International clinical assessment of smell: An international, cross-sectional survey of current practice in the assessment of olfaction.

OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.

Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination.

BACKGROUND: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping. SUMMARY: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text. KEY MESSAGES: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field.

Tissue expression analysis of cervical mucus proteome.

Cervical mucus is a viscous fluid functioning as a cervix plug. Products of the endometrial and cervical glands can be detected in the cervical mucus. Cervical mucus is further enriched with transudate originating from the fallopian tubes and proteins originating from the ovaries, peritoneum and distant tissues. With increasing levels of ovarian estrogens, the properties of cervical mucus for possible collection and processing change appropriately. For these reasons, we chose a group of 10 patients treated in the center of assisted reproduction by controlled ovarian stimulation for in vitro fertilization. This study focuses on the proteomic characterization of cervical mucus and localizes the possible sources of the identified proteins. The most abundant proteins were extracellular proteins, mainly mucins; however, most of the identified proteins, present usually in lower quantities, were of intracellular origin. The tissue analysis revealed that proteins from female reproductive organs are also expressed in other tissues in addition to female reproductive organs, but also proteins specific to the testis, liver, placenta, retina, and cerebellum. This study confirms the suitability and high potential of cervical mucus as a source of proteomic bio-markers not only for the dia-gnosis of the female reproductive tract.

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.

Outcome of Continuous Positive Airway Pressure Adherence Based on Nasal Endoscopy and the Measurement of Nasal Patency-A Prospective Study.

The gold standard for treating obstructive sleep apnea in adults is continuous positive airway pressure (CPAP). However, it can be difficult to convince patients to adhere to this therapy. The aim of this study was to determine the relationship between nasal endoscopy findings/nose patency and CPAP adherence. Material and methods: A cohort of 450 consecutive patients suspected of having OSA were prospectively enrolled. For further analyses, 47 OSA patients undergoing CPAP treatment were selected (13 females and 34 males, average age, 65.3 years, BMI 34.1, apnea-hypopnea index. AHI 51.0). The patients were divided into two groups: patients with good CPAP adherence (n = 35) and patients who did not adhere to CPAP therapy (n = 12). The influence of nasal endoscopy and flow measurement on CPAP adherence was explored. Results: We found a statistical independence between adherence to CPAP and AHI (p = 0.124), T90 (p = 0.502), endoscopic findings (p = 0.588) and nasal patency measured by a flowmeter (p = 0.498). Conclusions: In our studied sample, endoscopic findings and nasal patency measured by a flowmeter were not predictors of CPAP non-adherence in the first year of the treatment. Our data show that while an endoscopic finding in the nasal cavity could indicate that a patient has a severe obstruction, compliance with CPAP therapy is not reduced in these patients and neither is it reduced with a decrease in nasal flow, according to our observation.

Selected pathological conditions affecting endometrial receptivity.

OBJECTIVE: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. METHODS: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on "endometrial receptivity", "polycystic ovary syndrome", "endometriosis", "SARS-CoV-2". RESULTS: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbio-me. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium bio-psy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbio-me or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. CONCLUSION: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

Assisted reproduction in patients with Klinefelter syndrome.

OBJECTIVE: The goal of this article is to present the current knowledge of Klinefelter syndrome and its impact on male reproductive function as well as the current treatment options. METHODS: PubMed/Medline, WoS and Scopus were searched for articles indexed until November 2021. TEXT: Klinefelter syndrome is a chromosomal aberration with an additional X chromosome in males. This may adversely affect testicular growth and spermatogenesis, thus resulting in male infertility. Recently, new knowledge has appeared about the treatment of male infertility. CONCLUSION: Interdisciplinary approach enables early dia-gnosis and treatment of patients with Klinefelter syndrome. Assisted reproductive technology is essential for infertility treatment in patients with Klinefelter syndrome.

