Audiological Manifestations in Patients with Granulomatosis with Polyangiitis.

Background and Objectives: Granulomatosis with Polyangiitis (GPA) is a rare, autoimmune, multisystemic disease characterized by vasculitis and necrotizing granuloma that commonly affects the upper and lower respiratory tract and kidneys. Audiovestibular dysfunction in GPA diseases may have different clinical presentations. The aim of the present study was to evaluate hearing function in patients with GPA and to compare the results with a healthy control group. Materials and Methods: A total of 34 individuals participated in the study. The GPA group consisted of 14 participants, and the control group was composed of 20 healthy participants with no signs or symptoms of ear disease. The ages ranged from 18 to 65 years old, with a mean age of 43.8 years. The participants underwent a complete audiological evaluation using otoscopy, impedance audiometry, pure tone audiometry, speech audiometry-evaluation of speech thresholds, and speech recognition in quiet. Both ears were tested. All of the participants of the study were native Lithuanian speakers. Data were statistically analyzed using the Statistical Analysis System software SAS® Studio 3.8. A p value < 0.05 was regarded as statistically significant. Results: 92.85% of patients from the GPA group reported hearing-related symptoms: hearing loss, tinnitus, and fullness in the ears. The arithmetic means of all hearing thresholds at frequencies from 125 Hz to 8000 Hz were significantly higher in the GPA group. The results revealed statistically significant differences between the two groups in the Speech Detection Threshold, Speech Recognition Threshold, Speech Discomfort level, and Word Recognition Scores. Conclusions: The frequency of hearing loss, the average hearing thresholds, and speech thresholds were higher in GPA patients than in healthy individuals. The most common type of hearing loss was sensorineural. Audiological assessments should be considered during the routine evaluation of patients with GPA disease to prevent hearing-related disabilities.

Identification of 27 Novel Variants in Genes COL4A3, COL4A4, and COL4A5 in Lithuanian Families With Alport Syndrome.

Introduction: Alport syndrome (AS) is an inherited disorder characterized by hematuria, proteinuria, and kidney function impairment, and frequently associated with extrarenal manifestations. Pathogenic variants in COL4A5 usually cause X-linked Alport syndrome (XLAS), whereas those in the COL4A3 or COL4A4 genes are associated with autosomal dominant (AD) or recessive (AR) inheritance. To date, more than 3000 different disease-causing variants in COL4A5, COL4A3, and COL4A4 have been identified. The aim of this study was to evaluate the clinical and genetic spectrum of individuals with novel, pathogenic or likely pathogenic variants in the COL4A3-A5 genes in a previously unstudied cohort. Methods: In this study molecular analysis by next generation sequencing (NGS) was performed on individuals from a Lithuanian cohort, with suspected AS. The presence of AS was assessed by reviewing clinical evidence of hematuria, proteinuria, chronic kidney disease (CKD), kidney failure (KF), a family history of AS or persistent hematuria, and specific histological lesions in the kidney biopsy such as thinning or lamellation of the glomerular basement membrane (GBM). Clinical, genetic, laboratory, and pathology data were reviewed. The novelty of the COL4A3-A5 variants was confirmed in the genetic variant databases (Centogene, Franklin, ClinVar, Varsome, InterVar). Only undescribed variants were included in this study. Results: Molecular testing of 171 suspected individuals led to the detection of 99 individuals with 44 disease causing variants including 27, previously undescribed changes, with the frequency of 9/27 (33,3%) in genes COL4A5, COL4A3 and COL4A4 equally. Three individuals were determined as having digenic AS causing variants: one in COL4A3 and COL4A4, two in COL4A4 and COL4A5. The most prevalent alterations in genes COL4A3-5 were missense variants (n = 19), while splice site, frameshift, unknown variant and stop codon changes were detected more in genes COL4A4 and COL4A5 and accounted for 3, 3, 1 and 1 of all novel variants, respectively. Conclusion: Genotype-phenotype correlation analysis suggested that some variants demonstrated intra-familial phenotypic variability. These novel variants represented more than half of all the variants found in a cohort of 171 individuals from 109 unrelated families who underwent testing. Our study expands the knowledge of the genetic and phenotypic spectrum for AS.

