Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

To proceed or not to proceed: ENT surgery in paediatric patients with acute upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection is the most common non-preventable cause of surgery cancellation. Consequently, surgeons and anaesthesiologists involved in elective ENT surgical procedures frequently face a dilemma of whether to proceed or to postpone surgery in affected children. METHODS: A literature review was conducted and a practical assessment algorithm proposed. CONCLUSION: The risk-benefit assessment should take into consideration the impact of postponing the surgery intended to bring relief to the child and the risks of proceeding with general anaesthesia in an inflamed airway. The suggested algorithm for assessment may be a useful tool to support the decision of whether to proceed or to postpone surgery.

H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report.

Low frequency repetitive TMS (rTMS) of a cortical seizure focus is emerging as an antiepileptic treatment. While conventional rTMS stimulators activate only superficial cortical areas, reaching deep epileptic foci, for example in temporal lobe epilepsy (TLE), is possible using specially designed H-coils. We report the results of rTMS in a young adult with pharmacoresistant bilateral TLE who underwent three courses (of 10, 15, and 30 daily sessions) of unilateral rTMS over the hemisphere from which seizures originated most often. Seizure frequency was assessed before and after each block of rTMS sessions, as was the tolerability of the procedure. Seizure frequency declined significantly, by 50 to 70% following each rTMS course. All sessions were well-tolerated.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Severity of pneumococcal versus non-pneumococcal acute otitis media in children.

BACKGROUND: Pneumococcal acute otitis media (AOM) has been previously considered as a more severe disease than that caused by other otopathogens, based on clinical and/or otologic scores. We sought to test this hypothesis in the pneumococcal conjugated vaccine (PCV) era. METHODS: Children <6 years who presented with 'severe' AOM episodes with middle ear fluid (MEF) cultures during 2008-2013 were retrospectively identified. 'Severe' AOM episodes were considered if tympanocentesis was required or if spontaneous otorrhea was present. Data were extracted for demographics, clinical and laboratory tests. Children were categorised according to their PCV status as 'unimmunised' or 'PCV7/PCV13 immunised' and according to their MEF culture results into the 'pneumococcal' or the 'non-pneumococcal' group. Leukocytosis was defined as white blood cells (WBC) count >15 000/µL, and elevated C-reactive protein (CRP) level was considered as >50 mg/L. RESULTS: Of 295 eligible AOM episodes, 106 (36%) were culture positive. Children in the pneumococcal group (65, 61%) had a significantly higher WBC counts and higher CRP levels, were more often <2 years old and were more prone to complicate with acute mastoiditis (AM), compared to children in the non-pneumococcal group, P = 0.03, P = 0.02, P = 0.04 and P = 0.03, respectively. In the pneumococcal group, unimmunised children had higher WBC counts when compared with PCV13-immunised children (P = 0.04), but there were no appreciable differences in CRP levels between unimmunised and PCV7/PCV13-immunised children. CONCLUSION: Pneumococcal AOM is associated with higher leukocytosis and CRP levels than non-pneumococcal AOM. Circulating Streptococcus pneumoniae strains causing 'severe' AOM in PCV13-immunised children yielded lower inflammatory responses when compared with unimmunised children.

Forty-one recent cases of invasive zygomycosis from a global clinical registry.

BACKGROUND: Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited. PATIENTS AND METHODS: Fungiscope-A Global Rare Fungal Infection Registry is an international university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. RESULTS: Forty-one patients with invasive zygomycosis from central Europe and Asia were registered. The most common underlying conditions were malignancies (n = 26; 63.4%), diabetes mellitus (n = 7; 17.1%) and solid organ transplantation (n = 4; 9.8%). Diagnosis was made by culture in 28 patients (68.3%) and by histology in 26 patients (63.4%). The main sites of infection were the lungs (n = 24; 58.5%), soft tissues (n = 8; 19.5%), rhino-sinu-orbital region (n = 8; 19.5%) and brain (n = 6; 14.6%). Disseminated infection of more than one non-contiguous site was seen in six patients (14.6%). Mycocladus corymbifer was the most frequently identified species (n = 10, 24.4%). A favourable response was observed in 23 patients (56.1%). Overall survival was 51.2% (n = 21). At diagnosis, four patients (9.8%) were on continuous antifungal prophylaxis with itraconazole (n = 1; 2.4%) or posaconazole (n = 3; 7.3%). Initial targeted treatment with activity against zygomycetes was administered to 34 patients (82.9%). Liposomal amphotericin B was associated with improved response (P = 0.012) and survival rates (P = 0.004). CONCLUSIONS: Pathogen distribution and, consequently, drug susceptibility seem to vary across different geographic regions. Furthermore, protection from invasive zygomycosis for patients on posaconazole prophylaxis is not absolute. Our findings indicate that the use of liposomal amphotericin B as first-line treatment for patients diagnosed with zygomycoses merits further investigation, preferably in the form of a clinical trial.

Laryngeal cancer in acquired immunodeficiency syndrome.

