MMP-9 plasma level as biomarker of cochlear implantation outcome in cohort study of deaf children.

PURPOSE: If before cochlear implantation it was possible to assay biomarkers of neuroplasticity, we might be able to identify those children with congenital deafness who, later on, were at risk of poor speech and language rehabilitation outcomes. METHODS: A group of 40 children aged up to 2 years with DFNB1-related congenital deafness was observed in this prospective cohort study over three follow-up intervals (0, 8, and 18 months) after cochlear implant (CI) activation. Children were assessed for auditory development using the LittlEARS Questionnaire (LEAQ) score, and at the same time, measurements were made of matrix metalloproteinase-9 (MMP-9) plasma levels. RESULTS: There were significant negative correlations between plasma levels of MMP-9 at 8-month follow-up and LEAQ score at cochlear implantation (p = 0.04) and LEAQ score at 18-month follow-up (p = 0.02) and between MMP-9 plasma levels at 18-month follow-up and LEAQ score at cochlear implantation (p = 0.04). As already reported, we confirmed a significant negative correlation between MMP-9 plasma level at cochlear implantation and LEAQ score at 18-month follow-up (p = 0.005). Based on this latter correlation, two clusters of good and poor CI performers could be isolated. CONCLUSIONS: The study shows that children born deaf who have an MMP-9 plasma level of less than 150 ng/ml at cochlear implantation have a good chance of attaining a high LEAQ score after 18 months of speech and language rehabilitation. This indicates that MMP-9 plasma level at cochlear implantation is a good prognostic marker for CI outcome.

Longitudinal Changes in BDNF and MMP-9 Protein Plasma Levels in Children after Cochlear Implantation.

Congenitally deaf children who undergo cochlear implantation before 1 year of age develop their auditory skills faster than children who are implanted later. In this longitudinal study, a cohort of 59 implanted children were divided into two subgroups according to their ages at implantation-below or above 1 year old-and the plasma levels of matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF), and pro-BDNF were measured at 0, 8, and 18 months after cochlear implant activation, while auditory development was simultaneously evaluated using the LittlEARs Questionnaire (LEAQ). A control group consisted of 49 age-matched healthy children. We identified statistically higher BDNF levels at 0 months and at the 18-month follow-ups in the younger subgroup compared to the older one and lower LEAQ scores at 0 months in the younger subgroup. Between the subgroups, there were significant differences in the changes in BDNF levels from 0 to 8 months and in LEAQ scores from 0 to 18 months. The MMP-9 levels significantly decreased from 0 to 18 months and from 0 to 8 months in both subgroups and from 8 to 18 months only in the older one. For all measured protein concentrations, significant differences were identified between the older study subgroup and the age-matched control group.

Electro-Natural Stimulation in Partial Deafness Treatment of Adult Cochlear Implant Users: Long-Term Hearing Preservation Results.

BACKGROUND: Due to the constant development of technology and medicine, the eligibility criteria for cochlear implantation (CI) are undergoing gradual expansion. OBJECTIVES: To provide long-term hearing preservation (HP) results for partial deafness treatment (PDT) of a group of adults using electro-natural stimulation (ENS). METHODS: We examined a database of medical records of patients who underwent CI in a single ENT center. We identified 12 adults (3 men and 9 women) who fitted the PDT-ENS classification. To calculate HP, we used the -HEARRING consensus and conducted statistical analyses using SPSS v24. RESULTS: In the long-term follow-up, 7 of 12 patients had complete HP and the remaining 5 had partial HP. None of the patients experienced significant hearing impairment. A significant improvement in speech understanding in both quiet and noise conditions was also observed. CONCLUSIONS: The use of minimally invasive surgery leads to excellent HP results in PDT-ENS patients, enabling them to enjoy the benefits of good speech discrimination which they would be unable to get from traditional hearing aids. Our findings support extending the inclusion criteria for CI to include this new group of patients who would otherwise obtain only limited benefit from conventional hearing aids.

Cochlear implantation with the nucleus slim straight electrode in subjects with residual low-frequency hearing.

