C. Pacilli Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy A. Ortolan Rheumatology and Clinical Immunology, A. Gemelli, Hospital Foundation IRCCS, Rome, Italy A. Rizzi Unit of Allergology e Clinical Immunology, A. Gemelli, Hospital Foundation IRCCS, Rome, Italy J. Galli Unit of Otorhinolaryngology and Head-Neck Surgery; A. Gemelli, Hospital Foundation IRCCS, Rome, Italy;Department of Head-Neck and Sensory Organs; Catholic University of Sacred Heart, Rome, Italy 3321 10.4193/Rhin25.121 BACKGROUND: This study aimed to evaluate the effectiveness of mepolizumab in the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as add-on therapy to intranasal corticosteroids (INCS) in a real-life setting over the first year of treatment. METHODOLOGY: We included 50 patients (28 males; mean age: 56.4 years, range 35-77) who received mepolizumab 100 mg every 4 weeks. The primary objective of this study was to evaluate the reduction in nasal polyp size and improvement in patients' quality of life, measured through symptom-based questionnaires. The secondary objective was to evaluate improvements in smell dysfunction, severity of comorbidities, blood eosinophilia, and the need for surgery or systemic steroids. RESULTS: After 12 months of treatment, the median nasal polyp score (NPS) decreased from 5 to 2 and the mean sino-nasal outcome test-22 (SNOT-22) score decreased from 58.4±21 to 26.1±17.5. Olfaction only slightly improved with a median VAS score decreasing from 10 at baseline to 6 at 12 months. Seven patients remained uncontrolled and required systemic steroids and in 5 cases also endoscopic sinus surgery. CONCLUSIONS: The results support the use of mepolizumab as an effective option in the current standard of care for patients affected by severe, uncontrolled CRSwNP especially in decreasing nasal polyps’ size and improving quality of life, although a minor impact was observed on recovery of smell.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40714983 Effect of calcifediol on chronic rhinosinusitis, a randomized clinical trial 676 684 EN M. Popko-Zagor Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Warsaw, Poland P. Jandziak Seminarium, GP, Bialystok, Poland J. Sierdzinski Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Warsaw, Poland N. Rusetska Department of Experimental Immunology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland E. Sarnowska Department of Experimental Immunology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland 3336 10.4193/Rhin25.070 Background: Recent studies suggest that intranasally administered vitamin D can be an effective treatment for patients with chronic rhinosinusitis (CRS). We performed a double-blind, placebo-controlled, randomized clinical trial to evaluate the effect of adding calcifediol to saline sinus irrigation with budesonide for patients with CRS. Methods: A total of 113 adult patients with CRS were enrolled. Patients were randomized to either calcifediol (n = 58, 51%) or placebo (n = 55, 49%) lavage and were instructed to irrigate both nasal cavities twice daily for 21 days, with either calcifediol or placebo dissolved in a solution of saline with budesonide. The primary outcome measure was the change in Sino-Nasal Outcome Test (SNOT-22) scores, endoscopic examination scored by the Lund-Kennedy (L-K) grading system, and physician-reported response to treatment, as measured with decreased need for nasal steroids/cessation of nasal steroids in the calcifediol group compared with the placebo group. The secondary outcome measures included the change in serum 25(OH)D concentration and the correlation of results with other clinical data. Results: 108 patients completed the trial. Significant changes in SNOT-22 score, L-K score and serum 25(OH)D were reported between the 2 study groups. A significant percentage of participants in the calcifediol group could cease nasal steroids. Conclusion: Calcifediol in saline nasal lavage with budesonide results in clinically significant benefits beyond the benefits of saline with budesonide alone for patients with CRS.