An olfactory self-test effectively screens for COVID-19.

Background: Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online. Methods: Each participant was instructed to select 5 household items, and rate their perceived odor pleasantness and intensity using an online visual analogue scale. We used this data to assign an olfactory perceptual fingerprint, a value that reflects the perceived difference between odorants. We tested the performance of this real-time tool in a total of 13,484 participants (462 COVID-19 positive) from 134 countries who provided 178,820 perceptual ratings of 60 different household odorants. Results: We observe that olfactory ratings are indicative of COVID-19 status in a country, significantly correlating with national infection rates over time. More importantly, we observe indicative power at the individual level (79% sensitivity and 87% specificity). Critically, this olfactory screen remains effective in participants with COVID-19 but without symptoms, and in participants with symptoms but without COVID-19. Conclusions: The current odorant-based olfactory screen adds a component to online symptom-checkers, to potentially provide an added first line of defense that can help fight disease progression at the population level. The data derived from this tool may allow better understanding of the link between COVID-19 and olfaction.

Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature.

BACKGROUND: Regional differences in the underlying causes, manifestations and treatment of mucormycosis have been noted in studies covering Europe, Asia and South America. OBJECTIVES: To review cases of mucormycosis across the Middle East and North Africa (MENA) region in order to identify epidemiological, treatment and outcome trends in this region. PATIENTS/METHODS: Cases of proven or probable invasive mucormycosis from the region were identified from the FungiScope® database and the medical literature. For each case, information on underlying condition, site of infection, pathogenic species, therapeutic intervention, type of antifungal therapy and outcome were analysed. RESULTS: We identified 310 cases of mucormycosis in the MENA region. The number of reported cases increased by decade from 23 before 1990 to 127 in the 2010s. In this region, the most common underlying conditions associated with mucormycosis were diabetes mellitus (49.7%) and conditions associated with immunosuppression (46.5%). The majority of patients received treatment with antifungals (93.5%), with a large proportion treated with both antifungals and surgery (70.6%). Overall mortality rates decreased from 47.8% before 1990 to 32.3% in the 2010s. CONCLUSIONS: The number of reported cases of mucormycosis in the MENA region has risen over the past few decades, in line with increases in the number of patients with underlying conditions associated with this infection. Although the majority of patients received treatment with antifungal therapies and/or surgery, the associated mortality rate remains high and there is a clear need for more effective prevention and treatment strategies in the MENA region.

Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population.

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r=-0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before wide-spread testing can be facilitated.

Diabetes in the practice of otolaryngology.

Diabetes mellitus is the most common endocrine disease, characterized by chronic hyperglycemia. The hyperglycemic milieu leads to endothelial injury in blood vessels of variant size, which results in microangiopathy and macroangiopathy (atherosclerosis). Consequential ischemia of nerves and hyperglycemia by itself lead to nerve degeneration and generalized neuropathy, affecting most often the sensory peripheral nerves and the autonomic nervous system. Auditory, vestibular and olfactory sensorium may be compromised by DM. People with DM have an increased susceptibility to infection, as a result of neutrophil dysfunction and impaired humoral immunity. Therefore DM predisposes to certain infectious diseases, such as fungal sinusitis or malignant otitis externa, which are rare in general population. Recovery from infections or from injuries may be compromised by coexisting DM. In this review we discuss complications of DM in the head and neck region. Otolaryngologists and general practitioners should be alert to specific conditions related to DM and be minded of the relevant complications and consequences.

Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current diagnosis and management practices.

BACKGROUND: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel have not been described. AIMS: to assess prevalence utilizing state-of-the-art diagnostic techniques, and describe clinical features, diagnostic and management practices in Israel. METHODS: A national multicenter study from 2012 to 2013 recruited patients diagnosed or suspected of having PCD. Diagnosis was verified using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA); Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining (IF) for ciliary proteins, and genetic analysis. RESULTS: Of the 203 patients recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and 1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and 21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%), rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied widely between centers with TEM assessed in 55% and abnormal in 61% of these. Management included antibiotics and airway clearance. Diagnostic verification revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic TEM, 58% diagnostic IF and, 57% genetic diagnosis. CONCLUSIONS: PCD in Israel is rare, with comprehensive diagnostic tests showing prevalence in children similar to Europe. Prevalence was higher in non-Jews, associated with parental consanguinity. Diagnostic and management practices vary. Referral centers providing comprehensive diagnostic and care capabilities should be established.

Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities.