OBJECTIVES: To measure benefit in terms of speech recognition in quiet and in noise, and conservation of residual hearing in three groups of subjects implanted with the Nucleus Straight Research Array cochlear implant. This device incorporates the Nucleus Slim Straight electrode carrier designed to be easier to insert into the cochlea via the round window while potentially minimizing insertion trauma. DESIGN: The study was prospective, with sequential enrolment and within-subject repeated measures; 35 subjects were 15 to 84 years of age with varying levels of bilateral high-frequency HL. Subjects were divided into three groups (A, B, and C) according to preoperative air conduction hearing thresholds in the ear to implant at 500 Hz; A ≤ 50 (n = 11), 50 < B < 80 (n = 13), and C ≥ 80 (n = 11) dB HL. Speech recognition was assessed preoperatively and at intervals up to 1 year postimplantation. Hearing thresholds were monitored over time and CT scans were used to estimate electrode positions. RESULTS: Preoperative mean word recognition score was significantly greater for group A compared with group C in quiet (diff. 26.6%pts, p < 0.05), but not so in noise (diff. 7.9%pts, p = 0.72). However, a greater proportion of subjects in group A (81%) achieved a "worthwhile" gain in speech recognition score (>20%pts) in quiet compared with group C (63%). More importantly, for speech recognition in noise, all subjects in groups A and B achieved a >20%pts gain compared with only 73% in group C. Hearing in implanted ears was well conserved for low frequencies, both initially and up to 12 months postoperatively (15 dB median increase in thresholds 250 to 500 Hz). Only 3 of 35 (9%) cases lost all residual hearing in the implanted ear by 12 months. Where characteristic frequency corresponded to a position occupied by the electrode array, threshold increase was correlated with the preoperative hearing threshold (r = 0.7; p < 0.001) and closely approximated reported estimates of residual outer hair cell gain. For characteristic frequencies at positions apical to the electrode tip, the relation between threshold increase and residual hearing decreased in amplitude at 45 to 135 degrees (r = 0.42; p < 0.05), and disappeared at >135 degrees (r = 0.05; p > 0.05). CONCLUSION: Gains in speech recognition scores for subjects with better residual low-frequency hearing were greater or equal to those obtained by subjects with poorer residual hearing. Residual hearing after cochlear implantation with the Nucleus Slim Straight electrode array was well conserved across all three groups. It appears that the gain provided by outer hair cell function may be completely suppressed when an electrode array is in close proximity to the organ of Corti.

Partial deafness treatment with the nucleus straight research array cochlear implant.

INTRODUCTION: The Nucleus Straight Research Array (SRA) cochlear implant has a new 25-mm electrode carrier designed to minimize insertion trauma, in particular allowing easy insertion via the round window. The aims of this study were to measure preoperative to postoperative benefit in terms of speech recognition in quiet and in noise in three groups of patients (electrical complement, EC; electrical stimulation, ES; electro-acoustic stimulation, EAS) with varying levels of low-frequency hearing, and to evaluate the preservation of residual hearing after implantation with the SRA cochlear implant. METHODS: The study design was prospective with sequential enrolment and within-subject comparisons: 23 adult cochlear implant candidates were divided into three groups according to their level of preoperative residual hearing at 500 Hz (EC ≤50 dB; 50 dB < EAS < 80 dB; ES ≥80 dB). Monosyllabic word recognition using the SRA cochlear implant in combination with residual low-frequency hearing was assessed at 4 and 13 months after implantation. Hearing threshold levels were also monitored over time. RESULTS: Subjects across all three groups had significant improvements in speech recognition scores (i.e. >20 percentage points) both for listening in quiet (71% of subjects) and in noise (100% of subjects). The average score at 4 months after operation for words presented in quiet was 61.7%, and in 10 dB SNR noise 46.5%, compared to 34.4 and 10.6% preoperatively (p < 0.001). All subjects retained measurable hearing at 500 Hz in the implanted ear at 4 months after the operation; mean increases were 19, 29 and 1 dB for the EC, EAS and ES groups (n = 21). Across frequencies of 125-1000 Hz, the median increase in thresholds was 15 dB up to 13 months postoperatively (n = 15). CONCLUSIONS: Speech recognition performance of subjects with various levels of residual low-frequency hearing was significantly improved with the SRA cochlear implant. A high level and rate of hearing preservation was achieved with the SRA implanted using a round window surgical technique. Subjects with preoperative low-frequency hearing levels between 50 and 80 dB HL (EAS group) tended to lose more hearing than those with either better or worse hearing.

Adverse Audio-Vestibular Effects of Drugs and Vaccines Used in the Treatment and Prevention of COVID-19: A Review.