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40970361 Corticosteroid responsive olfactory dysfunction in chronic rhinosinusitis: what does it mean? 685 695 EN K.A. Archer Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA J.C. Mace Department of Otolaryngology-Head and Neck Surgery, Oregon Health Sciences University, Portland, OR, USA T.L. Smith Department of Otolaryngology-Head and Neck Surgery, Oregon Health Sciences University, Portland, OR, USA Z.M. Soler Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA R.J. Schlosser Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA J.A. Alt Department of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, UT, USA J. Mattos Department of Otolaryngology-Head and Neck Surgery, University of Virginia, Charlottesville, VI, USA V.R. Ramakrishnan Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA 3356 10.4193/Rhin24.207 BACKGROUND: In the setting of chronic rhinosinusitis (CRS), olfactory improvement with corticosteroids suggests reversibility and preserved function. While self-rated olfactory function does not replace psychophysical measures of olfactory function, our goal is to investigate if self-reported pre-operative corticosteroid-responsive olfactory dysfunction (CROD) is a predictor of post-operative olfactory improvement in patients with CRS undergoing sinus surgery. METHODOLOGY: We performed a prospective, observational study of patients with refractory CRS with and without nasal polyposis and pre-operative olfactory dysfunction undergoing sinus surgery. Patients were characterized into corticosteroid-responsive and non-corticosteroid-responsive based on a survey response. Patient outcome measures for Sniffin Sticks, Olfactory Cleft Endoscopy Score (OCES), Questionnaire of Olfactory Disorders (QOD-NS), and Sino-nasal Outcomes Test (SNOT-22) were recorded pre- and post-operatively. RESULTS: A total of 253 participants were included. Patients with CROD were more likely to have comorbid nasal polyposis, asthma, and aspirin sensitivity. Patients with CROD had significantly better post-operative improvement in OCES total scores and QOD-NS total scores compared to patients without CROD. CONCLUSIONS: In conclusion, patients with CRS and CROD are more likely to have a greater improvement in olfactory dysfunction post-operatively by several measures of olfactory outcomes. This suggests that corticosteroid responsiveness is a clinical predictor of preserved function and reversibility and can be used as a simple clinical prognostic factor.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40923196 Modification of the Sniffin Kids Test for olfactory testing in a population of Polish children 696 705 EN K. Dżaman Department of Otolaryngology, Centre of Postgraduate Medical Education, Warsaw, Poland R. Jowik Department of Otolaryngology, Centre of Postgraduate Medical Education, Warsaw, Poland W. Miechowski Department of Otolaryngology, Centre of Postgraduate Medical Education, Warsaw, Poland K. Piskadlo-Zborowska Department of Otolaryngology, Centre of Postgraduate Medical Education, Warsaw, Poland M. Szarras-Czapnik Department of Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland D. Raczkiewicz Department of Medical Statistics, School of Public Health, Centre of Postgraduate Medical Education, Warsaw, Poland K. Czerwaty Department of Otolaryngology, Centre of Postgraduate Medical Education, Warsaw, Poland 3348 10.4193/Rhin23.271 BACKGROUND: Smell tests in children need to be standardized and validated, include odors familiar to children, and be defined by age-dependent standards. This study aimed to adapt the Sniffin Kids Test (SKT) for Polish children and conduct validation and evaluation of the Sniffin Kids Poland Test (). METHODOLOGY: The study included 382 children (4-14 years old) recruited in Poland, who were allocated into healthy (n=343) and sick (with subjective olfactory disorders, n=39), divided into 3 age subgroups, but also 13 anosmic children with Kallmann syndrome (KS) and olfactory bulb aplasia. Firstly, the smell testing was performed in 382 children using SKT, and subsequently, SKPOL was created using odors identified by at least 75% of healthy individuals. The 10th percentile of SKPOL results in healthy children was adopted as a cutoff point between norm and pathology. SKPOL validation and reliability were assessed using the KS group results. RESULTS: Odor identification score in SKT of Polish children in healthy 6-14-year-olds did not meet the criteria for a test adapted for population studies. An odor identification rate was obtained for 5 odors in 4-7 years old, 7 odors in 8-10 years old, and 9 odors in 11-14 years old. SKPOL was created using these odors. Age-dependent norms for SKPOL were 26.5+-7.5 to 29.1+-7.4, respectively. All KS children had SKPOL results below the 10th percentile. CONCLUSIONS: Validation and evaluation of SKPOL confirmed good adaptation and high reproducibility of the test for Polish children aged 4-14 years.