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures.

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose.

Orbital complications associated with paranasal sinus infections - A 10-year experience in Israel.

OBJECTIVE: Orbital involvement is the most common complication of sinus infections. The epidemiology of the disease is continuously changing in the antibiotic era. MATERIALS AND METHODS: Data on patients who were hospitalized due to acute sinusitis and orbital complications were retrospectively collected and analyzed from four medical centers in Israel during the years 2002-2012. RESULTS: 288 patients were included in the study, the average age was 14.4 years, 180 were males, and 220 were children. No significant annual increase in the number of patients was noted. The lowest number of patients was found during the summer 19.4%. A linear direct correlation was found between older age and prolonged hospital stay. Children were presented with a significantly higher Chandler score than adults. No patient had cavernous sinus thrombosis. 101 (35%) patients received antibiotics before hospital admission. Their average hospital stay was similar to those who were not treated prior to admission. 106 patients (39.8%) had fever. A direct correlation was found between older age and the presence of fever. 102 (35.4%) patients had leukocytosis. The difference in white blood cell count between patients younger than two years of age to the other groups was statistically significant. Forty four (15.3%) patients underwent surgical intervention. A direct correlation was found between leukocytosis and older age to surgery. CONCLUSIONS: Periorbital cellulitis occurs mainly in children and males and is less frequent in the summer. Children tend to have worse orbital involvement with lower temperatures than adults. Older age and leukocytosis are associated with surgical intervention.

A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis.

We investigated the cause of situs inversus totalis (SIT) in two siblings from a consanguineous family. Genotyping and whole-exome analysis revealed a homozygous change in NME7, resulting in deletion of an exon causing an in-frame deletion of 34 amino acids located in the second NDK domain of the protein and segregated with the defective lateralization in the family. NME7 is an important developmental gene, and NME7 protein is a component of the γ-tubulin ring complex. This mutation is predicted to affect the interaction of NME7 protein with this complex as it deletes the amino acids crucial for the binding. SIT associated with homozygous deletion in our patients is in line with Nme7(-/-) mutant mice phenotypes consisting of congenital hydrocephalus and SIT, indicating a novel human laterality patterning role for NME7. Further cases are required to elaborate the full human phenotype associated with NME7 mutations.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

Acute Mastoiditis in Children: Necessity and Timing of Imaging.

BACKGROUND: Acute mastoiditis (AM) can be clinically diagnosed, with an option for supplemental imaging: computed tomography (CT) scan and magnetic resonance imaging (MRI). Debate widely exists whether clinical diagnosis alone is sufficient, in view of the risk of missing undetected complications. We sought to study the reasons leading to the performance of an imaging study during AM course. METHODS: Medical records of children younger than 8 years who were admitted from 2005 to 2014 with AM were retrospectively reviewed. Data included medical history, signs and symptoms, laboratory results, imaging studies, treatment methods and final outcomes. RESULTS: Eighty-six children were diagnosed with 88 AM episodes. Of the AM episodes, 55 (63%) were in boys and 46 (52%) were in children younger than 2 years. All children were treated with parenteral antibiotics, and 82 (95%) underwent myringotomy on admission. Only 20 (23%) children underwent imaging studies, on the 6th median day. Of those, 20 (100%) children underwent CT scans, and 3 (15%) underwent additional MRI studies. The reasons for imaging studies included suspected subperiosteal abscess (9 of 20, 45%), lack of improvement despite adequate medical therapy (7, 35%) and focal neurological signs (4, 20%). Sixteen (16%) children underwent surgery for these pathologies: subperiosteal abscesses (n = 12,), jugular vein thrombosis (n = 2), perisinus empyema (n = 2), epidural abscess (n = 2) and Luc abscess (n = 1). CONCLUSIONS: Most children presenting with AM can be diagnosed clinically and do well with intravenous antibiotics and myringotomy. CT and MRI imaging should be reserved for children with suspected AM-related intracranial complications.

Endoscopic Occlusion of Tracheoesophageal Fistula in Ventilated Patients Using an Amplatzer Septal Occluder.

Acquired tracheoesophageal fistula (TEF) is a challenging, life threatening condition. It most commonly appears in critically ill patients requiring prolonged mechanical ventilation, who cannot withstand open neck or chest surgery. An endoscopic technique could be better tolerated by these patients. We present our experience using a cardiac Amplatzer ASD septal occluder for an endoscopic TEF repair in ventilation-dependent patients. Two high risk patients underwent the procedure under general anesthesia and close respiratory monitoring. In one patient the device was inserted through the trachea and in the other through the esophagus. In both cases fistula closure was achieved for different periods of time allowing the patients a temporary relief of symptoms. The procedure was well tolerated by the patients, and no significant adverse effect documented. The technique was successful as a temporary solution for unstable patients with TEFs and should be considered as a treatment modality for similar patients.

