Bilateral Hearing Research Articles

Bilateral Permanent Childhood Hearing Loss and Health-Related Quality of Life in Adolescence.

Little is known about the impact of bilateral permanent childhood hearing loss (PCHL) on health-related quality of life (HRQoL). The objective of this study was to describe preference-based and non-preference based HRQoL outcomes in adolescence, from both self and proxy perspectives, amongst participants of the Hearing Outcomes Project. The Health Utilities Index Marks II (HUI2) and III (HUI3) and the PedsQLTM Version 4.0 Generic Core Scales were used to measure HRQoL based on self and parent proxy reports in 114 adolescents aged 13–19 years, 76 with bilateral PCHL and 38 with normal hearing, recruited from a population sample that was followed up from birth to adolescence. Descriptive statistics and multivariable analyses were used to estimate the relationship between severity of PCHL and HRQoL outcomes. PCHL was associated with decrements in mean multi-attribute utility score that varied between 0.078 and 0.148 for the HUI2 (p = 0.001) and between 0.205 and 0.315 for the HUI3 (p < 0.001), dependent upon the national tariff set applied and respondent group. Multivariable analyses revealed that, after controlling for clinical and sociodemographic covariates, mean HUI3 multi-attribute utility scores were significantly lower in adolescents with moderately severe, severe and profound hearing loss than in adolescents with normal hearing. Significant differences in physical functioning, social functioning, psychosocial functioning and total PedsQLTM scores were only observed when assessments by parents were relied upon, but these dissipated in the multivariable analyses. Bilateral PCHL is associated with poorer HRQoL outcomes in adolescence. Further studies conducted are needed to understand the trajectory and underpinning mechanisms of HRQoL outcomes following PCHL.

MO1023BARDET-BIEDL SYNDROME OR SENIOR-LOKEN SYNDROME? GOING BEYOND THE OBVIOUS

Abstract Background and Aims Nephronophthisis (NPHP), a ciliopathy which almost always causes end-stage kidney disease (ESKD), may have extrarenal symptoms such as Bardet-Biedl syndrome (BBS) and Senior-Loken syndrome (SLS), and these are called NPHP-related ciliopathies (NPHP-RC). Bardet-Bield syndrome and SLS share similar clinical features, so that definitive diagnosis might depend on genetic analysis. Bardet-Bield syndrome diagnosis is typically based on clinical manifestations, which comprise, for example, renal defects, polydactyly, obesity, retinitis pigmentosa (RP), learning difficulties, in addition to secondary manifestations such as development delay, speech defects, hypertension, among others. Senior-Loken syndrome classical encompasses familial NPHP and RP; additional variable features can include skeletal, liver, neurologic and other visual defects, as well as obesity. NPHP genes are the most commonly affected in NPHP. Although disruption of the NPHP5 and NPHP6 genes are the most frequent cause of SLS, at least variants in ten genes have been reported. We present a case of a young girl clinically diagnosed with BBS, later known to be a SLS based on genetic analysis, revealing an unusual affected gene. Method We reviewed this case based on medical records. Results The patient presented with polydactyly at birth and pre-obesity in the first six months of age. At the age of 4 years she was first evaluated by ophthalmology due to reduced visual acuity which evolved unfavorably with severe generalized retinal dysfunction and moderate maculopathy at the age of 9 years. Delayed development and poor social skills were increasingly evident, as wells as short stature, small hands and dysmorphic facial features. At the age of 12 years bilateral transmission hearing loss was diagnosed and two years later she was referred to Endocrinology due to hirsutism, stretch marks and cushingoid facies. In this context, blood work was performed and surprisingly revealed plasma creatinine of 2.19 mg/dL and urea of 65 mg/dL. Kidney ultrasound revealed reduced dimensions and increased parenchymal echogenicity; an obstructive component was excluded. She rapidly progressed to ESKD and dialysis dependence. Bardet-Biedl syndrome was considered. She was referred for transplant assessment and underwent genetic testing. A homozygous likely pathogenic variant was identified in TRAF3IP1 gene, compatible with SLS 9 (autosomal recessive inheritance). Conclusion Although phenotype-based diagnosis was common in ciliopathies, genetic testing is now regularly used for definitive diagnosis. Mutations in the geneTRAF3IP1 were only recently described, particularly in patients presenting with NPHP, RP, skeletal defects, hepatic fibrosis and hexadactyly; ESKD is frequent between 3 and 16 years and SLS is formally associated. Our patient had several clinical manifestations suggestive of BBS, and presumptive diagnosis was assumed (although noticeable phenotypic overlap with SLS exists). Genetic analysis was crucial; the identified mutation in TRAF3IP1 justifies some of the extra-SLS/BBS-like manifestations. Patients must be monitored carefully, namely related to ESKD and extrarenal manifestations; there is also the need for segregation analysis (divorced parents and half-brothers). Ultimately this case represents a consequence of genetics evolution, with a wide genetic and clinical variability now described within these syndromes.