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 41058606 Web-application guided bimodal olfactory training for COVID-19 patients: a randomized trial 706 715 EN C. Vandersteen Institut Universitaire de la Face et du Cou, Centre Hospitalier Universitaire, UR2CA-REBOOT, Universite Cote d'Azur, Nice, Alpes- Maritimes, France;Universit Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France M. Payne Universite Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France;Universite Cote d'Azur, Departement d'Orthophonie de Nice, UFR Medecine, Nice, Alpes-Maritimes, France C. Becker Givaudan Perfumery school Director, Argenteuil, France S. Bernier Institut NeuroMod, INRIA Centre de recherche Sophia Antipolis, Universite Cote d'Azur, Sophia Antipolis, Alpes-Maritimes, France A. Derreumaux Universite Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France N. Guevara Institut Universitaire de la Face et du Cou, Centre Hospitalier Universitaire, UR2CA-REBOOT, Universite Cote d'Azur, Nice, Alpes- Maritimes, France L. Castillo Institut Universitaire de la Face et du Cou, Centre Hospitalier Universitaire, UR2CA-REBOOT, Universite Cote d'Azur, Nice, Alpes- Maritimes, France A. Plonka Universite Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France;Institut NeuroMod, INRIA Centre de recherche Sophia Antipolis, Universite Cote d'Azur, Sophia Antipolis, Alpes-Maritimes, France V. Manera Universite Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France;Universite Cote d'Azur, Departement d'Orthophonie de Nice, UFR Medecine, Nice, Alpes-Maritimes, France;Institut NeuroMod, INRIA Centre de recherche Sophia Antipolis, Universite Cote d'Azur, Sophia Antipolis, Alpes-Maritimes, France X. Fernandez Institut de Chimie de Nice, Universite Cote d'Azur, Nice, Alpes-Maritimes, France A. Gros Institut Universitaire de la Face et du Cou, Centre Hospitalier Universitaire, UR2CA-REBOOT, Universite Cote d'Azur, Nice, Alpes- Maritimes, France; Universite Cote d'Azur, laboratoire CoBTeK, Nice, Alpes-Maritimes, France;Universite Cote d'Azur, Departement d'Orthophonie de Nice, UFR Medecine, Nice, Alpes-Maritimes, France 3363 10.4193/Rhin24.273 BACKGROUND: Many Post-Acute COVID-19 Syndrome (PACS) patients continue to experience persistent dysosmia up to two years post-pandemic. Cognitive and semantic memory functions, along with olfactory associative areas, may be affected in PACS without olfactory recovery. Visual-olfactory bimodal olfactory training may stimulate these areas. This study evaluates the olfactory recovery using a new bi-modal training kit, MaMadeleine assisted by a web application. METHODOLOGY: A prospective randomised study (Nov 2021-June 2022) included PACS patients aged >=14 with post-infectious olfactory dysfunction. Patients were randomized for two months of simple (A) or semantic (B) visual-olfactory training. Evaluations included clinical assessments, Sniffin' Sticks Tests, and quality-of-life questionnaires. Adherence to treatment was monitored via the web application. RESULTS: We included 83 patients, on average 13+-5.6 months after COVID-19. Olfactory training using MaMadeleine led to subjective orthoand retro-nasal olfactory improvement in 79.4% (n=58) and 58.9% (n=43) of patients, respectively, with Sniffin' Sticks Test scores increasing from 26.5+-7.5 to 29.1+-7.4. Both groups saw a 20% decrease in parosmia and phantosmia. No significant differences in recovery were observed between groups, although exploratory findings in a small subgroup (n=10) with semantic memory impairment suggest a possible benefit of bimodal training, warranting further investigation. Quality of life improved significantly in both groups. Adherence was better in group B than in group A. CONCLUSIONS: MaMadeleine training improves subjective olfactory function, psychophysical test results, and quality of life in PACS patients with olfactory dysfunction. Multimodal training enhances adherence. Further studies are needed in semantic memory-impaired patients.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40824150 Natural history of incidental paranasal sinus fungal balls: evidence from a decade-long imaging-based cohort 716 724 EN I. Margulis Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel;Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel Y. Shopen Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel;Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel T. Zaseeva Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel;Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel S. Eid Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel;Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel I. Yakubovich Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel T. Shochat Statistical Consultant, Rabin Medical Center, Petah Tikva, Israel E. Soudry Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel;Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel 3343 10.4193/Rhin25.117 INTRODUCTION: There is no data in the literature regarding the appropriate management of patients with an incidental finding of paranasal sinus fungal ball (FB) or its natural history. This study examined the long-term outcomes of a cohort of patients with FB, pooled from a large imaging database.METHODS: A retrospective screening of 108,369 head imaging studies for phrases indicative of FB in a tertiary referral center, during 2012-2023. RESULTS: A total of 1,716 patients were identified according to the search criteria and their imaging studies were evaluated by the authors. 