Human Nasal Turbinate Tissues in Organ Culture as a Model for Human Cytomegalovirus Infection at the Mucosal Entry Site.

The initial events of viral infection at the primary mucosal entry site following horizontal person-to-person transmission have remained ill defined. Our limited understanding is further underscored by the absence of animal models in the case of human-restricted viruses, such as human cytomegalovirus (HCMV), a leading cause of congenital infection and a major pathogen in immunocompromised individuals. Here, we established a novel ex vivo model of HCMV infection in native human nasal turbinate tissues. Nasal turbinate tissue viability and physiological functionality were preserved for at least 7 days in culture. We found that nasal mucosal tissues were susceptible to HCMV infection, with predominant infection of ciliated respiratory epithelial cells. A limited viral spread was demonstrated, involving mainly stromal and vascular endothelial cells within the tissue. Importantly, functional antiviral and proleukocyte chemotactic signaling pathways were significantly upregulated in the nasal mucosa in response to infection. Conversely, HCMV downregulated the expression of nasal epithelial cell-related genes. We further revealed tissue-specific innate immune response patterns to HCMV, comparing infected human nasal mucosal and placental tissues, representing the viral entry and the maternal-to-fetal transmission sites, respectively. Taken together, our studies provide insights into the earliest stages of HCMV infection. Studies in this model could help evaluate new interventions against the horizontal transmission of HCMV.IMPORTANCE HCMV is a ubiquitous human pathogen causing neurodevelopmental disabilities in congenitally infected children and severe disease in immunocompromised patients. The earliest stages of HCMV infection in the human host have remained elusive in the absence of a model for the viral entry site. Here, we describe the establishment and use of a novel nasal turbinate organ culture to study the initial steps of viral infection and the consequent innate immune responses within the natural complexity and the full cellular repertoire of human nasal mucosal tissues. This model can be applied to examine new antiviral interventions against the horizontal transmission of HCMV and potentially that of other viruses.

A Novel Tool for Nasal Polyp Investigation: An Ex vivo Organ Culture System.

BACKGROUND: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited. OBJECTIVES: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function. METHODS: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250-500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids. RESULTS: Polyp tissue viability was retained for 2-3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production. CONCLUSIONS: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

The association between video-nystagmography and sensory organization test of computerized dynamic posturography in patients with vestibular symptoms.

OBJECTIVE: Vertigo is a complex symptom which imposes diagnostic and treatment challenges. Laboratory evaluation of vertigo includes video-nystagmography (VNG) and computerized dynamic posturography (CDP) for the evaluation of different aspects of this complaint. There are vague indications for each test and potential disagreements between them. The aim of this study is to examine the association between the test results of the VNG and sensory organization test (SOT) of CDP in patients referred for both vestibular tests. METHODS: Retrospective data regarding 56 patients age 17-82 years were collected. Patients suffered vestibular complaints and were referred for VNG and CDP evaluation on the same day. The level of agreement between VNG (including caloric test) and the vestibular input of the SOT for each patient was calculated. RESULTS: Among the study group, 10 showed abnormal caloric test results, of which 3 (5.4%) had normal vestibular input in the SOT, and 7 (12.5%) had impaired input (p = 0.724). Spontaneous nystagmus was recorded in 13 patients by VNG, of which 2(3.6%) had normal vestibular input and 11(19.6%) had impaired vestibular input (p = 0.056). CONCLUSIONS: This study shows no statistically significant association between the VNG test and SOT test results. Our results emphasize the difference between the tested aspects in each laboratory test, and the need to define specific indications for each of them. There is a marginally significant association between impaired vestibular input and spontaneous nystagmus, demonstrating the non-localizing nature of this sign.

[HORIZONTAL CANAL - BENIGN PAROXYSMAL POSITIONAL VERTIGO (HC-BPPV) - CLINICAL DIAGNOSTIC PROCEDURES].