A reach-out system for video microscopy analysis of ciliary motions aiding PCD diagnosis.

BACKGROUNDS: High-speed Video-Microscopy Analysis (HVMA) is now being used to aid diagnosis of Primary Ciliary Dyskinesia (PCD). Only a few centers however, are equipped with the available resources and equipment to perform these tests. We describe our experience in HVMA reaching-out to many more peripheral and relatively remote areas. A portable computer with HVMA software, video camera and a microscope were used. Fourteen disperse pediatric centers were reached and a total of 203 subjects were tested within a relatively short time (Clinical Trial Registration: NCT 01070914 (registered February 6, 2010). RESULTS: With an average time of 20 minutes per patient, the system enabled us to test approximately 10-15 subjects per day. A valid HVMA result was made in 148 subjects and helped in the diagnosis of PCD in many of the patients who were subsequently confirmed to have PCD by electron microscopy and/or immunofluoresence and/or genetics and/or nasal Nitric Oxide testing. The sensitivity of abnormal HVMA to accurately predict PCD was 90.2%. DISCUSSION AND CONCLUSION: This is the first report of an out-reach system to record HVMA for improved diagnosis of PCD in remote regions that are not within reach of PCD centers and experts. It provides immediate preliminary results and instantaneous feedback to the physician, patient and his/her family members in these areas. Future studies to compare this system to conventional desk top systems are warranted. TRIAL REGISTRATION: NCT 01070914 (registered February 6, 2010).

Changing trends of acute otitis media bacteriology in central Israel in the pneumococcal conjugate vaccines era.

BACKGROUND: The widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has changed acute otitis media (AOM) bacteriology. Only scattered data with regard to this effect of PCV13 have been published so far. METHODS: We retrospectively identified children <6 years of age who presented to our hospital with AOM, and had middle ear fluid (MEF) cultures obtained during tympanocentesis or from spontaneous otorrhea during 2008-2013, when PCV7 (2009) and PCV13 (2010) were gradually introduced in the Israeli National Immunization Program. Data were extracted for demographics, clinical and microbiologic parameters, according to vaccination status. RESULTS: Of the 295 eligible AOM episodes reported in 279 children, 224 (76%) had MEF cultures from tympanocentesis and 71 (24%) from spontaneous otorrhea. Boys and children <2 years of age contributed 178 (60%) and 219 (74%) AOM episodes, respectively. Acute mastoiditis complicated 58 (20%) of these episodes. None of the children were PCV immunized in 2008, but >90% had received ≥1 PCV dose(s) by 2011 or later. Of the 106 (36%) MEF cultures which tested positive for otopathogens, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and multiple bacteria grew in 60 (57%), 39 (37%), 2 (2%) and 5 (5%) episodes, respectively. S. pneumonia-positive MEF culture rate in unimmunized children (31, 69%) was significantly higher than in PCV7-immunized children (22, 59%) or PCV13-immunized children (12, 50%), P = 0.04 and P = 0.02, respectively. CONCLUSION: PCV7 and PCV13 implementations in the Israeli National Immunization Program were associated with a rapid reduction of "severe" pneumococcal AOM episodes.

Treatment of horizontal canal BPPV: pathophysiology, available maneuvers, and recommended treatment.

OBJECTIVES/HYPOTHESIS: To describe the pathophysiology of horizontal canal benign paroxysmal positional vertigo, the available maneuvers for its management, and the recommended treatment. DATA SOURCES: PubMed, Cochrane library. REVIEW METHODS: Review of the available literature. RESULTS: Two theories of pathophysiology underlying the disease are described, along with available maneuvers reflecting those theories; and videos of the maneuvers are provided. A comparison of available treatments is made. CONCLUSION: A variety of maneuvers is available related to the pathophysiology underlying the disease. The treatment chosen should be appropriate to the patients' ages, general conditions, and other diseases they may have. No treatment was found to be superior over the others regarding the success rate. In the case of geotropic nystagmus, the Gufoni maneuver is superior in its ease of performance. When it comes to apogeotropic nystagmus, the Barbecue and Gufoni maneuvers have comparable success rates.