MO313A CASE OF ALPORT SYNDROME WITH PREGNANCY-RELATED ATYPICAL HEMOLYTIC UREMIC SYNDROME, AND CRESCENTIC GLOMERULONEPHRITIS

Abstract Background Thrombotic microangiopathy (TMA) is one of the most important complications in pregnant patients with chronic kidney disease (CKD) causing clinical deterioration. However, little is known about the pregnancy course in women with Alport syndrome (AS). Case A 28-week pregnant, 22-year-old woman was admitted to our clinic because of widespread edema. Her medical history was notable only for hearing impairment. On examination, vital signs were normal except for the blood pressure (150/90 mmHg). There were diffuse crackles at the lung bases, and 3+ pitting edema in both legs. Lab results revealed heavy proteinuria with 11 gr/day and isomorphic erythrocytes with granular casts in microscopic urine examination. An emergency c-section was performed due to severe preeclampsia at 30 weeks’ gestation. After delivery, her edema did not improve, serum creatinine and lactate dehydrogenase levels elevated, anemia and thrombocytopenia developed (Table 1). Additional tests revealed negative Coombs test, schistocytes on peripheral smear and normal ADAMTS13 level. There was no pathology in serological studies. She received four sessions of plasmapheresis therapy, and with the diagnosis of aHUS, eculizumab therapy was started. Despite improving thrombocytopenia and anemia, serum creatinine levels continued to rise and her urine output decreased. A kidney biopsy was performed (Figure 1). In the light microscopy, 11 of 15 glomeruli had circumferential cellular crescents and 4 had partial cellular crescents. The sample had no findings consistent with TMA. No staining was seen with IgG, IgA, IgM, C3, C1q, κ and λ in immunofluorescence. Further evaluation of hearing impairment revealed bilateral sensorineural hearing loss. A homozygous mutation was identified on COLA4 gene, while homozygous polymorphism on complement factor H (CFH) c.1204C&amp;gt;T and heterozygotic polymorphisms on CFH c.2808G&amp;gt;T and c.3148A&amp;gt;T were revealed. After discharge, her kidney function remained poor requiring maintenance hemodialysis despite 6 months of eculizumab therapy. Discussion Alport syndrome is a genetic disease with the triad of hematuria, sensorineural hearing loss, and ocular symptoms due to the defect in the synthesis of α3, α4 and α5 chains of Type 4 collagen. The increase in proteinuria, hypertension and the presence of CKD are shown as poor prognostic factors for both maternal and fetal health in pregnant women with AS. However, crescentic glomerulonephritis is not the classical biopsy finding of AS. In a few studies, crescents in AS have been reported to correlate with rapid disease progression. There is increasing knowledge that the complement system is involved in the pathogenesis of pauci-immune crescentic GN. High plasma c3a, c5a, c5b-9, Bb and low plasma properdin levels were found to show alternative complement activation and correlate with disease activity in pauci-immune crescentic GN patients. Few reports show that anti-complement therapies might be an option in these cases. Although our case’s kidney functions did not improve on eculizumab, we conclude that the polymorphisms in the complement genes may have induced crescent formation in the presence of pregnancy and abnormal glomerular structure due to AS. Conclusion Here we presented a case with AS complicated by aHUS and crescentic GN. Given this complex combination of rare causes of acute kidney injury, detailed clinical evaluation is of great importance in the evaluation of acute kidney injury during pregnancy.

