International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40855751 Rhinology and cognition 513 513 EN W.J. Fokkens Department of Otorhinolarynogology and head and neck surgery, Amsterdam University Medical Centres, Amsterdam, The Netherland 3347 10.4193/Rhin25.905 This issue of our journal starts with an extremely interesting systematic review on the impact of CRS on cognition measured with objective global cognitive function tests like the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE).

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40619980 Chronic rhinosinusitis and cognition: a systematic review and meta-analysis 514 522 EN Esther Yanxin Gao Department of Otolaryngologyâ€"Head and Neck Surgery, Sengkang General Hospital, Singapore;Department of Otolaryngologyâ€"Head and Neck Surgery, Singapore General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore Benjamin Kye Jyn Tan Department of Otolaryngologyâ€"Head and Neck Surgery, Singapore General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Surgery Academic Clinical Program, SingHealth, Singapore Kai Lin Chan Duke-NUS Medical School, Singapore Clara Xin Yi Chia Yong Loo Lin School of Medicine, National University of Singapore, Singapore Claire Jing-Wen Tan Department of Otolaryngologyâ€"Head and Neck Surgery, Sengkang General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore Brian Sheng Yep Yeo Yong Loo Lin School of Medicine, National University of Singapore, Singapore Xuandao Liu Department of Otolaryngologyâ€"Head and Neck Surgery, Singapore General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Surgery Academic Clinical Program, SingHealth, Singapore Laura Tay Department of Geriatric Medicine, Sengkang General Hospital, Singapore Ecosse L. Lamoureux Singapore Eye Research Institute, Singapore National Eye Centre, Singapore;Health Services and System Research Department, Duke-NUS Medical School, Singapore;Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Australia Neville Wei Yang Teo Department of Otolaryngologyâ€"Head and Neck Surgery, Singapore General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Surgery Academic Clinical Program, SingHealth, Singapore Tze Choong Charn Department of Otolaryngologyâ€"Head and Neck Surgery, Sengkang General Hospital, Singapore;Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Surgery Academic Clinical Program, SingHealth, Singapore 3317 10.4193/Rhin25.031 Background: Recent clinical studies have alluded to an association between chronic rhinosinusitis (CRS) and cognition, possibly mediated by local and systemic neuroinflammation. This meta-analysis seeks to clarify the association of CRS diagnosis or treatment with cognitive function and dementia. Methodology: Two blinded reviewers searched PubMed, Embase, and Scopus for studies comparing cognitive function (global/domain-specific) or dementia in patients with/without CRS or pre/post-CRS treatment. The risk of bias was assessed using ROBINS-I/ROBINS-E. Random-effects models were used to pool the ratio of means (RoM) for cognitive scores and the odds ratio (OR) for dementia. Results: From 1,149 records, 10 studies encompassing 107,610 patients were included. CRS was associated with poorer global cognitive function compared to healthy. CRS treatment was associated with improvements from baseline in processing speed and working memory. There was no significant cross-sectional association between CRS and dementia. Conclusion: CRS is associated with 9% poorer global cognitive function, while CRS treatment is associated with 8-9% improvements in processing speed and working memory. Larger longitudinal studies are needed to fully elucidate these relationships.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40720946 Rhino(septo)plasty Informed Consent. Consensus by the European Rhinoplasty Course Faculty-EUFOREA 523 533 EN P.W. Hellings Allergy and Clinical Immunology Research Unit, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium;Clinical Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium;Department of Otorhinolaryngology, Laboratory of Upper Airways Research, University of Ghent, Ghent, Belgium. D. Bertossi Unit of Maxillo Facial Surgery Head and Neck Department, Università degli Studi di Verona, Verona, Veneto, Italy. C. Cingi Department of Otorhinolaryngology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir/Turkey. S. Claeys Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium. J. Constantinidis 1st Academic Otolaryngology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Kiriakidi 1 Str, 546 21, Thessaloniki, Greece. D.M. Conti The European Forum for Research and Education in Allergy and Airway Diseases Scientific Expert Team Members, Brussels, Belgium;Escuela de Doctorado UAM, Centro de Estudios de Posgrado, Universidad Autónoma de Madrid. Calle Francisco Tomás y Valiente, nº 2. Ciudad Universitaria de Cantoblanco, 28049 Madrid, Spain. A. D'Souza Department of Head and Neck, Facial Plastic and Reconstructive Surgeon, University Hospital