With improved survival, more AIDS patients, especially heavy smokers and alcohol abusers, may be confronted with laryngeal squamous cell carcinoma. Since curative treatment may require aggressive combined therapy, these patients, often suffering from immunosupression and poor general condition, present unique therapeutic challenges. The objective of the study was to describe treatment dilemmas. This case report presents a detailed description of an AIDS patient with carcinoma of the larynx. A patient with T3N0M0 laryngeal carcinoma and AIDS underwent tracheotomy and biopsy, followed by severe neck and pulmonary infection. After convalescence, radiotherapy was administered, with no evidence of a disease during a 3.5-year follow-up. During his remaining life, the patient developed severe psychoaffective disorder, his immune state deteriorated until he demised from sepsis. In conclusion, patients with HIV infection, especially having a history of tobacco or alcohol abuse, should be carefully examined for head and neck carcinoma that is likely to be more aggressive. Following surgery, AIDS patients may have worse wound healing and a greater tendency to contract infections. Radiotherapy and especially chemotherapy may cause life-threatening complications. Although early detection may increase survival, curative treatment should involve many disciplines and extra caution.

High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation.

Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the field's magnitude by as much as 25% while also decreasing the field's decay with depth along specific directions. The focality, as measured by the area where the field's norm is greater than 1/sq.rt.2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coil's inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.

Magnetic acupressure for management of postoperative nausea and vomiting: a preliminary study.

BACKGROUND: To assess the efficacy of magnetic acupressure in the prevention of postoperative nausea and vomiting (PONV). METHODS: Fifty-eight patients were included in this randomized, double blind, preliminary prospective study. Thirty-three underwent ear, nose, and throat (ENT) procedures and twenty-five underwent gynaecological procedures. A magnet patch (M) or a placebo patch (P) was applied to patients in each group randomly. The patch was applied 15 min before surgery to P6 a point situated above the wrist, on the medial aspect of the arm between the palmaris longus and flexor carpi radicis (REF point). Anaesthesia was standardized for all patients. Primary study endpoints included PONV scores and number of rescue antiemetic administrations. Secondary endpoints included pain scores, percentage of patients who required rescue analgesics and satisfaction scores. Study variables were measured on arrival in the PACU and 8, 16 and 24 h after surgery. RESULTS: The global incidence of PONV was 50%. We found no significant difference in the incidence of PONV between ENT patients (46%) and gynaecology patients (56%), and no difference between patients who received magnet treatment (47%) and those that did not (54%). Patients receiving the magnet had a similar satisfaction level (75% satisfied) to those receiving placebo (73% satisfied). In addition, magnet-treated patients had similar pain and PONV scores, and a similar percentage of patients in each groups received postoperative rescue analgesics. Finally, there was no difference in the number of rescue antiemetic administrations between the two groups. CONCLUSION: The use of magnetic acupressure as a prophylactic antiemetic treatment prior to ENT or gynaecology surgeries produced no benefit when compared to placebo.

High-permeability core coils for transcranial magnetic stimulation of deep brain regions.

Stimulation of deep brain regions with Transcranial Magnetic Stimulation (TMS) may have an important role as a therapy to treat chemical dependency and depression. The coils traditionally used in TMS, however, have a poor performance in stimulating deep neurons. In this work we study the usage of high permeability cores combined with coils specifically designed to induce fields that decay slowly with depth. By using the finite elements method we show that the use of such cores increases the field's magnitude, decreases its decay rate and improves its focality. Such improvements make these high permeability core coils more suited to stimulate deep brain regions.

[Eating and swallowing disorders in children].

INTRODUCTION: Eating and swallowing disorders in children are common and reflected in several symptoms, yet they are not well known. PATIENTS: Three patients are presented to demonstrate the spectrum of the problems, the diagnosis and the multidisciplinary team approach to treatment. DISCUSSION: To enable safe eating and thriving, swallowing and eating disorders need to be recognized and treated, according to the child's development. This can be done by a multidisciplinary team, such as the one at The Edith Wolfson Medical Center.

Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging.

Convection-enhanced drug delivery (CEDD) is a novel approach to enhance the delivery of drugs directly into brain tumors. We have used diffusion-weighted MRI (DWMRI) to monitor the effects of intratumoral CEDD in three brain tumor patients treated with Taxol. Clear changes in the images and the water diffusion parameters were observed shortly after the initiation of treatment. Initially, a bright area corresponding to decreased diffusion appeared, followed by the appearance of a dark area of increased diffusion within the bright area. The time to appearance of the dark area varied among the patients, suggesting different response rates. In this work, we have demonstrated the feasibility of using DWMRI as a noninvasive tool to achieve unique early tissue characterization not attainable by other conventional imaging methods.

High urine 1-hydroxypyrene glucuronide concentrations in Linxian, China, an area of high risk for squamous oesophageal cancer.