Olfactory Outcomes With Dupilumab in Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Loss of smell (LoS) is one of the most troublesome and difficult-to-treat symptoms of severe chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: To assess the impact of dupilumab on sense of smell in severe CRSwNP. METHODS: In the randomized SINUS-24 and SINUS-52 studies, adults with severe CRSwNP received dupilumab 300 mg subcutaneously or matching placebo every 2 weeks for 24 or 52 weeks, respectively. Smell was assessed using daily patient-reported LoS score (0-3) and University of Pennsylvania Smell Identification Test (UPSIT; 0-40). Data from the 2 studies were pooled through week 24. Relationships between patient phenotypes and smell outcomes were also assessed. RESULTS: We randomized 724 patients (286 placebo, 438 dupilumab); mean CRSwNP duration was 11 years; 63% had prior sinonasal surgery. Mean baseline LoS was 2.74. Dupilumab produced rapid improvement in LoS, evident by day 3, which improved progressively throughout the study periods (least squares mean difference vs placebo -0.07 [95% CI -0.12 to -0.02]; nominal P < .05 at day 3, and -1.04 [-1.17 to -0.91]; P < .0001 at week 24). Dupilumab improved mean UPSIT by 10.54 (least squares mean difference vs placebo 10.57 [9.40-11.74]; P < .0001) at week 24 from baseline (score 13.90). Improvements were unaffected by CRSwNP duration, prior sinonasal surgery, or comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Baseline olfaction scores correlated with all measured local and systemic type 2 inflammatory markers except serum total immunoglobulin E. CONCLUSIONS: Dupilumab produced rapid and sustained improvement in sense of smell, alleviating a cardinal symptom of severe CRSwNP.

Adenomyosis - its possible effect on endometrial function and receptivity

OBJECTIVE: There have been many studies on adenomyosis, which can impair the quality of life of a woman. There are various kinds of opinions on the pathogenesis, diagnostics and treatment of adenomyosis. The goal of this article is to present the current knowledge of adenomyosis and its impact on the endometrial function and receptivity. METHODS: PubMed/Medline, Web of Sciences and Scopus were searched for the articles in English indexed until February 2021 with terms of: adenomyosis, endometrial receptivity, and infertility. RESULTS: Recent studies on angiogenesis and epithelial-mesenchymal transition in the endometrium bring new information on the ethiology and pathogenesis of adenomyosis. In clinical practice, the main diagnostic methods of adenomyosis include transvaginal ultrasound, magnetic resonance imaging or hysteroscopy, although the definitive confirmation is set by histopathological examination. The rules of #Enzian classification of endometriosis should be applied for the classification of adenomyosis. The treatment of adenomyosis should consider individual clinical presentation and reproductive plans of a patient and should be performed in centers for the treatment of endometriosis. CONCLUSION: Adenomyosis affects endometrial vascularisation and epithelial-mesenchymal transition/mesenchymal-epithelial transition; thus, it can be the cause of irregular uterine bleeding or embryo implantation failure. The research and analysis of endometrial proteome could lead to the new ways of adenomyosis treatment.

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.

Effectiveness of Neonatal Hearing Screening System: A 12-Year Single Centre Study in the Czech Republic.

PURPOSE: The study aims to evaluate the number of examined newborns and the results of screening for twelve years (2008-2019) and to assess the effectiveness of the established system of neonatal hearing screening. DESIGN AND METHODS: The study was designed as a retrospective longitudinal data analysis. The data included all the children (19,043) born in the hospital and also children (74) transferred from other healthcare facilities. A total of 19,117 children were included in the research group. RESULTS: In the first three years, a higher number of children did not pass the hearing screening, which was followed by a declining trend in the following years. After the first year of screening (2008), there was an improvement in diagnosis linked with a decrease in false-positive screening results (from 9.4% to 6.4%; p = 0.002). From 2008 to 2015, the ratio of children with positive screening to those with negative screening had a steady or declining trend. CONCLUSIONS: The results showed a reduction in false-positive results after the first year of the screening program, probably due to improved care management and a gradual increase in the skills of the nurses performing the screening. PRACTICE IMPLICATIONS: The cornerstones of neonatal hearing screening are a sufficient number of trained neonatology nurses, their mutual substitutability and the availability of a hearing screening device in the newborn ward every day. The results imply the importance of periodic evaluation of the obtained data, enabling early detection of possible deficiencies in the hearing screening system.

The influence of a child's age on the evaluation of smells and their hedonistic assessment.