Lewisham, London, United Kingdom. F. Declau Department of ENT, Head and Neck Surgery, GZA-ziekenhuizen, Campus Sint-Vincentius, Antwerp, Belgium;Department of ENT, Head and Neck Surgery, Antwerp University School of Medicine and Health Sciences, Antwerp, Belgium. H. Foda Department of Otolaryngology, Alexandria Medical School, Alexandria, Egypt. W. Fokkens Department of Otorhinolarynogology and head/neck surgery, Amsterdam University Medical Centres, location AMC, University of Amsterdam, Amsterdam, The Netherlands. P. Gevaert Department of Otorhinolaryngology, Laboratory of Upper Airways Research, University of Ghent, Ghent, Belgium. W. Gubisch Department of Facial Plastic Surgery, Marienhospital Stuttgart, Boeheimstrasse 37, 70199, Stuttgart, Germany. S. Halewyck Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium. G. Lekakis Department of Otorhinolaryngology Head and Neck Surgery, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium;Department of Otorhinolaryngology Head and Neck Surgery, Regional Hospital Tienen, Flanders, Belgium. G. Liva Department of Otorhinolaryngology, University of Crete, School of Medicine, Heraklion, Greece. A. Mesbahi Facial Plastic Surgery Clinic, Fars Province, Shiraz, Iran. C. Mcintosh Facial Plastic Surgery, Edge Day Hospital, Port Elizabeth, South Africa. G. Nolst Trenité Jan van Goyen Medical Center, Amsterdam, the Netherlands. V. Picavet ENT, Praxis für Ästhetik/HNO, Ludwigstrasse 7, Augsburg, Bavaria, Germany;ENT, MVZ Moser Gehrking Sauter und Partner, Augsburg, Bavaria, Germany;ENT Praxis Hasselbacher-Picavet E. Prokopakis Department of Otorhinolaryngology, University of Crete, School of Medicine, Heraklion, Greece. E. Robotti Department of Plastic Surgery, Villa Sant'Apollonia Private Health Clinic, Bergamo, Lombardia, Italy. S. Vandenbroeck Department of Otorhinolaryngology Head and Neck Surgery, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium;Department of Otorhinolaryngology Head and Neck Surgery, Regional Hospital Tienen, Flanders, Belgium. A. Van Hoolst Department of Otorhinolaryngology Head and Neck Surgery, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium;Department of Otorhinolaryngology Head and Neck Surgery, Regional Hospital Leuven, Flanders, Belgium T. Vansweevelt Faculty of Law, University of Antwerp, Antwerp, Belgium. W. Wagner Municipal Hospital of Munich, Munich, Germany. Kölner Platz 1, 80804 Munich. 3295 10.4193/Rhin24.204 Background: Patients seeking rhino(septo)plasty need to be adequately informed by their surgeon or surgical team members about the procedure, the expected outcomes, complication risks and post-operative care, and the available alternatives. A consensus on the content of an informed consent in rhino(septo)plasty is currently lacking despite the high unmet need. Methodology: The extended international faculty of the European Rhinoplasty Course in Brussels organized by EUFOREA has generated an overview of the current literature on rhinoplasty outcomes and complication rates, and available informed consents. A proposal for informed consent was elaborated, consensus reached and checked for legal validity. Results: An overview of reported outcomes and complication rates of rhino(septo)plasty are provided. Additionally, contents of existing consent forms for rhino(septo)plasty surgery are compared with requirements found in literature on informed consent, leading to a proposal of informed consent including relevant information according to expert consensus. Conclusions: An informed consent form for rhino(septo)plasty is proposed by the international faculty of the European Rhinoplasty Course, that might serve rhinoplasty surgeons in the development of their informd consent documents.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40614254 Current concepts in sinonasal tumors: from pretherapeutic assessment to patient-tailored treatment 534 542 EN C.M. Meerwein Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital and University of Zurich, Switzerland T. Mauthe Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital and University of Zurich, Switzerland M.B. Soyka Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital and University of Zurich, Switzerland D. Holzmann Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital and University of Zurich, Switzerland 3316 10.4193/Rhin25.073 Background: Managing sinonasal malignancies requires a thorough oncological assessment and interdisciplinary collaboration. Patients often present at an advanced tumor stage with a delay in diagnosis. With the recent advancements in imaging techniques along with the growth in molecular testing knowledge, the landscape of these tumors has become increasingly diverse. The pretreatment assessment must include information gathered from radiological and pathological evaluations, as well as intraoperative exploration of the tumors. Only a comprehensive approach allows a personalized treatment plan. Methodology: This narrative review synthesizes current evidence, encompassing