Otolaryngology adverse events following COVID-19 vaccines.

OBJECTIVE: Since the outbreak of COVID-19 pandemic, the international scientific community aimed at developing a vaccine to protect against the infection and prevent serious forms of the disease. To date, various adverse events of COVID-19 vaccines have been reported, mostly mild to moderate. MATERIALS AND METHODS: In this short communication, we reviewed available literature and described the most frequent otolaryngology adverse events reported after COVID-19 vaccination. RESULTS: The most frequent adverse events following COVID-19 vaccine described in the literature are represented by audiovestibular symptoms, such as tinnitus, sudden sensorineural hearing loss, vertigo, and dizziness. Other side effects include facial nerve palsy, epistaxis, and oral manifestations (lichen planus, bleeding, ulcers, and vesicles). CONCLUSIONS: COVID-19 vaccine is of utmost importance in limiting the spread of SARS-CoV-2. Otolaryngology-related side effects have been described, but none was severe or life threatening. The mechanisms underlying these effects are still mostly unknown.

Drugs inducing hearing loss, tinnitus, dizziness and vertigo: an updated guide.

OBJECTIVE: The awareness of audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo, has widely increased in the recent years. The present guide represents an update of the previous documents published by the authors in 2005 and 2011 on drug-induced ototoxicity and vestibulotoxicity. MATERIALS AND METHODS: The authors performed a comprehensive analysis of audio-vestibular side effects of commercially available drugs based on the British National Formulary, a pharmaceutical reference book that contains a wide range of useful information and advice on prescription and pharmacology. RESULTS: Commercially available drugs and their active principles have been classified based on their audio-vestibular side effects, as reported by the pharmaceutical companies and/or health agencies. Drugs have been categorized based on the field of application, the therapeutic indication and the pharmacological properties. CONCLUSIONS: General practitioners, otolaryngology, neurology and audiology specialists should be aware of possible audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo. The present guide represents a practical tool to rapidly identify potential audio-vestibular side effects of drugs as reported by the pharmaceutical companies and/or health agencies.

Dietary Restriction for The Treatment of Meniere's Disease.

Meniere's disease (MD) is an idiopathic inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss (SNHL), aural fullness and tinnitus. Endolymphatic hydrops (EH) of the inner ear is currently considered the pathophysiological mechanisms that underlies typical symptoms of MD. MD diagnosis is based on the criteria of the Baràny Society. There are many therapeutic options for MD, but none is considered effective by the scientific community. The first-line treatment commonly includes dietary modification, as low salt diet and reduction of alcohol and caffeine daily intake. Although some studies showed a positive effect of these dietary restrictions, even in the prevention of recurrences, currently there is no uniform consensus on their usefulness. New dietary approach, such SPC-flakes, are being evaluated: further assessments will be needed to validate their use in clinical practice.

Correlation between otitis media with effusion and cranial deformation in children.

OBJECTIVE: Otitis media with effusion (OME), defined as the presence of fluid in the ear without signs of an acute infection, usually occurs after acute otitis media and could result in reduced sound transmission with hearing loss. Several risk factors have been suggested to be associated with OME, as well as the relationships between morphology anomalies of cranial bones and ear infections. The aim of this study is to investigate the correlation between OME and cranial deformation in a pediatric population. PATIENTS AND METHODS: Eighteen children (13 males and 5 females) with a diagnosis of unilateral OME based on otolaryngologic examination, conductive hearing loss and an asymmetric tympanogram type were enrolled in the study. Patients underwent osteopathic and physical examinations to evaluate the presence of cranial deformations. RESULTS: Our study showed a high percentage of skull asymmetry (94%) in the study sample; children were mainly dolichocephalic and with atypical swallowing (72%). Particularly, we observed an occipital flattening, mainly ipsilateral to the ear affected by OME. CONCLUSIONS: The results of the present study indicated that a high percentage of children with OME present a skull asymmetry with concomitant dolichocephaly, known to be associated with high arched palate which is also related to a higher incidence of OME.

Ultraviolet photochemistry of 2-bromothiophene explored using universal ionization detection and multi-mass velocity-map imaging with a PImMS2 sensor.