A Russian adaptation of the tinnitus handicap inventory.

OBJECTIVE: To establish a Russian version of the English THI. DESIGN: The English THI (THI-E) was translated into Russian by two bilingual investigators, independently. The final Russian THI version (THI-R) was constructed by a third investigator, from the two translations. This version was administered to fifty consecutive patients at a tinnitus clinic. Participants also assessed the loudness of their tinnitus, and completed the Russian versions of the Beck's depression inventory and the state anxiety Inventory. STUDY SAMPLE: The participants were fifty consecutive patients (older than 18 years of age with a tinnitus lasting over three months) who were treated at a tinnitus clinic. RESULTS: A very good internal consistency was found (α = 0.94), with significant correlation between the THI-R score and the Beck depression inventory score. Factor analysis confirmed a uni-dimensional structure of the inventory. CONCLUSIONS: A valid and reliable THI-R questionnaire was constructed.

Deep neck infections in cervical injection drug users.

OBJECTIVES/HYPOTHESIS: To characterize deep neck infections (DNI) in adult intravenous drug users (IDUs) who injected illicit substances to their neck, in comparison to DNI in non-IDUs. STUDY DESIGN: Retrospective, cohort study. METHODS: Data were retrieved from medical charts of adult DNI patients in a secondary hospital during 2000-2013. Clinical, radiologic, and microbial data were extracted and tabulated following categorization into 2 patient groups: IDUs and non-IDUs. RESULTS: Of the 136 patients identified with DNI, 20 (15%) were IDUs; of them 80% were males. IDUs were significantly younger than non-IDUs (mean age, 35 ± 10 vs. 44 ± 16 years, P = .01). All IDUs had multiple comorbidities. IDUs presented for medical examination and hospitalization later in the course of their disease, and the most common involved neck spaces were consistent with areas where cervical injections are commonly performed. Abscess formation was more common in IDUs than non-IDUs (16 [80%] vs. 79 [68%], respectively, P = .04). Despite later presentation of IDUs and their higher rate of comorbidities, laboratory data, microbiology cultures, and disease course were similar to non-IDUs. CONCLUSIONS: Although IDU and non-IDU differ in DNI presentation, both groups had good outcomes. DNI in IDUs frequently evolved into abscesses, and most were found in the anterior triangle deep to sternocleidomastoid (SCM), posterior triangle, and anterior triangle superficial to SCM, in concordance with the injection sites. LEVEL OF EVIDENCE: 4.

Adult supraglottitis: changing trends.

There is no clinical dynamic staging system which scores according to severity all the anatomical regions in adult supraglottitis. The objective of the study was to describe the demographics, clinical presentation, interventions and outcomes of adult patients diagnosed with acute supraglottitis (AS), and to study the correlation of a new AS classification with the need for airway intervention, in comparison with the current classification. This was a retrospective, cohort study conducted at a secondary medical care center. Adults diagnosed with AS from the years 1990-2013 were identified. Data were extracted for demographic and clinical information and there was no intervention. The main outcome and measures were the need for airway intervention. 288 eligible patients were enrolled. AS incidence rate was 4.3/100,000 patients/year. The mean age was 50 ± 16 years. Sore throat (94 %) and dysphagia (88 %) were the most common presenting symptoms. Patients were hospitalized either in the Otolaryngology Department (n = 255, 89 %) or in the Intensive Care Unit (n = 33, 11 %). Of the latter, 19 (58 %) had an airway securing intervention procedure. Our suggested classification was more sensitive than the current one for predicting the need for intubation (p = 0.03). Signs and symptoms of AS in adults are different from those in children. Adult patients presenting with oropharyngeal complaints should be suspected for AS and treated appropriately.

Cardiovascular risk factors as causes for hearing impairment.

The purpose of this paper is to provide a contemporary review of the correlation between cardiovascular risk factors (CVRFs) and hearing impairment (HI) . We conducted a comprehensive review of the literature in order to assess the effects of the different CVRFs on HI. We focused on the pathological findings in the inner ear and their correlation with cochlear function in population-based studies. We found that CVRFs adversely affect hearing acuity. HI diagnosis should be accompanied by detecting and treating CVRFs, according to the presented outline, which may augment hearing rehabilitation and improve the general health and the well-being of the patient. © 2014 S. Karger AG, Basel.

Acute mastoiditis in the pneumococcal conjugate vaccine era.

Following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive for Streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.