(1) Background: The purpose of this article is to review pharmacological treatments for COVID-19 (currently approved by the EMA (European Medical Agency) and FDA (Food and Drug Administration)) and highlight their potential audio-vestibular side-effects as an ototoxic adverse reaction. (2) Methods: Review of the available literature in the scientific databases PubMed, ResearchGate, Scopus, and ScienceDirect, and in summaries of product data sheets. (3) Results: In accordance with EBM (evidence-based medicine) the treatment of COVID-19 by using lopinavir/ritonavir, chloroquine and hydroxychloroquine, azithromycin, favipiravir, amantadine, oseltamivir, and ivermectin is no longer recommended for patients suffering from COVID-19 due to a lack of clinical data, publications, and recommendations. There were 39 publications and 15 summaries of product characteristics (as other sources of data) which were also used in this analysis. Adverse events could be permanent or disappear over time. Following treatment for COVID-19, the most frequent adverse audio-vestibular reactions reported in clinical trials and publications in the area of audiology and otorhinolaryngology were: dizziness, blurry vision with dizziness, nasopharyngitis, dysgeusia, and tinnitus. As far as vaccines are concerned, dizziness as an ototoxic effect was uncommon and occurs only in hypersensitive people who experience anaphylactic shock. (4) Conclusions: The ototoxicity of the drugs discussed here does not have as severe symptoms as the drugs used in the treatment of COVID-19 in 2020 (e.g., hydroxychloroquine), and relates mainly to disorders of the vestibulocochlear system. However, there is still a need to monitor ototoxic side-effects because of potential interactions with other ototoxic drugs. Many of the drugs approved by EMA and FDA are new, and not every side-effect is known.

Prospective cohort study reveals MMP-9, a neuroplasticity regulator, as a prediction marker of cochlear implantation outcome in prelingual deafness treatment.

Because of vast variability of cochlear implantation outcomes in prelingual deafness treatment, identification of good and poor performers remains a challenging task. To address this issue, we investigated genetic variants of matrix metalloproteinase 9 (MMP9) and brain-derived neurotrophic factor (BDNF) and plasma levels of MMP-9, BDNF, and pro-BDNF that have all been implicated in neuroplasticity after sensory deprivation in the auditory pathway. We recruited a cohort of prelingually deaf children, all implanted before the age of 2, and carried out a prospective observation (N = 61). Next, we analyzed the association between (i) functional MMP9 (rs20544, rs3918242, rs2234681) and BDNF (rs6265) gene variants (and their respective protein levels) and (ii) the child's auditory development as measured with the LittlEARS Questionnaire (LEAQ) before cochlear implant (CI) activation and at 8 and 18 months post-CI activation. Statistical analyses revealed that the plasma level of MMP-9 measured at implantation in prelingually deaf children was significantly correlated with the LEAQ score 18 months after CI activation. In the subgroup of DFNB1-related deafness (N = 40), rs3918242 of MMP9 was significantly associated with LEAQ score at 18 months after CI activation; also, according to a multiple regression model, the ratio of plasma levels of pro-BDNF/BDNF measured at implantation was a significant predictor of overall LEAQ score at follow-up. In the subgroup with DFNB1-related deafness, who had CI activation after 1 year old (N = 22), a multiple regression model showed that rs3918242 of MMP9 was a significant predictor of overall LEAQ score at follow-up.

Results of Hearing Screening in School-Age Children from Rural Areas of the Kujawsko- Pomorskie Region in Poland.

OBJECTIVE: There is a need for regular surveillance of the hearing of children, no matter what their age. Screening of the hearing of school children can be done quickly and cheaply using teleaudiology. The primary aim of this study was to identify children who showed a suspected hearing impairment from rural areas of the Kujawsko-Pomorskie region and refer them for further audiological testing. A secondary aim was to estimate the prevalence of hearing loss in those children. METHODS: There were 4754 children, made up of 1840 children aged 6-7 years old and 2914 children aged 12-13 years old. Pure-tone air conduction thresholds were obtained at 0.5-8 kHz. Audiometric test was supplemented by results of a brief questionnaire filled in by parents. RESULTS: Of the 4754 children, 618 (13%) failed screening and were referred for detailed audiological diagnostics. The prevalence of hearing loss was estimated to be 7% and was significantly higher (OR = 2.12) in the group aged 6-7 y/o (10.1%) than in the group aged 12-13 y/o (5.0%). In our study the estimated prevalence of HL was twice as high in children aged 6-7 y/o (10.1%) than in children 12-13 y/o (5.0%). This difference was also evident in another study of Polish children from rural areas, where the prevalence of HL was 11.4% in younger children (6-9 y/o) and 5.5% in older children (12-13 y/o). CONCLUSION: Large numbers of school-age children in rural areas have hearing problems. It is recommended that a hearing screening program in primary schools based on e-health solutions should be adopted.