83 (4.83%) patients were noted to have findings compatible with FB. Mean age was 78.3+-11.8 years and median follow-up (FU) time was 59.2 (10.2-178.8) months. The most involved sinuses were maxillary (50.6%) and sphenoid (43.4%). Intra-sinus calcifications and sinus opacification were observed in all patients. Additionally, sinus wall bony sclerosis, and erosion were observed in 44.5% and 2.4%, respectively. 5 (6.0%) patients underwent surgery during follow-up. 4 (4.8%) patients had FB-associated symptoms, and 1 patient (1.2%) had posterior sphenoid sinus wall erosion. No morbidity or complications were reported for the remaining 78 (94%) patients who did not receive treatment. During a median interval of 50 months, 34/49 (69.4%) patients with >=2 consecutive imaging studies showed no worsening of radiographic findings. CONCLUSION: During an average FU of 5 years of patients with incidental FB findings, the vast majority remained asymptomatic and without complications. Thus, upfront surgical intervention for asymptomatic FB in elderly fragile patients may not be mandatory and a clinical and imaging FU can be a reasonable treatment plan.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40853360 Endoscopic endonasal versus transcranial approaches for trigeminal schwannomas: choosing the optimal surgical corridor based on tumour traits 725 735 EN L-S. Pan Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China S-Z. Xing Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China S-F. Li Department of Otorhinolaryngology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China Z-C. Ye Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China J. Wu Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China;Jiangxi Key Laboratory of Neurological Diseases, Nanchang, China S-H. Xie Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China;Jiangxi Key Laboratory of Neurological Diseases, Nanchang, China C-M. Xu Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China F. Ouyang Department of Radiology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China Y-C. Wang Department of Ophthalmology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China J-Y. Zhang Academic Affairs Office, Nanchang University, Nanchang, China H. Ding Department of Neurosurgery, Jiangxi Provincial People’s Hospital, Nanchang, China L-M. Xiao Department of Neurosurgery, Jiangxi Cancer Hospital, Nanchang, China B. Tang Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China;Jiangxi Key Laboratory of Neurological Diseases, Nanchang, China T. Hong Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China;Jiangxi Key Laboratory of Neurological Diseases, Nanchang, China X. Wu Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China;Jiangxi Key Laboratory of Neurological Diseases, Nanchang, China 3345 10.4193/Rhin25.245 BACKGROUND: Two primary surgical approaches, the transcranial approach (TCA) and the endoscopic endonasal approach (EEA), offer distinct advantages and disadvantages, but studies have yet to compare their outcomes for trigeminal schwannoma (TS) resection systematically. METHODOLOGY: A retrospective review of TSs between 2013 and 2023 was performed, with clinical characteristics, surgical outcomes, and follow-up data collected and analyzed. The patients were divided into two surgical groups, and tumours within each group were further classified according to the Samii system into middle fossa (type A), dumbbell-shaped involving middle and posterior fossae (type C), and extracranial with intracranial extension (type D), excluding posterior fossa (type B). RESULTS: A total of 101 patients (44 via EEA, 57 via TCA) were included. The two groups exhibited comparable baseline characteristics, except for the prevalence of dizziness in the pooled data (types A, C, and D). In pooled data and type A tumours, the EEA was associated with a statistically significant differences in higher gross total resection rate, shorter operative time, lower intracranial infection rate, and greater improvement in facial numbness. EEA was also significantly associated with a lower neurological deficits and higher Karnofsky Performance Scale scores in pooled data. Both approaches resulted in similar outcomes for type C tumours. EEA was advantageous for type D tumours in the infratemporal fossa, pterygopalatine fossa, and medial orbital regions, and no neurological deficits were observed. CONCLUSIONS: The optimal outcome of the surgical approach and minimization of morbidity for these complicated lesions depend on the meticulous selection of cases.