International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37772643 The sweet smell of rhinology 385 385 EN B.N. Landis University of Geneva, Geneva, Switzerland 3113 10.4193/Rhin23.905

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37453134 Preoperative, technical, and postoperative considerations for skull base reconstruction: a practical review of critical concepts 386 403 EN K.M. Phillips Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA M.T. Turner Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, WV, USA E.C. Kuan Departments of Otolaryngology-Head and Neck Surgery and Neurological Surgery, University of California, Irvine, CA, USA 3093 10.4193/Rhin23.127 Despite widespread adoption and advances in endoscopic skull base surgery, with expanding indications and the ability to effectively treat larger and more complex pathologies, skull base reconstruction following tumor resection and prevention of cerebrospinal fluid leak remains a challenge for even the most seasoned of surgical teams. Mounting evidence in all areas have pushed our understanding of skull base reconstruction principles forward. In this narrative review, we summarize critical concepts and provide practical but comprehensive guiding principles on preoperative, intraoperative/technical, and postoperative management principles related to optimizing skull base reconstructive success. The goal is to provide an informative resource for skull base surgeons (both otolaryngologists and neurosurgeons) to reference regarding state-of-the-art evidence surrounding this ever-evolving topic.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37453136 Intranasal insulin â€" effects on the sense of smell 404 411 EN B. Sienkiewicz-Oleszkiewicz Department of Clinical Pharmacology, Faculty of Pharmacy, Wroclaw Medical University, Poland and Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany A. Oleszkiewicz Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany and Institute of Psychology, University of Wroclaw, WrocÅ‚aw, Poland M.A. Bock Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany and Departamento de Salud Pública ORL, Hospital General Barrio Obrero, Asunción, Paraguay T. Hummel Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany 3094 10.4193/Rhin23.036 Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and antiapoptotic effects. It prevents energy failure and has regenerative properties, affects neuro-regeneration and counteracts insulin resistance. Hence, insulin has been suggested for various pathological states including neurocognitive disorders, obesity, and as a therapeutic option for smell loss. A sharply increased prevalence of olfactory dysfunction was observed due to the COVID-19 pandemic. The pandemic also emphasized the lack of therapeutic options for smell loss. Intranasal insulin administration has therefore been suggested to serve as potential treatment, influencing the regenerative capacities of the olfactory mucosa. This narrative review summarizes current knowledge on possible effects of intranasal insulin on the sense of smell.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37338824 Complications to acute bacterial rhinosinusitis in children - a prospective study; bacterial cultures, virus detection, allergy sensitization and immunoglobulins 412 420 EN S. Hultman Dennison Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden A. Granath Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden M. Holmström Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden P. Stjärne Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden O. Hertting Pediatric Infectious Diseases, Astrid Lindgren Children´s Hospital, Karolinska University Hospital, Stockholm, Sweden and Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden 3089 10.4193/Rhin22.168 Background: Prospective studies of complications due to acute rhinosinusitis are lacking, bacterial cultures are hard to obtain and the role of airborne allergies, viruses and immunoglobulin levels are unclear. The aim was to investigate the role of bacteria, viruses, allergy and immunoglobulins in children hospitalized due to rhinosinusitis. Methodology: A prospective cohort study in Stockholm, Sweden, of children up to 18 years of age, hospitalized due to acute bacterial rhinosinusitis, from April 1st, 2017 to April 1st, 2020. Results: Of 55 children included, 51% had a positive viral nasopharyngeal PCR and 29% had a positive allergy sensitization test. A higher percentage of middle meatus cultures were positive for bacterial growth compared to nasopharyngeal and displayed a wider array of bacteria. Dominating bacteria were S. milleri in surgical (7/12 cases), S. pyogenes in middle meatus (13/52 cases), and S. pyogenes and H. influenza in nasopharyngeal cultures (8/50 cases respectively). Nasal cultures were negative in 50% of surgical cases. An association was found between S. pyogenes and peak CRP; H. influenzae and peak CRP; S. pneumoniae and peak CRP; and possibly between M. catarrhalis and days of IV antibiotics. Further, an association between influenza A/B and S. pyogenes; a positive viral PCR and lower grade of complication and peak CRP; and a possible association between influenza virus and lower grade of complication. Allergy sensitization was possibly associated with a higher number of days with IV antibiotics. No immunoglobulin deficiencies were found. Conclusions: There seem to be differences in the patterns of bacterial growth in nasopharyngeal, middle meatus and surgical cultures in children with complications to acute bacterial rhinosinusitis. Presence of certain viruses and sensitization to airborne allergies seem to play a role in complications to acute bacterial rhinosinusitis in children.