Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Audiologic Measures in an Indigenous Community with A2ML1- and FUT2-Related Otitis Media.

Background: Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare A2ML1 variants and a common FUT2 variant underwent additional phenological testing. In this study, we describe the audiologic profiles in A2ML1- and FUT2-related otitis media and the validity of otoscopy and genotyping for A2ML1 and FUT2 variants in screening for otitis media and hearing loss. Method: We analyzed A2ML1 and FUT2 genotypes together with demographic, otologic and audiologic data from tympanometry and hearing level assessments of 109 indigenous individuals. Results: We confirmed previous findings of a spectrum of nonsyndromic otitis media as associated with A2ML1 variants. A2ML1 and FUT2 variants were associated with high-frequency hearing loss at 4000 Hz. As expected, young age was associated with flat tympanograms, and eardrum perforations due to chronic otitis media were associated with severe-to-profound hearing loss across frequencies. Adding A2ML1 or FUT2 genotypes improved the validity of otoscopy as a screening test to rule out moderate-to-profound hearing loss. Conclusion: Continued multi-disciplinary management and audiologic follow-up using tympanometry and screening audiometry are needed to document and treat otitis media and prevent permanent hearing loss in the indigenous community.

Otologic and vestibular symptoms in COVID-19: A scoping review.

Background: Otologic and vestibular symptoms have been seen in patients confirmed to have COVID-19 disease. Further discussion of these symptoms may provide insight into short- and long-term management for these patients. Objective: The aim of this review was to describe the otologic and vestibular symptoms that present in patients with COVID-19. The primary outcomes of this review were onset, duration and clinical outcomes of these symptoms. Sources of Evidence: Pub Med, APAMed Central, Herdin, CINAHL, Scopus, Springer Link, ProQuest Coronavirus Research Database, and Google Scholar were searched for the articles to be included. Eligibility Criteria: Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss, ear pain, ear discharge, otitis media, vertigo, or tinnitus. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes. Results: The majority of patients who experienced hearing loss (68%), tinnitus (88%), vertigo/dizziness (30%), ear pain (8%), and discharge (100%) did so within a month of experiencing the typical symptoms of COVID-19. A majority also experienced complete resolution of their symptoms within 2 weeks. Standard treatment for COVID-19 was usually provided but when specific diagnoses are made for these symptoms (e.g., sudden sensorineural hearing loss, otitis media, vestibular neuritis), they are treated in the same manner as one would for non-COVID-19 cases, in addition to the management for COVID-19. In certain cases, there may be a need for additional work-up to rule out other causes. Conclusions: Otologic and vestibular symptoms were present in COVID-19 patients, majority as part of the systemic nature of the disease. The onset, duration, and course were consistent with the natural history of a systemic viral infection. COVID-19 should be considered in any patient with a new-onset hearing loss, tinnitus, or vertigo/dizziness, even in the absence of infectious or respiratory symptoms.

Determining concordance and cost impact of otoacoustic emission and automated auditory brainstem response in newborn hearing screening in a tertiary hospital.

OBJECTIVE: This study compared otoacoustic emission (OAE) and automated auditory brainstem response (AABR) in terms of concordance and cost impact for newborn hearing screening (NBHS) in the Philippine setting. METHODS: This was a prospective observational study to assess concordance between OAE and AABR involving 253 infants. Each infant underwent OAE and AABR testing. Infants who passed both tests were not required to follow up for additional testing. Infants who failed in any test were scheduled for repeat screening and diagnostic ABR after 1 month. Concordance was computed using B-statistic. FOR COST ANALYSIS: 4 scenarios were compared to 1-step both tests scenario: (1) OAE alone, (2) AABR alone, (3) 2-step OAE, and (4) 2-step AABR in terms of number of infants with hearing loss (HL) detected, cost of diagnosis, and economic loss from lack of treatment. RESULTS: There was high concordance between OAE and AABR (B-statistic = 0.8). AABR had a higher refer rate (18.58%) than OAE (10.27%) but higher number of detected babies with HL. Cost analysis favored an AABR alone scenario while the 2-step OAE protocol fared poorly. CONCLUSION: A change from 2-step OAE to AABR alone is worth considering in our institution.

Temporal Bone Chondroblastoma: Systematic Review of Clinical Features and Outcomes.