The ultraviolet photochemistry of 2-bromothiophene (C4H3SBr) has been studied across the wavelength range 265-245 nm using a velocity-map imaging (VMI) apparatus recently modified for multi-mass imaging and vacuum ultraviolet (VUV, 118.2 nm) universal ionization. At all wavelengths, molecular products arising from the loss of atomic bromine were found to exhibit recoil velocities and anisotropies consistent with those reported elsewhere for the Br fragment [J. Chem. Phys. 142, 224303 (2015)]. Comparison between the momentum distributions of the Br and C4H3S fragments suggests that bromine is formed primarily in its ground (2P3/2) spin-orbit state. These distributions match well at high momentum, but relatively fewer slow moving molecular fragments were detected. This is explained by the observation of a second substantial ionic product, C3H3+. Analysis of ion images recorded simultaneously for several ion masses and the results of high-level ab initio calculations suggest that this fragment ion arises from dissociative ionization (by the VUV probe laser) of the most internally excited C4H3S fragments. This study provides an excellent benchmark for the recently modified VMI instrumentation and offers a powerful demonstration of the emerging field of multi-mass VMI using event-triggered, high frame-rate sensors, and universal ionization.

Acquired sensorineural hearing loss in children: current research and therapeutic perspectives.

The knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debated.

When alarm bells ring: emergency tinnitus.

OBJECTIVE: The aim of this study is to develop a diagnostic-therapeutic algorithm for those suffering from tinnitus who seek emergency aid. MATERIALS AND METHODS: A literature review has been performed on articles from the last 30 years. RESULTS: It is important to activate medical or surgical diagnostic and therapeutic strategies, in order to safeguard and rehabilitate the various functions affected. Psychiatric comorbidity is the most frequent pathological condition of those with serious or catastrophic tinnitus. In these cases, mortality risk is linked to suicide, morbidity to tinnitus-correlated distress. CONCLUSIONS: Tinnitus, mainly linked to loss of hearing, is a frequent symptom among the population at large. About 7% of those affected by tinnitus turn to their doctor to solve their problem, while between 0.5 and 2% request urgent medical assistance. Their cry for help may be the result of an acute onset of tinnitus or the rapid impairment of an already chronic condition. Tinnitus is not considered an urgent ear, nose and throat (ENT) condition by the Associazione Otorinolaringologi Ospedalieri Italiani (AOOI) [Italian Association of Hospital ENT], even though there are many pathological conditions, sometimes serious, associated with tinnitus and emergency action is necessary to reduce the risk of morbidity and mortality.

Cancer stem cells in laryngeal cancer: what we know.

Cancer stem cells (CSCs) are a group of cells with eternal life or infinite self-renewal ability, which have high migrating, infiltrative, and metastatic abilities. Though CSCs only account for a small proportion in tumors, the high resistance to traditional therapy exempts them from therapy killing and thus they can reconstruct tumors. Previous studies found that heterogeneity of cancer cells extensively exists in head and neck cancers. Our current knowledge, about CSCs in the laryngeal cancer (LC), largely depends on head and neck studies. Given the lack of systematic data about CSCs in LC, we propose a review of the literature, reporting the evidences of CSCs in tumorigenesis of LC, with the purpose to provide new insights into the prevention and/or treatment of laryngeal carcinoma.

Modifications to a commercially available linear mass spectrometer for mass-resolved microscopy with the pixel imaging mass spectrometry (PImMS) camera.

RATIONALE: Imaging mass spectrometry is a powerful analytical technique capable of accessing a large volume of spatially resolved, chemical data from two-dimensional samples. Probing the entire surface of a sample simultaneously requires a detector with high spatial and temporal resolutions, and the ability to observe events relating to different mass-to-charge ratios. METHODS: A commercially available time-of-flight mass spectrometer, designed for matrix-assisted laser desorption/ionization (MALDI) analysis, was combined with the novel pixel imaging mass spectrometry (PImMS) camera in order to perform multi-mass, microscope-mode imaging experiments. A number of minor modifications were made to the spectrometer hardware and ion optics so that spatial imaging was achieved for a number of small molecules. RESULTS: It was shown that a peak width of Δm50 % < 1 m/z unit across the range 200 ≤ m/z ≤ 800 can be obtained while also achieving an optimum spatial resolution of 25 µm. It was further shown that these data were obtained simultaneously for all analytes present without the need to scan the experimental parameters. CONCLUSIONS: This work demonstrates the capability of multi-mass, microscope-mode imaging to reduce the acquisition time of spatially distributed analytes such as multi-arrays or biological tissue sections. It also shows that such an instrument can be commissioned by effecting relatively minor modifications to a conventional commercial machine.