INTRODUCTION: Horizontal canal benign paroxysmal positional vertigo (HCBPPV) is one form of benign paroxysmal positional vertigo. HC-BPPV is characterized by intermittent recurrent episodes of vertigo following a change in head position relative to gravity. HC-BPPV prevalence ranges from 5%-33% of all dizziness cases seen in otolaryngology, neurology and family physician clinics. Various factors, such as ear and head injury, can cause HC-BPPV. Cardiovascular disease and iatrogenic reasons are also implicated. Despite the prevalence of the disease, there are various forms of diagnostic procedures, some of which are unfamiliar to the therapist and some are controversial. This review aims to present the full range of methods of diagnosis of HC-BPPV, presenting their advantages and disadvantages.

Contribution of Treatment with Ear Popper for Hearing in Children with Middle Ear Effusion.

OBJECTIVES: we aim to assess the contribution of the EarPopper device to hearing in children with middle ear effusion (MEE). METHODS: The study has three parts, including 1. tympanometry and audiometry before and six weeks after using the EarPopper to evaluate the treatment's effect over time compared to a control group; 2. tympanometry before and immediately after using the EarPopper to evaluate immediate changes in middle ear pressure (MEP); 3. length of effect 90 min after use to assess pressure fluctuations over time. RESULTS: Part 1 was a follow-up six weeks after using the device, and the patients in the study group that completed the study showed a significant improvement in hearing threshold. The average gain in hearing threshold ranged from 9.1 dB to 14 dB compared to the control group's max improvement of 1.1 dB. In addition, MEP was significantly improved in the study group, as most Type Bs improved to Type A and C. Part 2 was the tympanometry immediately after using EarPopper and showed the majority of Type Cs turned into Type As. The majority of Type Bs remained unchanged. Part 3 was a follow-up 90 min after use; Type Cs that had improved to Type A demonstrated a decrease in pressure and return to negative pressure. CONCLUSIONS: use of the EarPopper device for six weeks is associated with an improved hearing threshold and middle ear status.

Gentamicin Vestibulotoxicity: Further Insights From a Large Clinical Series.

OBJECTIVE: To review insights gained from a 21-year experience with gentamicin-induced vestibulotoxicity including differences in vestibulotoxicity between single daily dosing (SDD) and multiple daily dosing (MDD) regimens. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: Patients with gentamicin vestibulotoxicity referred to the Hertz Multidisciplinary Neurotology Clinic between January 1993 and September 2014. INTERVENTION: None. MAIN OUTCOME MEASURES: Spectrum of vestibular dysfunction measured using videonystagmography, vestibular evoked myogenic potentials, video head impulse testing, and magnetic scleral search coil testing. RESULTS: Of 53 patients with gentamicin-induced vestibulotoxicity, 24 received SDD and 29 received MDD treatment. The most common indications for treatment were sepsis, endocarditis, and osteomyelitis. Angular acceleration receptor function (semicircular canals) was more commonly affected than linear acceleration receptor function (otolithic organ of the saccule; 100% vs. 62%). A significant proportion of patients (53%) developed vestibulotoxicity in the absence of nephrotoxicity and 40% experienced vestibulotoxicity in a delayed fashion up to 10 days posttreatment cessation (mean 3.9 ±â€Š0.7). Therapeutic monitoring did not necessarily prevent delayed vestibulotoxicity. Nephrotoxicity was less common for SDD compared with MDD (60% vs. 35%, p = 0.01). However, the SDD group experienced vestibulotoxicity at a lower cumulative dose (6.3 vs. 7.0 g, p = 0.04) and shorter duration of therapy (20.7 vs 29.4 d, p = 0.02). CONCLUSIONS: Our study further highlights important insights regarding gentamicin-induced vestibulotoxicity. While SDD is associated with decreased risk for nephrotoxicity compared with MDD, it confers a higher risk for vestibulotoxicity.

Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule.