pretherapeutic evaluations and the development of individualized treatment protocols. Results: Multimodal treatment strategies, including surgical resection, radiotherapy (RT), chemotherapy, and immunotherapy (for sinonasal mucosal melanoma) need to be tailored based on tumor histology, stage, and patient-specific factors. Endoscopic surgical approaches demonstrated oncologic outcomes comparable to traditional open techniques, with reduced perioperative morbidity. Neoadjuvant therapies facilitated improved local control and organ preservation in advanced-stage tumors. Conclusion: Ongoing advancements in imaging, surgical interventions, as well as (neo)adjuvant therapies have significantly improved the prognostic landscape of sinonasal malignancies. A multidisciplinary, personalized treatment approach remains pivotal in optimizing patient outcomes.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40728905 Negative pressure drainage vs. nasal packing after septoplasty: a randomized clinical trial 543 550 EN Y. Tu Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China T. Jiang Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China G. Zhao Qingdao Caretaker Otolaryngology Head and Neck Surgery Hospital, Qingdao, China L. Xiao Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China L. Shi Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China F. Zhong Department of Nursing, Shandong Second Provincial General Hospital, Jinan, China A. Chen Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China 3338 10.4193/Rhin25.112 Background: Negative pressure drainage is a commonly used method in surgery, but studies applying negative pressure drainage in septoplasty are relatively few. Methodology: A randomized clinical trial was conducted to compare negative pressure drainage and nasal packing after septoplasty. Patients with nasal septal deviation underwent septoplasty from November 2023 to March 2024 were enrolled. Symptom scores and quality of life scores were assessed on postoperative day 1, day 5, and at 1 month to evaluate postoperative comfort. Results: A total of 95 patients completed the study, the median (IQR) age was 29 (21, 43) years, and 73 (77%) identified as male. 48 (51%) patients were randomized to nasal packing group and 47 (49%) to negative pressure group. On postoperative day 1, the negative pressure group showed significantly lower symptom scores for nasal congestion, rhinorrhea, olfactory dysfunction, headache, eye discomfort, ear fullness, and better quality of life compared to the packing group. On postoperative day 5, the negative pressure group showed significantly lower scores for olfactory dysfunction and ear fullness compared to the packing group. There was no significant difference in effective rate and postoperative complications rate between negative pressure group and packing group. The cost-effectiveness ratio for the negative pressure group was significantly lower than the packing group. Conclusions: Negative pressure drainage after septoplasty significantly improves postoperative comfort in the first days after surgery, without affecting surgical efficacy or safety, and helps reduce medical costs.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40587156 A prospective cohort study comparing the effects of different middle turbinate treatments on olfactory function recovery in CRSwNP patients after FESS 551 564 EN F. Jian E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China;Department of Otorhinolaryngology, Shenzhen Children's Hospital, Shenzhen, Guangdong, China J. Lao E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China R. Ge E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China Q. Yang E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China S. Wu E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, People’s Republic of China 3310 10.4193/Rhin24.320 Background: The factors affecting postoperative olfactory recovery in chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. This study explores postoperative pathological classification and the impact of different middle turbinate management strategies on olfactory recovery. Methodology: Seventy-two CRSwNP patients undergoing functional endoscopic sinus surgery (FESS) with ≥6 months follow-up were classified into eosinophilic (ECRSwNP) and non-eosinophilic (nECRSwNP) groups. Based on middle turbinate management, patients were further divided into resection (partial/complete) and preservation groups. Olfactory scores, clinical characteristics, and nasal endoscopy findings were analyzed, and multifactorial analysis identified factors influencing olfactory recovery. Results: TDI scores in the ECRSwNP group remained lower than those in the nECRSwNP group preoperatively and postoperatively. However, olfactory score improvement and the proportion of significantly improved patients did not differ significantly between the two groups. Middle turbinate management was associated with greater olfactory improvement, particularly in nECRSwNP patients. Although the complete middle turbinate resection group had lower preoperative olfactory scores than the partial resection group, no significant difference was observed in postoperative olfactory improvement between the two approaches.Higher preoperative polyp scores and middle turbinate management predicted olfactory improvement. Conclusions: FESS significantly improves the olfactory function in CRSwNP patients, and the extent of olfactory improvement is independent of pathological type. Patients with higher preoperative Lildholdt polyp scores and those who underwent middle turbinate management during FESS were more likely to exhibit improved olfactory function at 6 months postoperatively.