Deafness in Italy: an epidemiological and socio-demographic study.

OBJECTIVES: Hearing loss is very common in our society, but epidemiological data on deafness in Italy is lacking. A.I.R.S. onlus (Italian Association for Research on Deafness) yearly launches the National Day for the Fight Against Deafness (NDFAD). During this events, that are held every year, it is possible to perform a free hearing test in all the facilities that have joined the initiative throughout Italy (240 hospitals joined in 2011). AIM: to report data collected throughout the "A.I.R.S. National Day for the Fight against Deafness" of the last years, focusing in particular but not only on audiometric outcomes. METHODS: demographic and social data, as well as audiometric outcomes, was collected on forms that have been subsequently stored in a on-line database and analyzed with MySQL and Microsoft Excel. CONCLUSIONS: This data are important in order to describe the "hearing health" of the Italian population, and is a first step towards creating a database with epidemiological and preventive aims, a strongly felt need both at national and at regional level.

Recurrent respiratory papillomatosis by HPV: review of the literature and update on the use of cidofovir.

Recurrent respiratory papillomatosis is a viral induced disease characterised by exophytic epithelial lesions affecting the larynx. The problem with its treatment is the high recurrence of papilloma growth after surgical removal. The aim of our review is to analyse the actual use of cidofovir, an agent used in adjuvant therapy. We have reviewed 6 manuscripts that included a total of 118 patients. The parameters taken into account were: concentration of infiltrated cidofovir (mg/ml), therapeutic response, relapse-free time (months), side effects, genotypes (HPV-6/11/18) and evolution of dysplasia. Cidofovir was injected at concentrations from 2.5 to 15 mg/ml, therapeutic response was from 56.25% to 82.3% and relapse-free time was from 10.05 to 49 months. There were 2 cases of dysplasia during therapy. Ten patients had been infected by HPV-6, 4 patients by HPV-11 and 10 patients by HPV-6 and HPV-11. The purposes of our review include the following: to stress that the juvenile form is more aggressive than other forms, to demonstrate than the drug has good adjuvant action although it does not significantly change the final response to the disease, to show that side effects are modest and, finally, to disprove the hypothesis that cidofovir may promote evolution towards dysplasia. In conclusion, combination of surgical removal and injection of cidofovir is associated with good response in recurrent respiratory papillomatosis.

Vogt-Koyanagi-Harada syndrome.

OBJECTIVES: The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed. RESULTS AND CONCLUSION: Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.

Cogan's syndrome: an autoimmune inner ear disease.

OBJECTIVES: The objective of our study was to review our current knowledge of the aetiopathogenesis of Cogan's syndrome, including viral infection and autoimmunity, and to discuss disease pathogenesis with relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiopathogenesis and pharmacotherapy of Cogan's syndrome from 1945 to 2012 were analysed. RESULTS AND CONCLUSIONS: Cogan's syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA). Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogan's syndrome.

The application of the fast, multi-hit, pixel imaging mass spectrometry sensor to spatial imaging mass spectrometry.

Imaging mass spectrometry is a powerful technique that allows chemical information to be correlated to a spatial coordinate on a sample. By using stigmatic ion microscopy, in conjunction with fast cameras, multiple ion masses can be imaged within a single experimental cycle. This means that fewer laser shots and acquisition cycles are required to obtain a full data set, and samples suffer less degradation as overall collection time is reduced. We present the first spatial imaging mass spectrometry results obtained with a new time-stamping detector, named the pixel imaging mass spectrometry (PImMS) sensor. The sensor is capable of storing multiple time stamps in each pixel for each time-of-flight cycle, which gives it multi-mass imaging capabilities within each pixel. A standard velocity-map ion imaging apparatus was modified to allow for microscope mode spatial imaging of a large sample area (approximately 5 × 5 mm(2)). A variety of samples were imaged using PImMS and a conventional camera to determine the specifications and possible applications of the spectrometer and the PImMS camera.

Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide.