OBJECTIVE: Chondroblastoma is an uncommon benign neoplasm of cartilaginous origin usually involving the long bones. The temporal bone is a rare location for this tumor. The clinical profile, optimal medical and surgical management, and outcomes of treatment for temporal bone chondroblastoma remain unknown. METHODS: We performed a systematic review of the SCOPUS, PubMed, and CENTRAL databases for case reports and case series on patients with histopathologically proven temporal bone chondroblastoma. Data on demographics, clinical manifestation, surgical management, adjuvant treatment, and outcome on last follow-up were collected. RESULTS: A total of 100 cases were reported in the literature, including one described in the current study. The mean age of patients was 42.3 years (range, 2-85 years), with a slight male predilection (1.3:1). The most common clinical manifestations were otologic symptoms (e.g., hearing loss [65%], tinnitus, and otalgia) and a palpable mass. Surgical excision was performed in all cases, with gross total excision achieved in 58%. Radiation therapy was performed in 18% of cases, mostly as adjuvant treatment after subtotal excision. There were no deaths at a median follow-up of 2 years. Among the patients with detailed status on follow-up, 58% had complete neurologic recovery, 38% had partial recovery, and 4% had progression of symptoms as a result of tumor recurrence. CONCLUSIONS: Temporal bone chondroblastoma has a distinct clinical profile from chondroblastoma of long bones. Surgery is the mainstay of treatment, and radiation therapy may be given after subtotal excision. Outcomes are generally favorable after treatment.

Prevalence and reasons for non-follow-up of newborns with "refer" results on initial hearing screening

OBJECTIVE: To determine the prevalence rate of follow-up among infants who had a "refer" result on initial newborn hearing screening and to identify reasons for default by parents or guardians.METHODS:Design: Cross-Sectional StudySetting: Tertiary National University HospitalParticipants: 79 parents or guardians whose newborns obtained a "refer" result on initial hearing screening were interviewed over the phone.RESULTS: Among those babies who had a "refer" result on initial hearing screening, 51% followed up for repeat testing. The most common reasons for non-follow up by parents or guardians include being busy, distance from the hospital and baby's health condition.CONCLUSIONS: The follow-up rate in this study is higher compared to previous figures (27%), but is still below target. The reasons for non-follow-up obtained suggest problems may exist on all levels of the healthcare system. Appropriate solutions to address these problems should be explored.

A cross-sectional triangulation analysis of the knowledge, attitudes and practices of patients from the endocrinology clinic of the Philippine General Hospital on the use of herbal dietary supplements

OBJECTIVE: This study aimed to determine the knowledge, attitudes and practices (KAP) of a selected population of patients on herbal dietary supplements (HDS).METHOD: Methodological triangulation was used to generate a conceptual framework on HDS KAP. A survey of 175 patients was performed to measure knowledge and attitudes regarding HDS and SPSS was used for data analysis. Inverviews and focus group discussions (FGDs) were conducted to further explore the attitudes and practices, and constant comparison method was used for analysis of responses.RESULTS: Respondents were generally aware of HDS. Majority of survey respondents believed that HDS are different from conventional drugs (52.0%, pThe attitude toward HDS was generally positive. Majority (64.0%, pAmong the survey respondents, only 22% were HDS users. Family was shown to promote use while cost deterred their use.CONCLUSION: Individual knowledge and attitudes on HDS exert significant influence toward HDS practices. Factors that promote use are poor knowledge and positive attitudes toward HDS. Good knowledge seems to lead to judicious use or non-use.

Granulation tissue mimicking a glomus tumor in a patient with chronic middle ear infection

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> To present an unusual cause of pulsatile tinnitus, presenting in a young adult suffering from chronic recurrent foul-smelling discharge from the same ear.<br /><strong>METHODS:</strong><br /><strong>Design:</strong> Case Report<br /><strong>Setting:</strong> Tertiary National University Hospital<br /><strong>Patient:</strong> One<br /><strong>RESULTS:</strong> A 24 year-old woman presented with pulsatile tinnitus on a background of chronic recurrent foul-smelling discharge. Clinico-radiologic findings seemed consistent with a glomus tympanicum coexisting with chronic suppurative otitis media with cholesteatoma. She underwent tympanomastoidectomy with excision of the mass. Histopathologic evaluation revealed the mass to be granulation tissue.<br /><strong>CONCLUSION:</strong> Pulsatile tinnitus is rarely associated with chronic middle ear infection. Granulation tissue arising at the promontory may mimic glomus tumors when accompanied with this symptom. Despite this revelation, it would still be prudent to prepare for a possible glomus tumor intraoperatively so that profuse bleeding and complications may be avoided.</p>