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40587119 Endoscopic surgery versus conservative treatment in nasopharyngeal carcinoma patients with nasopharyngeal necrosis 565 575 EN Y-F. Ouyang Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China;Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China Q-L. Lin Department of Radiation Oncology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, China A-C. Li Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China; College of Clinical Medicine, Fujian Medical University, Fuzhou, , China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, , China J-Y. Song Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian province, China R-L. Xie Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China;Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China 3308 10.4193/Rhin24.403 Background: Nasopharyngeal necrosis is a common sequela after treatment for nasopharyngeal carcinoma (NPC). This study aims to compare the effectiveness of the main interventions, endoscopic surgery and conservative therapy, on nasopharyngeal necrosis and identify potential beneficiaries. Methodology: This retrospective study was conducted on patients with nasopharyngeal necrosis from September 2008 to December 2020 at the Cancer Hospital of Sun Yat-sen University. The overall survival (OS) of patients with nasopharyngeal necrosis and their mucosal healing status were assessed. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance confounding factors between the two groups. Results: A total of 517 patients (124 females; 393 males) with nasopharyngeal necrosis were included in this analysis, among whom 287 received conservative therapy and 230 underwent endoscopic surgical treatment. In the unmatched cohort, the endoscopic surgery group had a higher 3-year OS rate than the conservative therapy group. Patients who underwent surgery had higher cure rates than did those who received conservative therapy. PSM and IPTW analyses yielded similar results. Multivariate analyses of the unmatched, PSM, and IPTW cohorts revealed that nasal endoscopic surgery was an independent protective factor for the OS of patients with nasopharyngeal necrosis. Conclusions: In this retrospective research, endoscopic surgery demonstrated better efficacy than conservative therapy for nasopharyngeal carcinoma patients with nasopharyngeal necrosis, while conservative therapy may be preferred for patients with superficial mucosal necrosis.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40587220 Seasonality in the incidence of acute sinusitis, air pollutant levels, and climate 576 583 EN S-H. Hung Department of Otolaryngology, Taipei Medical University, Taipei, Taiwan;Department of Otolaryngology, Wan Fang Hospital, Taipei, Taiwan;International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Y-F. Cheng Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Otorhinolaryngology, National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan;Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan;Research Center of Data Science on Healthcare Industry, College of Management, Taipei, Taiwan H-C. Lin School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan;Research Center of Sleep Medicine, Taipei Medical University Hospital, Taipei, Taiwan C-S. Chen Research Center of Data Science on Healthcare Industry, College of Management, Taipei, Taiwan;School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan;Research Center of Sleep Medicine, Taipei Medical University Hospital, Taipei, Taiwan;Department of Public Finance, Public Finance and Finance Research Center, National Taipei University, Taipei, Taiwan 3311 10.4193/Rhin25.054 Introduction: Emerging evidence from epidemiological studies highlights the interaction between air quality metrics and sinusitis occurrence. This study investigates the relationship between acute sinusitis incidence, air pollutant levels, and climatic conditions in Taiwan from 2008 to 2017. Methods: This study extracted outpatient claims data from the Longitudinal Health Insurance Database 2010. We computed seasonal incidence rates of acute sinusitis episodes per 1000 population over 120 months, stratifying the data by gender and three age groups: 20-44, 45-64, and 65 years and older. Addressing the seasonal variability inherent in our