The present work on drug-induced ototoxicity, tinnitus and vertigo represents the update and revision of a previous guide to adverse drug reactions for italian physicians (2005). The panorama of drug-induced side effects causing ototoxicity or symptoms such as tinnitus or dizziness and vertigo has enlarged in recent years, thanks to a better knowledge and a more specific attention of pharmaceutical firms and drug-control institutions. In daily clinical practice, there is a need for the family physician and the ENT specialist or audiologist (also in consideration of the possible medico-legal implications) to focus the attention on the possible risk of otological side effects. This would allow a clinical risk-benefit evaluation, weighing the possible clinical advantage in their field of competence against possible otological side-effects. The list of active ingredients and drugs is subdivided in categories based on their audiological and otoneurological side-effects, that have been signaled by the drug companies and/or ministerial notes. Drugs have also been subcategorized with regards to the field in which they are applied, the therapeutic indications and the clinical behaviour. They have also been organized in alphabetical order, for an easier consultation. The guide above, even if initially conceived for being used in Italy, also presents a more general and international interest, expecially as for as the concepts of pharmacology and the features of the active ingredients are concerned. The guide is, therefore, useful as for as we are concerned to any physician, regardless of the country he/she operates in.

Characterization study of an intensified complementary metal-oxide-semiconductor active pixel sensor.

An intensified CMOS active pixel sensor (APS) has been constructed for operation in low-light-level applications: a high-gain, fast-light decay image intensifier has been coupled via a fiber optic stud to a prototype "VANILLA" APS, developed by the UK based MI3 consortium. The sensor is capable of high frame rates and sparse readout. This paper presents a study of the performance parameters of the intensified VANILLA APS system over a range of image intensifier gain levels when uniformly illuminated with 520 nm green light. Mean-variance analysis shows the APS saturating around 3050 Digital Units (DU), with the maximum variance increasing with increasing image intensifier gain. The system's quantum efficiency varies in an exponential manner from 260 at an intensifier gain of 7.45 × 10(3) to 1.6 at a gain of 3.93 × 10(1). The usable dynamic range of the system is 60 dB for intensifier gains below 1.8 × 10(3), dropping to around 40 dB at high gains. The conclusion is that the system shows suitability for the desired application.

Dynamic position and force measurement for multiple optically trapped particles using a high-speed active pixel sensor.

A high frame rate active pixel sensor designed to track the position of up to six optically trapped objects simultaneously within the field of view of a microscope is described. The sensor comprises 520 x 520 pixels from which a flexible arrangement of six independent regions of interest is accessed at a rate of up to 20 kHz, providing the capability to measure motion in multiple micron scale objects to nanometer accuracy. The combined control of both the sensor and optical traps is performed using unique, dedicated electronics (a field programmable gate array). The ability of the sensor to measure the dynamic position and the forces between six optically trapped spheres, down to femtonewton level, is demonstrated paving the way for application in the physical and life sciences.

Enhanced imaging in low dose electron microscopy using electron counting.

We compare the direct electron imaging performance at 120keV of a monolithic active pixel sensor (MAPS) operated in a conventional integrating mode with the performance obtained when operated in a single event counting mode. For the combination of sensor and incident electron energy used here, we propose a heuristic approach with which to process the single event images in which each event is renormalised to have an integrated weight of unity. Using this approach we find enhancements in the Nyquist frequency modulation transfer function (MTF) and detective quantum efficiency (DQE) over the corresponding integrating mode values by factors of 8 and 3, respectively.

Experimental observation of the improvement in MTF from backthinning a CMOS direct electron detector.

The advantages of backthinning monolithic active pixel sensors (MAPS) based on complementary metal oxide semiconductor (CMOS) direct electron detectors for electron microscopy have been discussed previously; they include better spatial resolution (modulation transfer function or MTF) and efficiency at all spatial frequencies (detective quantum efficiency or DQE). It was suggested that a 'thin' CMOS detector would have the most outstanding properties [1-3] because of a reduction in the proportion of backscattered electrons. In this paper we show, theoretically (using Monte Carlo simulations of electron trajectories) and experimentally that this is indeed the case. The modulation transfer functions of prototype backthinned CMOS direct electron detectors have been measured at 300keV. At zero spatial frequency, in non-backthinned 700-mum-thick detectors, the backscattered component makes up over 40% of the total signal but, by backthinning to 100, 50 or 35mum, this can be reduced to 25%, 15% and 10%, respectively. For the 35mum backthinned detector, this reduction in backscatter increases the MTF by 40% for spatial frequencies between 0.1 and 1.0 Nyquist. As discussed in the main text, reducing backscattering in backthinned detectors should also improve DQE.