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40923216 Serpentine Sign: evidence of airway compensation in patients with empty nose syndrome 736 743 EN P-W. Wu School of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan F.T-N. Yu School of Medicine, Chang Gung University, Taoyuan, Taiwan T-J. Lee School of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Department of Otolaryngology, Xiamen Chang Gung Hospital, Xiamen, China C-C. Huang School of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, Taiwan P-H. Chang Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, Taiwan C-C. Huang School of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3349 10.4193/Rhin25.230 BACKGROUND: This study aimed to evaluate the presence of Serpentine Signs on computed tomography (CT) images and its impact on the clinical symptoms in patients with empty nose syndrome (ENS). METHODS: A retrospective study analysed patients with ENS enrolled in previous studies. The clinical characteristics and results of ENS-specific questionnaire evaluations were reviewed. The ratio of the maximal to minimal thickness (M/m ratio) of the septal mucosa was also calculated to demonstrate the degree of swelling. Mucosal swelling was defined as a thickness greater than twice that of the surrounding mucosa. A Serpentine Sign was identified by the presence of two or more mucosal swellings on one side of the central nasal septum. RESULTS: Seventy-one (74.0%) of the 96 enrolled patients with ENS exhibited Serpentine Signs on CT images. Patients with the Serpentine Sign had significantly lower symptom scores on the ENS 6-item Questionnaire (ENS6Q) and 25-Item Sino-Nasal Outcome Test (SNOT-25). Regression analysis revealed that the ENS6Q, SNOT-25, sleep, psychological, and empty nose symptom domains were significantly associated with the Serpentine Sign. The M/m ratio of the nasal septal mucosa significantly decreased in 39 participants with available postoperative CT images 6 months after nasal reconstruction surgery, along with an improvement in ENS6Q and SNOT-25 scores. CONCLUSION: The Serpentine Sign was associated with fewer ENS symptoms in patients with ENS. The severity of septal mucosal swelling decreased after surgical reconstruction. These results imply a significant impact of airflow alteration due to over-reduction of the inferior turbinate on the nasal mucosa.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 41143434 Ex-vivo and replica measurements of nasal tract resonances 744 752 EN M. Havel Department of Otorhinolaryngology, Section Phoniatrics, University of Munich LMU, Munich, Germany J. Sundberg Department of Speech Music and Hearing KTH, Stockholm, Sweden 3375 10.4193/Rhin24.382 BACKGROUND: The nose is a resonator, the acoustic properties of which are determined by its shape. Due to its complex anatomy and hence intricate acoustical response the identification of universal acoustic characteristics of nasalized vowels and consonants is challenging. The purpose of this investigation was to 1) elucidate acoustic properties of the nasal resonator, 2) document how the paranasal sinuses affect it, and 3) examine if 3D-replicas of anatomical specimens provide reliable data for acoustic analysis. METHODS: In this experimental study the resonance properties of the nasal tract were analyzed in ex-vivo specimens as well as in their 3-D replicas. Their sound transfer characteristics were recorded by sending a sinewave, gliding from low to high frequency from an earphone airtightly sealed into the velopharyngeal port. The response was picked up at a nostril. The acoustical influence of the sinuses was reversibly eliminated by occlusion of the sinus ostia. RESULTS: Response curves of the nasal tract were found to possess two main resonances, one in the vicinity of 600-750 Hz and one in the 2500 â€" 3500 Hz range. Comparison of the acoustical responses obtained while including and excluding the influence of the paranasal cavities showed a great inter-individual variation in the response curve morphology. The cavities were found to introduce V-shaped sound level minima in the response curves. CONCLUSIONS: When the influence of the paranasal cavities is eliminated, the nasal cavity presents two main resonances, which are determined mainly by its anatomical length. The resonances of the paranasal cavities introduce minima and maxima in the frequency response of the nasal tract at frequencies with substantial inter-individual variation. Replicas of anatomical specimens provide reliable data for acoustic analysis.