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) strains represent a major global health problem. Their virulence is mediated by the concerted activity of an array of virulence factors including toxins, a type III protein secretion system (TTSS), pili, and others. We previously showed that EPEC O127 forms a group 4 capsule (G4C), and in this report we show that EHEC O157 also produces a G4C, whose assembly is dependent on the etp, etk, and wzy genes. We further show that at early time points postinfection, these G4Cs appear to mask surface structures including intimin and the TTSS. This masking inhibited the attachment of EPEC and EHEC to tissue-cultured epithelial cells, diminished their capacity to induce the formation of actin pedestals, and attenuated TTSS-mediated protein translocation into host cells. Importantly, we found that Ler, a positive regulator of intimin and TTSS genes, represses the expression of the capsule-related genes, including etp and etk. Thus, the expression of TTSS and G4C is conversely regulated and capsule production is diminished upon TTSS expression. Indeed, at later time points postinfection, the diminishing capsule no longer interferes with the activities of intimin and the TTSS. Notably, by using the rabbit infant model, we found that the EHEC G4C is required for efficient colonization of the rabbit large intestine. Taken together, our results suggest that temporal expression of the capsule, which is coordinated with that of the TTSS, is required for optimal EHEC colonization of the host intestine.

Neurotological findings after electrical injury at the workplace.

OBJECTIVES/HYPOTHESIS: Neurotological findings secondary to electrical injuries have rarely been reported in the world literature. We attempt to characterize the neurotological findings following electrical injury and to determine the role head injury and loss of consciousness play in this population's clinical presentation. STUDY DESIGN: Retrospective cohort study. METHODS: A database containing 3,438 patients with work-related injuries was scanned for individuals who sustained and survived electrical injuries at work. Detailed analysis of the frequencies of presenting features and test results was performed. A comparative analysis was made between the subsets of patients with and without loss of consciousness and/or head injury. RESULTS: A cohort of 42 patients was identified. All patients had multiple symptoms. Dizziness was a significant complaint in all workers with electrical injuries. Other common complaints included tinnitus and imbalance. Characterization of these symptoms is provided in detail according to statistical frequency. In this cohort, 25 workers had a concomitant head injury and 17 workers had an associated loss of consciousness. There was no statistically significant difference when clinical presentation, examination, and balance testing results were compared between the subsets. CONCLUSIONS: Frequency and characterization of symptoms following electrical injury are provided. Dizziness is the most common presenting neurotological feature. Loss of consciousness and/or associated head injury do not affect the clinical presentation in this particular population. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:2126-2131, 2017.

The Association Between Vestibular Physical Examination, Vertigo Questionnaires, and the Electronystagmography in Patients With Vestibular Symptoms.

OBJECTS: Dizziness makes up a diagnostic and treatment challenge. The diagnostic accuracy of the medical history and vestibular physical examination in cases of vestibular symptoms is not clear. The aim of this study is to determine the association between vestibular physical examination, vestibular questionnaires, and electronystagmography (ENG) test in patients with vestibular symptoms. METHODS: This is a prospective study of 135 adults with vestibular symptoms. The subjects underwent targeted physical examination and filled vestibular questionnaires, including the Dizziness Handicap Inventory (DHI), before ENG testing. The results of the physical examination and questionnaires were compared with the final ENG findings. RESULTS: Of patients who had normal ENG results, 32.1% (17/52) showed abnormal physical examination, and 48.8% (40/82) of the patient who had normal physical examination showed abnormal ENG results ( P = .46). Among patients with severe disability by DHI, 46.4% (13/28) had an abnormal ENG, and 42.9% (12/28) had a normal ENG ( P = .39). CONCLUSIONS: This study did not demonstrate association between vestibular physical examination, vestibular questionnaires, and ENG results. Although history (augmented by questionnaires) and physical examination are the initial steps in the evaluation of vertigo, the current study suggests that they should be complemented by objective testing for evaluation of inner ear origin of vertigo.

Diagnosis and conservative management of late tracheotomy complications in chronic ventilator-dependent patients.