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37475674 Septoplasty and/or inferior turbinoplasty produce significant improvements of the sense of smell 421 431 EN P. Mackers Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; and Otorhinolaryngology Department, Hospital del Mar, Barcelona, Catalonia, Spain M.J. Rojas-Lechuga Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain C. Langdon Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; and Otorhinolaryngology Department, Hospital Sant Joan de Deu, Barcelona, Catalonia, Spain A. Nogués Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; and Otorhinolaryngology Department Consorci Sanitari Alt Penedès Garraf. Barcelona, Catalonia, Spain J. Mullol Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; and Clinical and Experimental Respiratory Immunollergy, IDIBAPS, Barcelona, Catalonia, Spain; and CIBER of Respiratory Diseases (CIBERES), Health Institute Carlos III, Spain I. Alobid Rhinology and Skull Base Units, Smell Clinic, Otorhinolaryngology Department Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; and Clinical and Experimental Respiratory Immunollergy, IDIBAPS, Barcelona, Catalonia, Spain; and CIBER of Respiratory Diseases (CIBERES), Health Institute Carlos III, Spain; and Unidad Alergo Rino, Centro Médico Teknon, Barcelona, Catalonia, Spain 3098 10.4193/Rhin22.461 Background: Patients with septal deviation and/or turbinal hypertrophy may experience olfactory disfunction (OD). The aim of this study was to analyse the effect of septoplasty and/or turbinoplasty on both lateralized and bilateral olfactory function. Methodology: Prospective study of 47 patients with nasal obstruction secondary to septal deviation and/or turbinal hypertrophy and 20 healthy controls. The Barcelona Olfactory test (BOT-8), a new supraliminal orthonasal subjective olfactometry, was applied 3 times in a row (in each nostril separately and in both simultaneously). The 8 items were applied randomly to minimize the possible risk of learning. The test has not established the minimal clinically important difference (MCID). Anterior rhinomanometry and acoustic rhinometry were performed. All participants self-assessed smell loss and nasal obstruction using a visual analogue scale (VAS) and completed questionnaires for nasal obstruction (Nasal Obstruction Symptom Evaluation, NOSE) and for quality of life (QoL), using disease-specific (SinoNasal Outcome Test-22, SNOT-22) and generic (Short Form-12 Health Survey, SF-12) questionnaires. Nasal measurements and questionnaires were performed preoperatively and 12 months after surgery. Results: Before surgery, patients reported worse VAS on smell loss and on nasal obstruction compared to controls. Patients scored lower BOT-8 than controls. Lateralized preoperative olfactory function showed that all BOT-8 characteristics were lower at the narrow side than the wider one. Smell function and QoL improved significantly one year after surgery. Conclusions: Nasal septal deviation and turbinal hypertrophy lead to an olfactory impairment on the obstructed nostril. Nasal surgery provides a positive outcome on olfactory function, as well as on subjective and objective outcomes.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37243721 Clinical characteristics and associated factors of qualitative olfactory dysfunction 432 440 EN T-S. Eo Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea H.Y. Lee Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea H-J. Cho Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea J-H. Yoon Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; The Korea Mouse Sensory Phenotyping Center, Yonsei University College of Medicine, Seoul, Republic of Korea M-S. Rha Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea C-H. Kim Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; The Korea Mouse Sensory Phenotyping Center, Yonsei University College of Medicine, Seoul, Republic of Korea;Taste Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea 3081 10.4193/Rhin23.004 BACKGROUND: Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD. METHODS: Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia. RESULTS: Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia. CONCLUSIONS: Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37000430 Menstrual cycle-modulated intrinsic connectivity enhances olfactory performance during periovulatory period 441 448 EN Y-T Chao Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan T-Y Hong Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan; Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan J-C Hsieh Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan; Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Intelligent Drug System 3071 10.4193/Rhin22.472 BACKGROUND: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance. METHODOLOGY: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle. RESULTS: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule. CONCLUSIONS: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37334730 Patients with olfactory loss exhibit pronounced adaptation to chemosensory stimuli: an electrophysiological study 449 455 EN Z. Li Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany R. Salloum Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany T. Hummel Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany 3088 10.4193/Rhin23.049 Background: Pronounced chemosensory adaptation affects many patients with olfactory loss. The study aimed to investigate adaptation to olfactory and trigeminal nasal stimuli in patients with olfactory loss in comparison to controls using electrophysiological measures. Methodology: Thirty-four patients with olfactory loss (mean age ± SD = 59 ± 16 years) and 17 healthy volunteers (mean age ± SD = 50 ± 14 years) were recruited. Sniffin’ sticks test was used for evaluation of olfactory function and EEG-derived chemosensory event-related potentials were recorded. Intranasal stimuli were presented using high-precision, computer-controlled stimulators based on the principles of air-dilution olfactometry. Data were analyzed in two different approaches according to the relatively short or long inter-stimulus interval. A decreased peak amplitude or a prolonged latency was considered as an expression of adaptation. Results: The majority of participants (88%) responded reliably to chemosensory stimulation. Patients with olfactory loss exhibited pronounced olfactory and trigeminal adaptation within the long-term design, without such effects in healthy controls. Odor sensitivity correlated with both olfactory and trigeminal amplitude changes: the worse the olfactory sensitivity, the more pronounced chemosensory adaptation. Conclusions: The results help to explain the patients’ complaints in terms of the fast adaptation towards chemosensory stimuli, for example during eating and drinking. The differences in adaptation in patients with olfactory loss and healthy controls could serve as a clinical criterion to gauge olfactory dysfunction.