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40781873 Identification of host-microbiome interactions in nasal diseases using multiomics integration 753 764 EN Y. Liang Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China Z. Chen LC-BIO Technologies CO., LTD., Hangzhou, China C. Zhang Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China; Department of Head and Neck Tumor Surgery, Shanxi Provincial People's Hospital, Shanxi, China Z. Li Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China J. Liu Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China W. Sun LC-BIO Technologies CO., LTD., Hangzhou, China J. Li LC-BIO Technologies CO., LTD., Hangzhou, China J. Zhi Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China G. Zhang Department of Otorhinolaryngology Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Tianjin, China 3341 10.4193/Rhin24.386 Background: Nasal dysbiosis is implicated in the pathogenesis of nasal diseases, yet microbiome-host interplay remains poorly understood. Methodology: We conducted a cross-sectional analysis comparing 43 CRSwNP patients, 27 NIP patients, and 34 controls using dual 5R 16S rRNA sequencing and host transcriptomics to characterize microbiome profiles and host-microbial interactions. Results: Distinct microbiome patterns were identified in CRSwNP and NIP mucosal microenvironments. Host-microbiome interaction analysis revealed both shared and disease-specific associations. Common to both disorders were immune-related pathway enrichments, while CRSwNP uniquely demonstrated microbial recognition/immune activation links and NIP showed predominant proliferative pathway correlations. Notably, Bayesian network analysis identified Geobacillus stearothermophilus abundance as significantly associated with NF-kB pathway activation in nasal polyps - a finding subsequently experimentally validated. Conclusion: Our findings delineate disease-specific microbiome-host interplay in nasal pathologies, with CRSwNP exhibiting immune-focused interactions versus NIP's proliferative associations. These insights advance our understanding of nasal disease mechanisms and support the development of targeted microbiome-modulating therapies.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40657826 De-escalation of dupilumab for chronic rhinosinusitis with nasal polyps: analysis of outcomes after modified dosing regimen 765 767 EN L. D’Ascanio Department of Otolaryngology, AORMN, Fano-Pesaro, Italy P. Gradoni Department of Otolaryngology, AORMN, Fano-Pesaro, Italy L. Pierucci Department of Otolaryngology, University of Perugia, Perugia, Italy G. Motta Department of Otolaryngology, University of Campania "Luigi Vanvitelli", Italy N.Y. BuSaba Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School and Massachusetts Eye and Ear Institute, Boston, MA, USA M.J. Brenner Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, MI, USA A. Di Stadio Department of Otolaryngology, University of Campania, University of Campania "Luigi Vanvitelli", Naples, Italy 3326 10.4193/Rhin25.151 Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition with severe impacts on quality of life and substantial economic costs. Dupilumab targeting the underlying T2 inflammation in CRSwNP showed promising results; however, it is unknown if intensive regimens must be maintained in responders to prevent relapse. In 2019, FDA and the European Commission approved Dupilumab 300 mg administered subcutaneously every two weeks for CRSwNP. We hypothesized that disease control might be maintained by reducing the frequency of administration in patients who initially well answered to the standard treatment. To date the benefit of de-escalation was only analyzed in short time. We wanted to understand if a de-escalation regimen could be introduced without compromising disease control in long follow-up; to this aim we de-escalated Dupilumab at 300 mg every four weeks following a year of conventional bi-weekly administration.