Functional Polymorphism of MMP9 and BDNF as Potential Biomarker of Auditory Neuroplasticity in Prelingual Deafness Treatment With Cochlear Implantation-A Retrospective Cohort Analysis.

Genetic biomarkers of neuroplasticity in deaf children treated with cochlear implantation (CI) might facilitate their clinical management, especially giving them better chances of developing proficient spoken language. We investigated whether carrying certain variants of the genes encoding matrix metalloproteinase MMP9 and neurotrophin brain-derived neurotrophic factor (BDNF), involved in synaptic plasticity, can be taken as prognostic markers of how well auditory skills might be acquired. Association analysis of functional MMP9 rs3918242 and BDNF rs6265 variants and the child's auditory development measured at CI activation and 1, 5, 9, 14, and 24 months post CI activation with LittlEARS Questionnaire (LEAQ) was conducted in a group of 100 children diagnosed with DFNB1-related deafness, unilaterally implanted before the age of 2 years. Statistical analysis in the subgroup implanted after 1 year of life (n = 53) showed significant association between MMP9 rs3918242 and LEAQ scores at 1 month (p = .01), at 5 months (p = .01), at 9 months (p = .01), and at 24 months (p = .01) after CI activation. No significant associations in the subgroup implanted before 1 year of life were observed. No significant associations between the BDNF rs6265 and LEAQ score were found. Multiple regression analysis (R2 = .73) in the subgroup implanted after 1 year of life revealed that MMP9 rs3918242 was a significant predictor of treatment outcome. In conclusion, C/C rs3918242 MMP9 predisposes their deaf carriers to better CI outcomes, especially when implanted after the first birthday, than carriers of C/T rs3918242MMP9.

Hearing Screening among First-Grade Children in Rural Areas and Small Towns in Malopolskie Voivodeship, Poland.

Undiagnosed hearing deficits hamper a child's ability to learn. Hearing screening in school aged children helps detect educationally significant hearing loss and prevents negative impacts on academic achievement. The main purpose of this study was to improve early detection and assess the incidence of hearing disorders in first-graders from rural areas and small towns in the Malopolskie Voivodeship of Poland. There were 5029 children aged 6-7 years. Hearing thresholds were measured over the frequency range 0.5-8 kHz. A result was considered positive (abnormal) if the hearing threshold was worse than 20 dB HL at one or more frequencies. The prevalence of hearing loss was estimated in terms of four-frequency hearing loss, high-frequency hearing loss, and low-frequency hearing loss. Parents filled in a brief audiological questionnaire. The analysis was performed using IBM SPSS Statistics, version 24. Of all the children, 20.5% returned a positive result and were referred for further audiological diagnoses. The estimated prevalence of hearing loss was 11.6%, made up of 6.5% with FFHL, 7.6% with HFHL, and 8.2% with LFHL. This study showed that large numbers of children in the district had hearing problems. Adoption of hearing screening in primary schools is recommended as a routine procedure within preventive pediatric health care.

[Endovascular and surgical associated treatment of post-traumatic epistaxis]. / Skojarzone leczenie endowaskularne i chirurgiczne pourazowych krwawien z nosa.

We report on two cases of patients, in whom endovascular embolization of the maxillary artery and next surgical ligation of the anterior ethmoidal artery was performed due to posttraumatic intracrable epistaxis. In those patients, conservative treatment failed, hence endovascular embolization was made. Due to persisted bleeding, right anterior ethmoidal artery were surgically ligated in both patients. After the procedures, bleeding completely stopped.

[Identification of human papilloma viruses (HPV) in inflammatory states and ear neoplasms]. / Identyfikacja wirusów ludzkich brodawczaków (HPV) w stanach zapalnych i nowotworach uszu.