Prvé skúsenosti s implantátom pre kostné vedenie zvuku Sophono

ntroduction: Bone conduction implants are currently used for rehabilitation of conductive and mixed hearing loss as well as for single sided deafness. A growing number of these implants available on the market increases requirements on detailed knowledge on their technical properties, and on their advantages and disadvantages in clinical practice. Sophono is one of the recent members in this implant group. The aim of the study is to summarize our first experiences with Sophono at our implantation center in Bratislava. Patients and methods: We present data of the first two adult patients who underwent Sophono implantation. Both suffered from bilateral conductive hearing loss of different etiology. We focused on their audiological functional outcomes, basic surgical aspects and subjective assessment by the patients. Results: In free field tone audiometry with the implant, both patients achieved improvement of hearing thresholds by 21.25 dB and 31.25 dB, respectively. In speech tests with and without noise, we also demonstrated a clear benefit of the implant, which was in a narrow relationship with the degrees of their hearing loss: speech discrimination scores in noise were 30% and 60% in patients 1 and 2, respectively. The surgical procedure in Sophono implantation is relatively simple and does not include any work on middle ear structures. Patient satisfaction with the implant does not always correspond to the measured functional outcomes. Conclusion: The Sophono implant represents a suitable option for rehabilitation of conductive and mixed hearing loss as well as single sided deafness in selected patients. The candidate selection is always based on comprehensive assessment in which the audiological results are an elementary criterion, but definitely not a single one. Keywords: Sophono – implantation – conductive hearing loss

Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterised by the growth of numerous tumour-like malformations in many parts of the body including skin, kidneys, brain, lung, eyes, liver, and heart. Mutations in the TSC1 or TSC2 genes have been reported to cause disruption in the TSC1-TSC2 intracellular protein complex, causing over-activation of the mammalian target of rapamycin protein complex. In this study, we present a 3-month-old male infant diagnosed with tuberous sclerosis, bilateral neurosensorial hearing loss, Wolff-Parkinson-White syndrome on electrocardiography, multiple cardiac rhabdomyomas with severe stenosis in the left ventricular outflow tract, who responded well to the Everolimus therapy.

Basilar artery occlusion presenting as sudden bilateral deafness: a case report

BackgroundMost sudden-onset hearing loss is due to otolaryngologic- and very rarely to cerebrovascular disease. We report a woman with sudden bilateral sensorineural hearing loss. This case suggests that even in the absence of brainstem or cerebellar signs, magnetic resonance imaging (MRI) and MR angiography (MRA) should be performed since such studies may reveal signs of life-threatening vertebrobasilar artery occlusion.Case presentationA 73-year-old Japanese woman with a history of hypertension, hyperlipidemia, and atrial fibrillation who suffered bilateral deafness with vertigo and vomiting was transferred from a local hospital to our department. On admission her consciousness was clear and vertigo was absent. Neurological examination revealed only bilateral sensorineural hearing loss. Head computed tomography (CT) returned no significant findings. The next morning she gradually developed severe drowsiness. Diffusion-weighted MRI demonstrated acute cerebral infarction in the brainstem and bilateral cerebellum; MRA showed basilar artery occlusion due to a cardioembolic thrombus. Revascularization was obtained by endovascular treatment. However, her condition worsened progressively during the following hours. CT revealed new brainstem lesions, massive cerebellar swelling, and obstructive hydrocephalus. She died on the second day after her admission.ConclusionsWhen hearing loss is due to vertebrobasilar occlusive disease, the prognosis is very poor. We suggest that vertebrobasilar stroke be suspected in patients with bilateral sensorineural hearing loss who present with risk factors for stroke such as atrial fibrillation and other neurologic signs.