BACKGROUND: Complications associated with long-term tracheotomy are obstruction of the distal end of the tube by granulation tissue and tracheomalacia. These complications have traditionally been surgically treated. METHODS: Prospective study in a chronic ventilator-dependent division, including 234 consecutive patients with tracheotomy and mechanical ventilation. Endoscopic evaluation was performed in patients in whom there was respiratory distress with difficulty in passing a suction catheter through the tube, and/or increased inspiratory resistance and increased peak inspiratory pressure. RESULTS: Nineteen patients were diagnosed with granulation or tracheomalacia. Two patients were treated by surgical removal of the obstructing tissue. Nonsurgical patients were conservatively managed with symptoms' resolution by bypassing the pathology with a longer tube than the previous one or by an adjustable flange tube under endoscopic visualization, with a median symptom-free period of 433 days (range, 55-1230 days). CONCLUSION: In nonsurgical candidates, insertion of a longer tube is a conservative and feasible long-term treatment.

Ménière's Syndrome or Disease: Time Trends in Management and Quality of Evidence Over the Last Two Decades.

OBJECTIVE: To evaluate the evidence and trends in published literature on the treatment of Ménière's syndrome or disease (MS/D) by comparing studies published in the last two decades. DATA SOURCES: A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders groups trials register using a combination of MeSH. The date of last search was October 2014. STUDY SELECTION AND DATA EXTRACTION: Two hundred five studies (104 in decade I and 101 in decade II) were evaluated to report trends in the management of this condition, the differing levels of evidence published for each treatment modality, evaluate whether the guidelines published by the AAOHNS-Committee on Hearing and Equilibrium had been correctly employed, and whether the randomized controlled trials (RCTs) were compliant with the CONSORT guidelines. RESULTS: The number of published RCTs almost tripled from decade I (1994-2003) to decade II (2004-2103). There was a significant decline in the use of surgical intervention (p = 0.013); however, the number of studies involving the use of intratympanic injection remained largely unchanged. There was a shift in the level of evidence in published studies; studies with level 1 evidence tripled from decade I to II (4.8 to 17.8%, respectively) (p = 0.03); however, compliance with the AAOHNS-CHE criteria for reporting treatment outcomes and the CONSORT checklist was still poor. CONCLUSION: Although the evidence base on published literature on MS/D has improved over the last decade with an increase in emphasis on RCTs and quality of life (QoL) studies, a significant number of studies failed to follow AAOHNS-CHE criteria for reporting treatment outcome and the CONSORT criteria for reporting RCTs.

Cogan's syndrome--clinical guidelines and novel therapeutic approaches.

Cogan's syndrome (CS) is a rare chronic inflammatory disorder, classically characterized by interstitial keratitis and sensorineural hearing loss. Recurrent episodes of inner ear disease might result in deafness. In some patients, it may also be accompanied by systemic vasculitis. Diagnosis of CS is often missed or delayed due to its rarity, the nonspecific clinical signs at onset, and the lack of a confirmatory diagnostic test. The mechanisms responsible for CS are unknown; however, in the last decade, the pathogenesis has been somewhat elucidated, suggesting that the disease is a result of inner ear autoimmunity. The autoimmune hypothesis postulates the triggering of the disease by a viral infection via a number of mechanisms, which are mainly as follows: antigenic mimicry, self-perpetuating inflammation by cytokine release, and unveiling hidden epitopes. Aside from its clinical resemblance to other autoimmune disorders, some autoantigen has apparently been identified, namely, CD148 and connexine 26. Treatment should begin as early as possible. While treatment is based primarily on glucocorticoids, there is no standard alternative for patients who respond poorly. Failure of conventional treatment could lead to profound sensorineural hearing loss. From the limited data we have, infliximab seems to be the most promising biological remedy, enabling steroid tapering and leading to improvement in auditory/ocular disease, with better results when administered in early stages. Proposed guidelines for the use of infliximab in CS are found in the last table of the review, in an attempt to define the proper timing for initiating infliximab treatment in order to avoid permanent disability.