INTRODUCTION: Human Papilloma Virus has a strong relation to oropharyngeal mucosa and is considered to be responsible for a wide range of upper respiratory tract pathologies, like laryngeal papilloma. There's a hypothesis, that it plays a significant role in middle ear chronic inflammations and neoplasm's. MATERIAL AND METHODIC. The examination was carried on a group of 53 patients, 39 of which was suffering from granulation tissue chronic otitis media, 7-cholesteatomatous otitis media, 6--middle ear malignant neoplasm, and 1 middle and/or external ear benign neoplasm. The control group consisted of 5 patients operated on: otosclerosis--4 cases and post-traumatic tympanic membrane perforation--1 case. The material was postoperative tissue, like polyps, inflammatory granulation tissue, cholesteatoma masses and malignant neoplasm's tissue. RESULTS: In the whole group of 53 examined cases, HPV DNA was confirmed in 22 cases (41.5%), in that group oncogenic types 16 or 18 in 12 cases (22.6%), and in 14 cases (26.4%) types 6 or 11. In a group of chronic granulomatous otitis media DNA characteristic for Papilloma was identified in 12 cases (25.6%), in it in 9 cases DNA HPV type 6 or 11 was confirmed, and in 7 cases type 16 or 18. Among cholesteatomatous chronic otitis media HPV DNA types 6 or 11 was identified in 70%. In every case of middle ear malignant neoplasm a presence of high-risk DNA Papilloma types 16 or 18 was confirmed. In any case of control group HPV DNA was detected. CONCLUSIONS: The results has been compared with other authors examinations and it is claimed that they confirm the observation, that Human Papilloma Viruses may be a factor, that might play an important role in pathology of chronic otitis media and ear neoplasm's. It is concluded, that differences in percentages of HPV presence in chronic inflammations (70%) and ear neoplasm's may be explained by viral co-infection during bacterial c. o. m. Viral infection probably evolves carcinogenesis, which leads to a neoplastic growth.

[Osteosarcoma of the larynx]. / Osteosarcoma krtani.

The authors present a case of rare laryngeal neoplasm--osteosarcoma, which generated many diagnostic and treatment difficulties. Its main cause was nonspecific symptoms and laryngoscopic view, positive tuberculous history and positive tuberculosis tests. The first histopathological examination was "angioleiomyoma exulcerans, chronic inflammation and granulation." No cancer nor tuberculosis was found". After the physiologic consultations and with positive tuberculin test the tuberculocidal treatment was applied, but it bought no success. The larynx was split then, intraoperative histopathological examination gave the result: "Cellulae carcinomatosae". The total laryngectomy was performed. Postoperative immunohistochemical examination was "Osteosarcoma of larynx". The patient was not evaluated for radio- or chemotherapy. Admitted to the hospital after 5 months with neck tumor and reactional lymph nodes by the right side of the neck. Crile's operation was performed. During the postoperative course some metastatic lymph nodes on the left side of the neck and in lungs were detected. Patient noted to chemotherapy.

[Prevalence of conductive hypoacusis in children aged 5-9 years old from rural area in Poland--prospective screening of healthy subjects]. / Wystepowanie niedosluchu przewodzeniowego w grupie dzieci 5-9-letnich w populacji wiejskiej--prospektywne badania przesiewowe dzieci zdrowych.

Otitis media with effusion (OME) is a process, which goes on by inner side of intact tympanic membrane. Oligosymptomatic and deceitful course is characteristics for this disease. Fluid filling middle ear structures causes long-lasting hypoacusis. Chronic consequences of the OME are morphologic changes within the middle ear, especially in the tense part of the tympanic membrane, causing strengthened conductive hypoacusis. The OME morbidity peak falls in 3-6 year of life, which is the period of the most intense development of the child and speech creation. Discreet symptoms, like fullness and feeling of fluid movement, not advanced hypoacusis, causes many problems in putting proper diagnosis. There should be aimed at quick detection of these symptoms, otherwise long persisting hypoacusis can have permanent negative influence on child's development. The aim of this study was to show the effectiveness of screening in population of children in their pre-elementary school and at the elementary school, focused on discreet pathology of the middle ear (OME) and low grade conductive hypoacusis. The study has a prospective character. Screening has covered a group of 927 children, aged 5-10. Examination concerned a population of healthy children, attending pre-elementary school and first classes of elementary school. Past otiatric history was the first step of diagnostic process, followed by full ENT examination and tympanometry. Special stress was laid on collecting medical history directed on the existence of discreet symptoms, like: low-grade hypoacusis manifested by some elements of child's behaviour (non responding on instructions, louder speaking, higher volume in TV-set), articulation disorders, difficulties in communication and problems at school. A group of 116 children actually presenting aural complaints lasting several weeks to several years were separated from the while examined group. Every 10th child from analyzed population submitted hypoacusis, 32 children had discreet symptoms, which allows to suspect hypoacusis. 330 children manifested otoscopic changes, which frequency was proportional to the time that aural symptoms have been lasting and correlate with other complaints, such as: allergy, rhinitis, sleep with open mouth, adenoidal hypertrophy. Pathological results of tympanometry was obtained in 23.3% of examined population, 16.6% made children, who neither actually, neither in anamnesis had ENT complaints. It is important to emphasize that age analysis in examined population shows directly that children in their 6th year of life are the group which should be comprised by screening on middle ear pathology.