Olfactory function in children is most commonly evaluated using the odour identification test despite the fact that it is difficult to properly name odorants for young children. The goal of this study was to evaluate the pleasantness rating of odorants by children. The participants were 182 healthy children: the first group included 63 girls and 59 boys (aged 6-7) and the second included 31 girls and 29 boys (aged 11-12). We assessed olfaction using (1) standard method of odorant identification using a U-Sniff test and (2) classifying the hedonic tone of the odorants into 5 categories. The identification test's median differed in younger and older groups of children; the median was 8 and 10 respectively (p < 0.01). The unpleasant hedonic tones were butter, fish and onion. The pleasant hedonic tones were apple, orange and peach. The younger usually categorised hedonic tones as pleasant, compared with the older children, who categorised the odorant's hedonic tones more often as neutral (p < 0.01).Conclusion: This study demonstrated that older children are able to identify odours better than younger ones. The categorisation of hedonic tones differed depending on the subject's age. The younger children tended to categorise odorants as being pleasant and older children as neutral. What is Known: • The test of odour identification is the most popular because it is reliable, practical, rapid and commercially available. • The ability to identify odours improves with age in children. What is New: • The categorisation of hedonic tones differs depending on age. The older children categorise odorants as being neutral significantly more often than younger children do.

Hearing screenings for preschool children: A comparison between whispered voice and pure tone audiogram tests.

INTRODUCTION: This prospective study compares the efficiency of two hearing screening tests performed on preschool children. These tests are known as whispered voice test and pure tone audiometry. METHODS: Standard hearing screenings were performed on five-year old children using a whispered voice test followed by ENT examination with pure tone audiometry. RESULTS: A total of 827 children were included in the study. Hearing loss (>25 dB) was observed in 5.8% of the evaluated children (n = 48), being bilateral in only 1.6% (n = 13) of these cases. Slight hearing impairment (hearing loss of 16-25 dB) was observed in 25.4% (n = 210) of the children, with 14.5% bilateral cases (n = 120). Interestingly, 62 children (7.5%) were under suspicion of hearing loss by their parents; however, an audiogram revealed the poor consistency of this diagnosis (sensitivity 20.8%, Cohen's kappa coefficient of 0.048). The whispered voice test (6 m distance) throwed a hearing impairment diagnosis in 807 (48.8%) of examined ears; however, its sensitivity was of only 56.5%, with a specificity of 51.6% and Cohen's kappa coefficient of 0.0254 (poor). CONCLUSION: The hearing loss incidence in preschool children coupled with the low efficacy of whispered voice tests and the parents' unreliability during the hearing impairment survey advocate for a more efficient audiometric hearing screening before beginning school attendance.

Giant locally advanced and metastatic squamous cell skin carcinoma of head and neck region: case report.

INTRODUCTION: At the present time, the skin tumors are among the most common cancers. Optimal therapy is based on the extent of the disease and the age of the patient. The need for radiotherapy occurs for inoperable locally advanced tumors and in the event of failure, salvage surgery is applied. MATERIALS AND METHODS: We provided a case report of an older patient with giant squamous cell skin carcinoma and a review of published articles. RESULTS: We present a rare case of giant squamous cell skin carcinoma with metastatic satellite tumors that was primarily treated with curative radiotherapy. Five months after radiotherapy, a recurrent tumor was detected at the site of origin and the treatment was completed by salvage surgery. Full remission was achieved for four years. CONCLUSION: Despite the seemingly incurable finding it is always necessary to consider radical treatment regardless of the patient´s age. Curative treatment could achieve long term remission in the group of older patients.

Development of an International Odor Identification Test for Children: The Universal Sniff Test.

OBJECTIVE: To assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test. STUDY DESIGN: This is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). RESULTS: Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean ± SD of 9.88 ± 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r27 = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%. CONCLUSIONS: The U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.

Pleasantness of olfactory and trigeminal stimulants in different Italian regions.

Although individuals categorize odors according to their pleasantness, experience may also influence odor perception-a phenomenon that partially explains why different populations perceive odors differently. Italy, which comprises 20 regions, is characterized by very different cultures. In the present study, we investigated for the first time how Italian regional differences can affect odor perception. 254 healthy volunteers coming from northern, central, southern Italy, and Sicily, one of the two major Italian islands, were recruited in Padua, Rome, Naples, and Syracuse, respectively. Olfactory function was tested with Sniffin' Sticks identification subtest. Subjects who had a score in the range within the mean identification value ± 1 SD, in accordance with the age classes identified in the literature, were asked to judge the odor pleasantness of 20 substances. The hedonic tone of the odorants was categorized as pleasant, neutral, unpleasant, and very unpleasant. Some odorants were appreciated more in northern Italy than in the other parts of the country, whereas others were appreciated more in the south and in Sicily than in the north. Unpleasant odorants were judged less unpleasant in central Italy. Some odorants such as strawberry and vanilla were perceived similarly in all the regional areas. Our study indicates that in Italy, hedonic perception of odorants differs probably in relation with genetic, cultural, and environmental factors. Further investigation is needed to delve deeper into the factors that influence the quality odor perception amongst humans.