Extraction of a headscarf pin from the vertebral artery without embolization.

BACKGROUND: Foreign bodies traversing the aerodigestive tract lining into the surrounding soft tissues is a well-known entity. A 14-year-old girl was referred to our hospital after swallowing a pin that was not visualized by laryngoscopy, despite a neck film that localized it to the level of the larynx. METHODS: A CT scan demonstrated a bent pin piercing the left vertebral artery "through and through," and this was confirmed by angiography. The pin was extracted via an external approach to the neck without preoperative intravascular manipulation. RESULTS: Angiography immediately after the surgery demonstrated a stable thrombotic sleeve in the vertebral artery without further clot propagation or bleeding from the vessel wall. This is the first report of a "through and through" thrombotic sleeve in an artery. CONCLUSIONS: Simple surgical removal of a sharp foreign body from the vertebral artery without intravascular management may be a reasonable option.

Turban pin aspiration: new fashion, new syndrome.

OBJECTIVES/HYPOTHESIS: Turban pin aspiration syndrome is a new clinical entity afflicting young Islamic girls wearing a turban.The goal of this study was to present our experience in diagnosis and treatment of this new entity, define its clinical and epidemiologic features, and shed a new light on the role of fashion in the increased incidence. STUDY DESIGN: A retrospective study in a tertiary university hospital. METHODS: Review of clinical parameters and epidemiologic features of 26 patients diagnosed with turban pin aspiration syndrome admitted to the Hadassah-Hebrew University Hospitals in Jerusalem from 1990 to 2010. RESULTS: All patients were Muslim females with an average age of 16 years. In all cases, the history was positive for accidental aspiration. Most of the pins were located in the trachea (42%). In 20 cases, the pins were extracted by rigid bronchoscopy without major complications. Fluoroscopy-assisted rigid bronchoscopy was used successfully in three cases. In one case, the object was self-ejected by coughing before the bronchoscopy, and two patients were referred to the chest unit for thoracotomy. CONCLUSIONS: Clinicians should be aware of this distinct form of foreign body aspiration, its method of diagnosis, and extraction techniques. A cultural investigation showed a difference in the turban-fastening technique of young girls as compared with their mothers. Removal by rigid bronchoscopy is a safe method with a high success rate and should be considered as the preferred extraction method of choice.

Recurrent vascular leiomyoma of the larynx: clinical and histopathologic characteristics and treatment.

Laryngeal vascular leiomyomas are uncommon benign tumors that seldom recur following complete excision. The choice of excision procedure-via direct laryngoscopy or an open approach-is dictated by tumor size, the expected amount of blood loss, and any comorbidities the patient may have. We report an unusual case of a recurrent laryngeal vascular leiomyoma in a 64-year-old woman who also had a concurrent parathyroid adenoma and a history of breast carcinoma. A surgical resection via an external approach along with laser resection of a small glottic component was needed.

Identification of an Escherichia coli operon required for formation of the O-antigen capsule.

Escherichia coli produces polysaccharide capsules that, based on their mechanisms of synthesis and assembly, have been classified into four groups. The group 4 capsule (G4C) polysaccharide is frequently identical to that of the cognate lipopolysaccharide O side chain and has, therefore, also been termed the O-antigen capsule. The genes involved in the assembly of the group 1, 2, and 3 capsules have been described, but those required for G4C assembly remained obscure. We found that enteropathogenic E. coli (EPEC) produces G4C, and we identified an operon containing seven genes, ymcD, ymcC, ymcB, ymcA, yccZ, etp, and etk, which are required for formation of the capsule. The encoded proteins appear to constitute a polysaccharide secretion system. The G4C operon is absent from the genomes of enteroaggregative E. coli and uropathogenic E. coli. E. coli K-12 contains the G4C operon but does not express it, because of the presence of IS1 at its promoter region. In contrast, EPEC, enterohemorrhagic E. coli, and Shigella species possess an intact G4C operon.