dataset, we utilized Auto-Regressive Moving Average (ARMA) models to analyze each variable as a univariate time series influenced by its historical values. Results: The analysis reveals that, except relative humidity, all other climatic factors including CO, NO2, SO2, PM10, O3, ambient temperature and rainfall demonstrated significant crude correlations with the rates of acute sinusitis. The ARIMA test suggested that seasonality plays a significant role in influencing sinusitis episodes across all age groups. Specifically, individuals experience significantly higher incidence rates during winter compared to spring. These findings underscore winter as a period with notably higher incidence rates of acute sinusitis, even after adjusting for meteorological and air pollution variables. Conclusions: This study provides comprehensive evidence of the significant associations between acute sinusitis incidence, air quality, and climatic factors in Taiwan.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40674772 Establishing validity of a novel patient-centered and directly measurable definition of acute exacerbation of chronic rhinosinusitis 584 590 EN F.A. Houssein Department of Otolaryngologyâ€"Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA A.R. Sedaghat Department of Otolaryngologyâ€"Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA K.M. Phillips Department of Otolaryngologyâ€"Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA 3330 10.4193/Rhin24.378 BACKGROUND A patient-centered and directly measurable definition for acute exacerbation of chronic rhinosinusitis (AECRS) has been developed as “a flare up of symptoms beyond day-to-day variation, lasting at least 3 days, and to which a distinct negative impact on a patient’s quality of life (QOL) or functionality can be attributedâ€�. Our aim is to understand how this definition correlates with previously used metrics. METHODOLOGY: Cross-sectional study of chronic rhinosinusitis (CRS) patients. The number of AECRS (using this novel definition), courses of CRS-related systemic antibiotics and corticosteroids taken for these AECRS, and number of asthma exacerbations in the past 6 months was queried. Disease-specific quality of life was measured using the 22-item Sinonasal Outcome Test. RESULTS: A total of 237 CRS patients were enrolled. In the 6-month period prior to study enrollment, the mean number of AECRS was 4.2 while the mean number of systemic antibiotics or corticosteroids taken for these AECRS was 1.6 reflecting patients received rescue medication for 33% of AECRS. The number of AECRS was weakly correlated with number of systemic rescue medications and SNOT-22 score. For asthmatic CRS patients, numbers of AECRS and asthma exacerbations were correlated. Finally, comorbidities were associated with higher AECRS frequency by 29% in migraine and 41% in active tobacco users. CONCLUSIONS: We achieved our aim by showing the AECRS definition correlates with systemic rescue medication usage, disease-specific QOL and asthma exacerbations. Our results demonstrate that indirect measures of AECRS may not capture all AECRS. Furthermore, comorbid migraine and tobacco use are associated with AECRS frequency.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40621839 Multi-centric real-world effectiveness of mepolizumab in severe chronic rhinosinusitis with nasal polyps in Germany 591 599 EN F. Bärhold Center for Rhinology and Allergology, Wiesbaden, Germany;Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Germany J. Hagemann Center for Rhinology and Allergology, Wiesbaden, Germany L. Klimek Center for Rhinology and Allergology, Wiesbaden, Germany P. Huber Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig Maximilian University of Munich, Munich, Germany M. Gröger Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig Maximilian University of Munich, Munich, Germany A.G. Loth Department of Otorhinolaryngology, Goethe University Frankfurt, University Medical Center, Frankfurt am Main, Germany B.P. Ernst Department of Otorhinolaryngology, Goethe University Frankfurt, University Medical Center, Frankfurt am Main, Germany C. Beutner Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany T. Dombrowski Department of Otolaryngology, Head and Neck Surgery, University Medical Center Georg-August-University, Göttingen, Germany U. Förster-Ruhrmann Department of Otorhinolaryngology, Charité-Universitätsmedizin, Berlin, Germany H. Olze Department of Otorhinolaryngology, Charité-Universitätsmedizin, Berlin, Germany M. Cuevas Department of Otolaryngology, Head and Neck Surgery, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany N. Gunder Department of Otolaryngology, Head and Neck Surgery, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany J. Malanda Department of Otorhinolaryngology, Head and Neck Surgery, Kiel University, University Medical Centre Schleswig-Holstein, Kiel, Germany M. Laudien Department of Otorhinolaryngology, Head and Neck Surgery, Kiel University, University Medical Centre