The role of questioning environment, personality traits, depressive and anxiety symptoms in tinnitus severity perception.

Psychological factors have been described as important for tinnitus severity, but attempts to incorporate them in one picture are sparse. This study investigated to what extent traits (personality), states (depressive and anxiety symptoms), sociodemographic factors and questioning environment influence tinnitus severity perception and how they interplay. Data were obtained from 212 subjects in a survey that was undertaken in 2016 at Vilnius University hospital and via internet. Measures included the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Hospital Anxiety and Depression Scale (HADS), Big Five Personality Dimensions Scale and sociodemographic questions. A series of stepwise forward and multiple regression analyses were undertaken to discover how factors interconnect. Female gender, age, living in rural area, but not level of education, were found to be associated with THI and HADS. Total HADS score and of both subscales were linked to scores on THI, VAS scales and all personality traits, except agreeableness (and consciousness for anxiety). Anxiety was the most important predictor for tinnitus severity, followed by depressive symptoms. Only neuroticism from personality dimensions was a predictor of THI score, whereas THI scores did not predict scores on neuroticism. All results in scales were higher in the internet group, except agreeableness and neuroticism, while extroversion correlated negatively with THI score only in the hospital group. Tinnitus severity was highly correlated with depressive, anxiety symptoms and neuroticism. Respondents recruited through internet had higher scores on most parameters. Results emphasize the importance of psychological factors in tinnitus management.

Closed tympanoplasty in middle ear cholesteatoma surgery.

OBJECTIVE: To determine the effect of closed tympanoplasty surgery for middle ear cholesteatoma and to compare the postoperative results with the outcomes of canal-wall-down mastoidectomy. METHODS: Seventy patients with middle ear cholesteatoma were involved in the study. Pneumo-otoscopy, pure-tone audiometry, anamnestic and clinical data were evaluated before the surgery. Modified radical mastoidectomy was performed for 31 patients. Thirty-nine patients were treated with closed tympanoplasty surgery, including intact canal wall mastoidectomy, endaural atticotomy, lateral attic and aditus wall reconstruction and tympanoplasty. The follow-up examination was carried out 12 months after the surgery. The recurrence of cholesteatoma, otorrhea and hearing level were evaluated postoperatively. RESULTS: Otorrhea was estimated in 4 cases (10.3%) after closed tympanoplasty surgery and in 6 cases (19.4%) after modified radical mastoidectomy. Among the patients who were operated using closed tympanoplasty technique the middle ear cholesteatoma recurrence rate was 12.8% and among those, who underwent modified radical mastoidectomy recurrent disease occurred in 9.7% of the cases. The hearing improvement was found in 15 cases (38.46%) after closed tympanoplasty, while there was no hearing improvement after modified radical mastoidectomy. CONCLUSIONS: We conclude that despite the fact, that cholesteatoma recurrence rate after closed tympanoplasty is relatively high, this surgical method permits to preserve adequate hearing level and releases from postoperative cavity care problems as compared with modified radical mastoidectomy.

[Middle ear cholesteatoma: present-day concepts of etiology and pathogenesis]. / Siuolaikine vidurines ausies cholesteatomos etiologijos ir patogenezes samprata.

Since J. Cruveilhier described cholesteatoma as the "pearly" tumor of the middle ear in 1828, the pathogenesis of cholesteatoma remained controversial. It is accepted that cholesteatoma may be congenital or acquired. Several pathogenic mechanisms have been proposed to explain the pathogenesis of congenital cholesteatoma. Proposed theories include ectopic epidermis rest, ingrowth of meatal epidermis, metaplasia and reflux of amniotic fluid. Four basic theories present the pathogenesis of acquired cholesteatoma: invagination of the tympanic membrane (retraction pocket cholesteatoma), basal cell proliferation, epithelial in-growth through a perforation (the immigration theory) and squamous metaplasia of middle ear epithelium. The aim of the article is to review the recent literature dealing with problems of the etiopathogenesis and classification of cholesteatoma.