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37506378 Variations of olfactory function with circadian timing and chronotype 456 469 EN Y. Mai Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Germany M.C. Rosbach Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Germany T. Hummel Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Germany 3100 10.4193/Rhin23.150 Background: Cumulative animal studies have suggested that olfaction can be regulated by circadian clock. However, human studies on the topic are relatively limited. The present study thus aimed to investigate diurnal variation in olfaction in healthy adults while examining potential modulating factors. Methods: We conducted four rounds of testing on 56 healthy adults (32 women) aged 31 ± 12 years, throughout a single day, during morning (8:00-10:00 h), noon (12:00-14:00 h), afternoon (16:00-18:00 h), and evening (20:00-22:00 h). At the first appointment, participants completed full olfactory function testing using the Sniffin’ Sticks, questionnaires on medical history, nasal symptoms, sleep quality, and chronotype, and were assessed for blood pressure, heart rate, peak nasal inspiratory flow (PNIF), attention level, and rated their smell ability, nasal patency, wakefulness, and concentration level using visual analog scale (VAS) ratings. Subsequent appointments measured olfactory threshold, attentional level, PNIF, blood pressure, heart rate and VAS ratings repeatedly. Results: Olfactory threshold (OT) scores varied significantly between different times of the day, with the highest score in the evening and the lowest in the morning. Similar differences were also observed in PNIF, with the highest value in the evening and the lowest in the morning. However, there were no significant correlations between OT score and PNIF across all four-time testing, as well as between differences in [OT evening â€" OT morning] and [PNIF evening â€" PNIF morning]. Furthermore, a generalized linear mixed model indicated that the testing time of the morning, evening chronotype, self-reported body mass index (BMI), rated smell ability, and rated nasal patency significantly predicted the Sniffin' Sticks OT score. Conclusions: Olfactory function fluctuates throughout the waking hours of the day, with the highest olfactory sensitivity observed in the evening and the lowest in the morning. This pattern is also seen in nasal patency. However, it appears that the circadian changes of nasal airflow may not significantly depend on the circadian changes of the olfactory sensitivity. In addition, chronotype and BMI may regulate such olfactory-circadian variation. These findings provide important insights for future research on the accurate diagnosis and treatment of olfactory dysfunction.

International Rhinologic Society Rhinology 0300-0729 61 5 2023 10 1 37454274 Investigation of the efficacy of systemic N-Acetyl Cysteine therapy preventing nasal mucositis following radiotherapy 470 480 EN N.K. Çelebi Ear Nose Throat Department, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey S.K. Ã-ztürk Ear Nose Throat Department, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey Ä° PalaoÄŸlu Ear Nose Throat Department, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey A. Somay Ear Nose Throat Department, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey G. Yaprak Radiation Oncology Department, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul, Turkey E. Algül Radiation Oncology Department, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul, Turkey H.S. Deveci Ear Nose Throat Department, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey 3096 10.4193/Rhin22.487 Background: Radiotherapy (RT) is one of the main methods used in the treatment of head and neck cancers but may cause mucosal side effects in the tumor area and surrounding structures. These include nasal mucosal disorders and chronic rhinosinusitis due to disruption of the mucociliary system. This situation seriously affects the quality of life of the patients and there is no accepted effective method for its treatment yet. In our study, we aimed to examine the side effects of RT on the nasal mucosa and mucociliary system and to investigate histopathologically and immunohistochemically the effectiveness of N-acetyl cysteine (NAC) in preventing these side effects of RT. Methodology: The study was carried out with 30 female Sprague Dawley rats devided in three groups. No intervention was made in the control group. On the second day of the experiment, 30 Gy radiotherapy was applied to the head area in the RT group. NAC was administered intraperitoneally at a dose of 1 g/kg/day for 14 days from the first day of the study to the RT+ NAC group. On the second day, 30 Gy of radiotherapy was applied to the head area 1 hour after the NAC application. On the 14th day, 1 hour after NAC was applied to the RT+NAC group, all animals were sacrificed. The nasal mucosa samples were stained with hematoxylin-eosin, and the intensity and extent of staining sentan in the nasopharyngeal tissue samples were evaluated by immunohistochemical staining using anti-SNTN antibody. Results: The loss of cilia in the nasal tissue was lower in the RT+NAC group than in the RT group. The intensity and extent of staining in the nasopharyngeal tissue of Sentan was higher in the RT+NAC group than in the RT group. Mucosal neutrophil and mononuclear inflammatory cell infiltration in the nasal tissue, vascular dilatation, hyperemia and hemorrhage, erosion and shedding of the mucosal epithelium, mucosal ulceration were found to be similar in the RT+NAC group and the control group. It was milder in the RT+NAC group than in the RT group, but not statistically significant. Conclusions: Radiotherapy caused pathological changes in the nasal mucosa, caused loss of cilia and a decrease in the level of Sentan, the cilia apical protein. The results of our study showed that NAC treatment can reduce the side effects of RT on the nasal mucosa. It also showed that NAC was effective in preventing the loss of cilia, which is the building block of the mucociliary system, and improving the expression of Sentan.