[Olfactory function in patients undergoing FESS for chronic rhinosinusitis]. / Cich u pacientu podstupujících endonazální endoskopickou chirurgii.

Patients with chronic rhinosinusitis (CRS) often suffer from loss of olfactory function. Rhinosinusitis can be treated either by medical therapy or surgically (FESS). Postoperative outcome in terms of improving sense of smell has been controversial so far. The aim of our study was to determine the patients who would have better postoperative outcomes in terms of improving olfactory function. We collected data of patients undergoing FESS for chronic rhinosinusitis (either with or without nasal polyps) at our department during the years 2012-2015. These patients had their olfactory function examined with Odorized markers test (OMT) up to 24 hours before surgery. After that we chose the best result in OMT found out in visits from 4 weeks to 4 months after surgery. We were comparing individual risk factors out of the patients´ anamnesis, CT scan and physical examination. 51 patients were enrolled in this study. 25 % of patients showed improvement of their olfactory function, no change was recorded in 55 % of patients and 20 % of patients showed deterioration of olfaction. Before surgery we found out statistically significant difference in results of OMT between the patients with and without nasal polyps and with and without asthma (p = 0,0016, resp. p = 0,04). After surgery the difference was no longer statistically significant (p = 0,17, resp. p = 0,12). Correlation with age and Lund-Mackay score showed changes after surgery. No statistically significant difference in results of OMT was found out before and after surgery in other observed risk factors (oral corticosteroids before surgery, smoking, revision surgery and middle turbinate resection). Changes in olfactory function in patients with chronic rhinosinusitis after surgery are hard to predict. Our results show that nasal polyps, asthma, lower age and higher Lund-Mackay score are factors which predict better postoperative outcome.

New test of odor pleasantness in Parkinson's disease.

The New Test of Odor Pleasantness (NTOP) evaluates the hedonicity of olfactory stimulants. The aim of this study was to compare results of the NTOP, the Sniffin' Sticks test, and the Odorized Marker Test (OMT) in patients with Parkinson's disease (PD). The study sample comprised 30 PD patients (mean age 71±7.36 years) and the control group made up of 31 non-PD subjects (mean age 68±12.39 years). Sociodemographic data, medical history and tests of cognitive function were investigated. Olfaction was evaluated using the NTOP, Sniffin' Sticks test and OMT. The PD patients, compared with the control group, recorded significantly lower scores on all three tests: NTOP (p=0.00), Sniffin' Sticks (p=0.02), OMT (p=0.00). The NTOP was the test preferred by 55% of the subjects. This preference was more marked in the PD group. This study shows that the NTOP is a valuable method within the complex array of olfactory screening tools used in PD.

Retronasal testing of olfactory function: an investigation and comparison in seven countries.

Flavor perception is to a large extent determined by olfaction, and persons who lost their sense of smell consequently complain about strongly reduced enjoyment of food. The retronasal olfactory function is especially important for flavor appreciation. The aim of this study was to compare retronasal function across different cultures and to develop a test that is applicable across cultures. Identification of 39 retronasal applied odor probes was tested in a total of 518 participants of seven countries; 292 of them were healthy, and 226 exhibited a smell disorder. A retest was performed with 224 of the healthy participants. Furthermore, all participants were tested for orthonasal threshold, identification, and discrimination ability. Significant cultural differences in identification ability were found in 92% of the probes. The 20 probes that could be identified above chance in healthy participants of all countries and that could differentiate between patients and controls were selected for the final retronasal test. This test was well able to differentiate between controls and patients in different countries and showed a good coherence with the orthonasal test (r = 0.80) and a good retest-reliability (r = 0.76). Furthermore, it is age-independent. The strong cultural differences observed in retronasal identification underline the necessity to develop a culturally independent instrument. This retronasal test is easy to apply and can be used across different countries for diagnostics and clinical research.