Most squamous cell carcinomas of the oesophagus in low-risk populations are attributable to alcohol and tobacco consumption, but the aetiologic agents in many high-risk populations have yet to be definitively identified. Linxian, China has some of the highest oesophageal cancer rates in the world. Recent studies suggest that an association exists between high-level exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), and the development of oesophageal cancer. The inhabitants of this high-risk region extensively use coal and wood for cooking and heating in unvented stoves, and thus may be exposed to PAHs produced during the incomplete combustion of these fuel sources. High levels of B[a]P were recently detected in staple food samples from Linxian and histopathologic changes that may be associated with PAH exposure have also been identified in oesophagectomy specimens from the region. In an effort to determine whether this high-risk population is exposed to high levels of PAHs, voided urines from non-smokers (n = 22) without occupational exposure were collected and analysed using immunoaffinity chromatography and synchronous fluorescence spectroscopy for 1-hydroxypyrene glucuronide, a PAH metabolite and index biomarker for mixed PAH exposure. The median urine 1-hydroxypyrene glucuronide concentration (2.06 pmol ml(-1)) was equivalent to concentrations detected in current smokers. To the authors' knowledge, this represents the first report of elevated urine 1-hydroxpyrene glucuronide concentrations in Linxian, and the first biologic confirmation that the inhabitants of this rural, non-industrial, high oesophageal cancer risk region are exposed to carcinogenic PAHs.

Noninvasive real-time monitoring of intracellular cancer cell metabolism and response to lonidamine treatment using diffusion weighted proton magnetic resonance spectroscopy.

We have used diffusion-weighted proton magnetic resonance spectroscopy (DWMRS) to noninvasively selectively observe only the intracellular metabolites of breast cancer and melanoma cell lines in vitro in real time. Breast cancer cell lines representing different stages in breast cancer progression were chosen for study. Intracellular biochemical profiles of six cell lines perfused in alginate beads were obtained. Spectral differences between groups of cell lines, including choline, lactate, and threonine peaks, were investigated. We also monitored response to the antineoplastic agent, lonidamine (LND), as a function of time and drug concentration in perfused cancer cells. Previous studies reported that this drug induced intracellular acidification and lactate accumulation. Diffusion weighted proton spectra demonstrated a 2- to 9-fold increase in the intracellular lactate signal as a response to LND treatment in several cancer cell lines. These results are consistent with the hypothesis that the principal mechanism of LND in some cancer cells is marked inhibition of lactate transport. Moreover, we have shown that there is a factor of two to three between the response of melanoma cells and that of some types of breast cancer cells. The higher sensitivity of the melanoma cells, as predicted by proton DWMRS, was correlated with changes in water-suppressed magnetic resonance spectra and confirmed by a biological assay. This study demonstrates the feasibility of using DWMRS for monitoring intracellular metabolism and for studying the effects and mechanisms of action of anticancer drugs. We believe that this method can be used for noninvasive clinical applications, such as the differentiation between benign and malignant tissue, real-time monitoring of response to therapy, dose response, and toxicity effects.

Nasal nitric oxide does not control basal nasal patency or acute congestion following allergen challenge in allergic rhinitis.

Nasal nitric oxide (NO), a powerful vasodilator, could control the filling of nasal capacitance vessels, thus determining nasal patency and mediating the acute congestion accompanying allergen challenge. We examined the effect of topical N-nitro-L-arginine-methyl-ester (L-NAME; 100 to 200 mg), an NO synthase inhibitor, on nasal NO and on nasal patency assessed by acoustic rhinometry in 7 subjects with nasal allergy, and in 4 subjects we examined the effects of nasal allergen challenge on nasal NO before and after a short course of nasal steroid. After L-NAME, nasal NO fell to 42.1%+/-15.7% of baseline (p < .0001) with no significant change in minimal cross-sectional area. After allergen challenge, acute congestion was associated with a significant fall in nasal NO, which returned to baseline by 4 hours, when the congestion resolved. Repeat challenge after 2 weeks of nasal corticosteroid yielded similar findings. A role for NO in modulating vascular tone was not supported by the present study.

An objective analysis of the impact of lateral rhinotomy and medial maxillectomy on nasal airway function.

OBJECTIVE: The lateral rhinotomy and medial maxillectomy procedure, while known to interrupt nasal valve supports, has not previously been reported to adversely affect nasal airway function. The purpose of this study was to utilize state-of-the-art techniques to objectively analyze the impact of this procedure on nasal airway function. DESIGN: The study design was retrospective and subject controlled. METHODS: The study population was derived from an academic, tertiary-referral, otolaryngology-head and neck surgery department with an estimated catchment population of 4 million people. Subjects included 21 consecutive, long-term postoperative patients who had undergone lateral rhinotomy and medial maxillectomy for inverted papilloma. Objective measures included vestibular cephalometric measurements, airflow rhinomanometry, and acoustic rhinometry. RESULTS: Statistically significant results reveal that although lateral rhinotomy and medial maxillectomy are associated with alar collapse, both overall nasal airflow and valve areas are increased. CONCLUSION: Lateral rhinotomy and medial maxillectomy does not adversely affect nasal airway function. This appears to be the result of concomitant resection of the functionally dominant inferior turbinate. This suggests that lateral rhinotomy performed in conjunction with operations not requiring inferior turbinectomy, such as anterior craniofacial resection, may adversely affect nasal airway function.