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 41143389 Clinical management of dupilumab-induced blood eosinophilia in CRSwNP: a practical algorithm 768 770 EN E. De Corso Otolaryngology, Head and Neck Surgery, Rhinology, A. Gemelli Universitary Hospital Foundation, IRCSS, Rome, Italy M. Caminati Allergy Unit and Asthma Center, Verona Integrated University Hospital and Department of Medicine, University of Verona, Italy P.W. Hellings Department of Otorhinolaryngology, Head and Neck Surgery, UZ Leuven, Leuven, Belgium C. Montuori Department of Head-Neck and Sensory Organs, Catholic University of Sacred Heart, Rome, Italy S. Reitsma Department of Otorhinolaryngology and Head/Neck surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands V. Backer Department of Otorhinolaryngology, Head and Neck surgery, and Audiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark W.J. Fokkens Department of Otorhinolaryngology and Head/Neck surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 3374 10.4193/Rhin25.266 Dupilumab is widely recognised as a highly effective therapy for severe chronic rhinosinusitis with nasal polyps (CRSwNP). A rise in blood eosinophil count (BEC) might occur during treatment across all approved indications. In CRSwNP, dupilumab-induced blood eosinophilia (DIBE) is typically of early onset, transient, and asymptomatic without impairing the drug’s efficacy. A review including data from 11 clinical trials on all approved dupilumab indications reported eosinophilia-related clinical manifestations in only 7 of 4,666 patients receiving dupilumab. Real-world studies confirm DIBE is largely benign, with only rare AEs requiring dupilumab discontinuation such as eosinophilic pneumonia, especially in eosinophilic granulomatosis with polyangiitis (EGPA) patients. Such exceedingly rare events were mainly described within the first months of treatment, however late onset DIBE (after 6 months) has also been detected, especially in patients dependent on systemic corticosteroids.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40728879 Combined European and Japanese criteria to diagnose eosinophilic chronic rhinosinusitis 771 773 EN T. Kumai Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan; Department of Innovative Head and Neck Cancer Research and Treatment, Asahikawa Medical University, Japan M. Kono Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan R. Sato Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan T. Terazawa Advanced Medical Engineering Research Center, Asahikawa Medical University, Japan R. Hayashi Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan T. Inoue Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan R. Wakisaka Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan H. Komatsuda Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan H. Yamaki Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan K. Ohara Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan T. Nagato Department of Pathology, Asahikawa Medical University, Japan K. Kishibe Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan Y. Takewa Advanced Medical Engineering Research Center, Asahikawa Medical University, Japan M. Takahara Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Japan 3337 10.4193/Rhin25.048 The recurrence of nasal polyps has frequently been observed with chronic rhinosinusitis with nasal polyps (CRSwNP), especially with asthma and N-ERD (NSAID-exacerbated respiratory disease). Patients with eosinophilic tissue infiltration are diagnosed as having eosinophilic chronic rhinosinusitis (ECRS), a unique CRSwNP subtype. Since the terminology of CRSwNP might include the patients with inflammatory polyps in addition to ECRS, the classification of CRSwNP by endotype is necessary to select the patients who require T2I-targeted biologic treatments. The concept of ECRS was established in 2001. However, a global consensus has not been reached regarding its definition due to the lack of standard histopathologic criteria and methodology for its classification.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40757612 Initial experience of high-fidelity 3D-printed models for training in septorhinoplasty 774 776 EN S.P. Williams Liverpool Head and Neck Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK S.L. Leong Liverpool Head and Neck Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK 3339 10.4193/Rhin25.137 Gaining the confidence needed for independent practice in septorhinoplasty remains a difficulty for surgeons in training.