Schleswig-Holstein, Kiel, Germany T. Albrecht Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Germany C. Matthias Department of Otolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany S. Becker Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Germany 3319 10.4193/Rhin25.104 BACKGROUND: Within the last years, monoclonal antibodies (biologicals) have revolutionized the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly improved symptom control in otherwise refractory cases. The effectiveness of the biological mepolizumab, an IL-5 receptor antibody, has not yet been investigated extensively. This multi-centric study assesses its impact on a large German patient cohort including biological naïve and switched patients. METHODOLOGY: In this retrospective multi-centric study, patients with the diagnosis of severe CRSwNP treated with mepolizumab by German tertiary referral centers were included. Data were collected retrospectively from patient records. The change from baseline regarding patient reported symptom control, serum biomarkers, nasal polyp score (NPS), and sense of smell were analysed over a course of up to 30 months. RESULTS: 96 patients from 8 tertiary treatment centers were included, 36.5% female, with a mean age of 54.1±14.3 years. Patient reported outcome measures, smell, and NPS improved significantly within 6 months after treatment initiation or switch from a different biological to mepolizumab. Change from baseline in outcome parameters was smaller in the switch-group, whereas comorbid asthma indicated greater treatment success. CONCLUSIONS: Our real-world data show a sustained therapeutic effect of mepolizumab in CRSwNP, including a large proportion of patients who were previously treated with a different biological. This study is the largest real-world cohort to date depicting realistic treatment and disease situations, confirming a broad range of indication for mepolizumab in severe CRSwNP.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40657706 Antimicrobial activity of simvastatin against chronic rhinosinusitis-related Staphylococcus aureus: an in vitro study 600 607 EN S.P. Goldie School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Department of Otorhinolaryngology / Head and Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom L.P. Lau School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom H.A.S Jones Department of Otorhinolaryngology / Head and Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom P.G. Harries Department of Otorhinolaryngology / Head and Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom A.F. Walls School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom R.J. Salib School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;Department of Otorhinolaryngology / Head 3323 10.4193/Rhin25.023 INTRODUCTION: Staphylococcus aureus (S. aureus) in chronic rhinosinusitis (CRS), particularly when localised intracellularly, is linked to disease recalcitrance and poor post-surgical outcomes. Antibiotics frequently fail to penetrate the mammalian cell membrane, resulting in an inability to address the intracellular component of S. aureus. This contributes to treatment failure and development of antimicrobial resistance. We investigated the antimicrobial effects of simvastatin, a widely used, inexpensive medication with extracellular and intracellular antimicrobial properties, against CRS-related S. aureus. METHODS: Simvastatin’s antimicrobial activity, in prodrug and hydroxy acid forms, was assessed against S. aureus using the broth dilution method to determine the minimal inhibitory concentration (MIC). Intracellular activity of simvastatin was evaluated by pre-treating S. aureus-infected LAD2 mast cells with simvastatin and performing colony forming unit (CFU) enumeration and confocal microscopy. Cell viability was assessed using lactate dehydrogenase (LDH) assays. RESULTS: Simvastatin exhibited an extracellular MIC of 40 mmol/l against S. aureus. Intracellularly, it significantly reduced the bacterial burden by 46-fold in a dose-dependent manner between concentrations of 0.1-100 mmol/l. Toxicity to LAD2 cells was observed at 100 mmol/l. Confocal microscopy revealed a lower percentage of infected cells in the group pretreated with 30 μmol/l simvastatin (15.3%) compared to untreated cells (32.8%). Simvastatin hydroxy acid demonstrated no antimicrobial activity against S. aureus. CONCLUSIONS: Simvastatin demonstrates in vitro antimicrobial activity against CRS-related S. aureus with the potential for repurposing as a novel antibiotic-sparing topical agent for the treatment of refractory CRS. This could improve surgical outcomes andreduce the risk of antimicrobial resistance.