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40928456 Assessing the need for bed rest after anterior skull base reconstruction: insights from a multicentre retrospective observational study 777 778 EN X. Yan Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, China L. Wang Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, China J. Liu Department of Otorhinolaryngology-Head and Neck Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China H. Zhang ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China W. Wei Department of Otorhinolaryngology-Head and Neck Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China L. Yu Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, China W. Li ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China H. Yu ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China Z. Wang Department of Otorhinolaryngology-Head and Neck Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China Y. Jiang Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, China 3354 10.4193/Rhin25.123 Skull base reconstruction is a critical component of endoscopic endonasal skull base surgery (EESBS). Bed rest remains an indispensable element of post-operative care, which should be carefully considered for reducing the risk of cerebrospinal fluid (CSF) leaks and enhancing surgical outcomes (1, 2). However, the necessity of bed rest continues to be controversial as indicated by the expert consensus on perioperative management of skull base reconstruction, due to a lack of high-quality evidence to support its effectiveness (1-4). This study focuses exclusively on anterior skull base reconstruction, which is frequently employed in EESBS but has not been sufficiently investigated. In this study, we retrospectively collected patient data from three skull base centres to analyse the impact of bed rest on the occurrence of post-operative CSF leakage.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40779764 Targeting highly expressed olfactory receptors to improve olfactory testing and training 779 780 EN H. Benkhatar Centre Hospitalier de Versailles, Service d’ORL et chirurgie cervico-faciale, Le Chesnay-Rocquencourt, France J. Topin Universite Cote d'Azur, Institut de Chimie de Nice (ICN) UMR 7272, CNRS, Nice, France I. Parrot IBMM, University of Montpellier, CNRS, ENSCM, Montpellier, France; and Odore Scola, Mauguio, France S. Fiorucci Universite Cote d'Azur, Institut de Chimie de Nice (ICN) UMR 7272, CNRS, Nice, France 3340 10.4193/Rhin25.210 Olfactory testing and training constitute important foundations of diagnostic and therapeutic management of patients presenting with olfactory loss. The precise repertoire of human olfactory receptors engaged by standard odorants in olfactory detection thresholds, identification tests, and training is surprisingly under-investigated, limiting our understanding of these methods.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 41081473 The role of nasal cytology in the evaluation of candidates for olfactory implantation 781 781 EN M. Gelardi Otolaryngology and Nasal Cytology Center, Bari, Italy 3369 10.4193/Rhin25.459 I read with great interest the recent consensus document on olfactory implants. This excellent and comprehensive work represents a significant milestone in the translational pathway towards sensory neuroprostheses for patients with persistent olfactory dysfunction (OD).

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40985071 Inclusion of Chinese databases in meta-analyses on herbal medicine for rhinosinusitis 782 738 EN L.K. Zhong Otorhinolaryngology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China W.Y. Zhu Otorhinolaryngology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China L. Chen Otorhinolaryngology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China 3359 10.4193/Rhin25.358 We read with great interest the systematic review by Choulakis et al. Traditional herbal medicine in the treatment of acute and chronic rhinosinusitis. This comprehensive analysis provides valuable insights into evidence-supported herbal interventions for rhinosinusitis, particularly highlighting preparations like BNO-1016 for acute rhinosinusitis (ARS) and Xiangju for chronic rhinosinusitis (CRS). The rigorous methodology, including risk-of-bias assessments, strengthens the review’s credibility.

International Rhinologic Society Rhinology 0300-0729 63 6 2025 12 1 40988606 Answer to "Inclusion of Chinese databases in meta-analyses on herbal medicine for rhinosinusitis" 784 784 EN K. Choulakis Department of Otorhinolaryngology, General Hospital of Athens "G.Gennimatas", Athens, Greece A. Karatzanis Department of Otorhinolaryngology, University of Crete Medical School, Greece C. Skoulakis Department of Otorhinolaryngology Neurology and Sensory Organs, University of Thessaly, Greece I.M. Vlastos Department of Otorhinolaryngology, Evangelismos General Hospital of Athens, Athens, Greece E. Prokopakis Department of Otorhinolaryngology, University of Crete Medical School, Greece 3361 10.4193/Rhin25.400 We would like to sincerely thank Zhong et al. for their thoughtful and well-articulated letter in response to our recent systematic review (1). Their commentary offers interesting perspectives on the landscape of traditional herbal medicine research and the role of Chinese-language databases.