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40657797 Intranasal trigeminal and secretory functions are impaired after topical anaesthesia or surgical treatment of epistaxis 608 615 EN J.J. Vavrina Department of Otorhinolaryngology Head and Neck Surgery, University of Zurich and University Hospital Zurich, Zurich, Switzerland T. Hummel Interdisciplinary Center Smell and Taste, Department of Otorhinolaryngology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany B.N. Landis Rhinology-Olfactology Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland S. Macario Department of Otorhinolaryngology Head and Neck Surgery, University of Zurich and University Hospital Zurich, Zurich, Switzerland;Rhinology-Olfactology Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland M.B. Soyka Department of Otorhinolaryngology Head and Neck Surgery, University of Zurich and University Hospital Zurich, Zurich, Switzerland 3325 10.4193/Rhin24.314 BACKGROUND: The sphenopalatine artery (SPA) runs in close proximity to the branches of the trigeminal nerve and to the sympathetic and parasympathetic secretomotor fi bers. In refractory epistaxis, monopolar cautery of the SPA during surgery is of widespread use. The eff ect of coagulation on adjacent trigeminal and parasympathetic branches, and thus intranasal sensitivity and secretory function, is unknown. METHODS: To investigate intranasal trigeminal function (INTF) by means of CO2 stimuli intranasally, at baseline and after decongestion, before and after local anaesthesia (xylocaine) in healthy subjects and after monopolar cautery in patients treated for refractory epistaxis. In the latter, INTF and secretory function were tested by comparing the treated with the untreated side. Nasal and lacrimal secretions were measured with intranasal sponges and Schirmer’s tests. SETTING: Monocentric cohort study in tertiary referral centre. RESULTS: A total of 37 healthy participants and 17 patients were included. Nasal decongestion had no eff ect on CO2 measurements, whereas local anaesthesia signifi cantly decreased INTF in healthy subjects. In patients, the operated side showed signifi cantly lower INTF, lower nasal secretory function but no signifi cant changes in lacrimal function.CONCLUSION: Local anaesthesia and surgical treatments have measurable eff ects on INTF. Monopolar cautery of the SPA and its branches aff ects nasal secretory function. These eff ects may lead to symptoms and surgeons should be aware of the potential harm in epistaxis treatments.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40820310 The NSUN2-YBX1 axis enhances 5-Methylcytosine modification to facilitate NPM1-mediated nuclear translocation of PKM2, augmenting the Warburg effect and promoting nasopharyngeal carcinoma progression in a mouse model 616 627 EN Z. Wang Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China X. Chen Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China S. Wu Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China B. Liao Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China L. Guo Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China Y. Liu Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China T. Zhou Department of Thyroid Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, P.R. China 3332 10.4193/Rhin24.496 Background: Nasopharyngeal carcinoma (NPC) is notable not only for its distinct geographic and ethnic distribution but also for its metabolic alterations. A key feature of NPC is its reliance on aerobic glycolysis for energy production. This shift from oxidative phosphorylation to glycolysis provides cancer cells with a metabolic advantage, supporting rapid growth and survival. Targeting aerobic glycolysis has therefore emerged as a promising therapeutic strategy. Methods: RT-qPCR, Western blot, IHC, and IF staining were used to examine gene and protein expression levels. Cell viability, proliferation, migration, and invasion were measured using the CCK-8 assay, colony formation assay, and transwell assay, respectively. Interactions among NPM1, PKM2, NSUN2, and YBX1 were examined using RIP, Co-IP, MeRIP, RNA pulldown, and dual-luciferase reporter assays. Aerobic glycolysis and oxidative phosphorylation (OXPHOS) levels were analyzed using the XF96 metabolic analyzer. Additionally, an in vivo mouse model of NPC was established for further validation. Results: NPM1 was abnormally elevated in NPC tissues and cells. Silencing of NPM1 inhibited aerobic glycolysis, suppressed NPC progression and metastasis, and reduced PKM2 nuclear translocation. Mechanistically, NPM1 physically interacted with PKM2 to promote its nuclear localization, while the NSUN2/YBX1 axis upregulated NPM1 expression through m5C modification, stabilizing NPM1 mRNA. Conclusion: The NSUN2-YBX1 axis induces m5C modification of NPM1, leading to increased NPM1 stability and its expression. This upregulation facilitates the nuclear translocation of PKM2, which promotes aerobic glycolysis and drives the proliferation and metastasis of NPC. These findings highlight the potential of targeting NPM1 as a novel therapeutic approach for NPC.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40820301 ITGAM and FCGR3B contribute to recurrent and limited CRSwNP in children through phagosome pathway 628 638 EN X. Xiao Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China X. Chen Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China W. Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China N. Zhang Department of Pathology, Beijing Childrens Hospital, Capital Medical University, National Centre for Childrens Health, Beijing, China C. Jia Department of Pathology, Beijing Childrens Hospital, Capital Medical University, National Centre for Childrens Health, Beijing, China J. Wei Clinical Research Center, National Center for Childrens Health, Beijing Childrens Hospital, Capital Medical University, Beijing, China J. Chen Beijing Engineering Research Center of Pediatric Surgery, Engineering and Transformation Center, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China J. Zhao Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China X. Yao Department of Pathology, Beijing Childrens Hospital, Capital Medical University, National Centre for Childrens Health, Beijing, China X. Kang Department of Pathology, Beijing Childrens Hospital, Capital Medical University, National Centre for Childrens Health, Beijing, China T. Wang Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China L. Tang Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China X. Yang Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China W. Zhang Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China C. Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China P. Wang Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China W. Ge Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China; Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China; Department of Otolaryngology, Head and Neck Surgery, National Clinical Research Center for Respiratory Diseases, Beijing Childrens Hospital Y. Han Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China 3334 10.4193/Rhin25.035 Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is more common in children with limited CRSwNP (L-CRSwNP). L-CRSwNP shares similar clinical phenotypes with recurrent CRSwNP (R-CRSwNP). This study aimed to explore the molecular mechanisms of L- and R-CRSwNP in children. Methodology: Compared clinical characteristics and RNA sequencing data of 20 L-CRSwNP and 5 R-CRSwNP in children. Paired analyzed RNA sequencing data of 6 children with L-CRSwNP polyps and mucosal tissue samples. Conducted GO and KEGG enrichment analyses. Identified hub genes through protein-protein interaction networks (PPI). Validated hub genes in L- and R-CRSwNP using real-time quantitative PCR (RT-qPCR), immunohistochemistry (IHC), and multiplex immunohistochemistry (mIHC). Results: RNA-seq analysis of L- and R-CRSwNP polyp showed no differentially expressed genes (DEGs). RNA-seq paired analysis of L-CRSwNP identified 1419 DEGs. GO enrichment analysis showed significant enrichment for biological processes associated with neutrophils. ITGAM and FCGR3B were identified as hub genes by PPI analysis. RT-qPCR and IHC results suggested the expression levels of ITGAM and FCGR3B were significantly increased in L- and R-CRSwNP. mIHC results suggested ITGAM and FCGR3B were closely associated with neutrophils and M2 macrophages in L- and R-CRSwNP. Conclusions: L- and R-CRSwNP in children exhibit similar clinical phenotypes and molecular mechanisms. ITGAM and FCGR3B are hub genes contributing to disease through neutrophil- and M2 macrophage-mediated phagosome pathway.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40587092 Comment to the article "Comparison of outcomes for Draf IIB vs Draf III in endoscopic frontal sinus surgery: a comprehensive systematic review and meta-analysis" 639 639 EN A. Kacprzyk Department of Otorhinolaryngology, Ludwik Rydygier Memorial Hospital, Kraków, Poland R. Głowacki Department of Otorhinolaryngology, Ludwik Rydygier Memorial Hospital, Kraków, Poland 3309 10.4193/Rhin25.171 We read with great interest the article by Hirayama et al. (1) and commend the authors on their comprehensive work, which presents an extensive dataset accompanied by robust statistical analyses and a detailed systematic review. This study is undoubtedly a significant contribution to the literature on frontal sinus surgery.

International Rhinologic Society Rhinology 0300-0729 63 5 2025 10 1 40587092 Response to: Comment to the article "Comparison of outcomes for Draf IIB vs Draf III in endoscopic frontal sinus surgery: a comprehensive systematic review and meta-analysis" 640 640 EN M.S. Shahid Aga Khan University, Aga Khan University Hospital, Karachi, Sindh, Pakistan Y. Hirayama Department of Otolaryngology, University Hospitals Birmingham, NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom H. Iftikhar Department of Otolaryngology, University Hospitals Northamptonshire, Cliftonville, Northampton, United Kingdom 3320 10.4193/Rhin25.233 We thank our readers for their interest in our work and their thoughtful comments. We concur with the concerns raised regarding the heterogeneity of the included studies, which we have openly acknowledged and discussed in the limitations section of our review.