Neonatal Screening for Congenital Hearing Loss in the North of Jordan; Findings and Implications.

Background:Congenital hearing loss is one of the important illnesses that affect newborns. Early diagnosis and treatment are a challenge for medical authorities in developing countries to improve children's functional, intellectual, emotional, and social abilities. We aimed to study the prevalence of congenital hearing loss in northern Jordan community and identify factors that could affect hearing screening protocol.Methods:Prospective cross-sectional study of 1595 infants born in our hospital underwent hearing screening tests. Totally, 104 were tested in NICU and the rest examined in the nursery room using Otoacoustic emission (OAE) test as a primary testing tool. The patients were followed in the three hearing screening phases. Factors affecting screening results were studied and analyzed.Results:The total number of newborns who didn't pass the first OAE test in one or both ears were 90 (5.6%); 69 from the nursery group and 21 from the NICU group. In the 2nd screening phase 21 (23.3%) didn't attend the appointment. Sixty-four passed the second screening OAE test. Five newborns (5.6%) had a second refer result in one or both ears and referred for a diagnostic ABR test. Three infants passed the test and two found to have bilateral hearing loss.Conclusions:Hearing screening test is conducted via a 3-phases-protocol. OAE is used in the first two phases and ABR in the third phase. Hearing results is significantly affected for infants admitted to NICU. The following factors increase OAE fail response: mechanical ventilation for more than 5 days, Hyperbilirubinemia, associated congenital anomalies. Mode of delivery doesn't have statistical significance on hearing screening results.

Распространенность и классификация асимметричных форм сенсоневральной тугоухости в старшей возрастной группе

The significance of asymmetric sensorineural hearing loss (ASNHL) is due to a special approach to diagnosis, followed by the process of hearing aids and auditory rehabilitation. Currently, there is no standard audiometric criterion for determining the forms of asymmetry, which significantly affects the assessment of the prevalence of ASNHL. The study aimed to assess the prevalence and classification of ASNHL forms in the older age group using two methods of calculation: 1) the difference in the average hearing threshold at speech frequencies (in the range of 0,5–4 kHz) ≥15 dB was detected in 14,14% of cases; 2) the different degree of hearing loss, according to the International classification, in the right and left ear was 35,98%. In most cases, asymmetry was manifested by bilateral sensorineural hearing loss of varying severity, prevailing in the group of long-livers – 82,6%. Given the potentially high prevalence of asymmetry depending on the audiological criterion, the results of the work are a reason for further research in the development of a unified method for verifying a clinically significant form of ASNHL.

A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome

We report the first case of Waardenburg syndrome type 4C and Kallmann syndrome in the same person. The patient, a Japanese girl, presented with bilateral iris depigmentation, bilateral sensorineural hearing loss, Hirschsprung disease, hypogonadotropic hypogonadism, and anosmia. We identified a novel SOX10 variant, c.124delC, p.Leu42Cysfs*67.

A novel MYH14 mutation in a Chinese family with autosomal dominant nonsyndromic hearing loss

BackgroundMYH14 gene mutations have been suggested to be associated with nonsyndromic/syndromic sensorineural hearing loss. It has been reported that mutations in MYH14 can result in autosomal dominant nonsyndromic deafness-4A (DFNA4).MethodsIn this study, we examined a four-generation Han Chinese family with nonsyndromic hearing loss. Targeted next-generation sequencing of deafness genes was employed to identify the pathogenic variant. Sanger sequencing and PCR-RFLP analysis were performed in affected members of this family and 200 normal controls to further confirm the mutation.ResultsFour members of this family were diagnosed as nonsyndromic bilateral sensorineural hearing loss with postlingual onset and progressive impairment. A novel missense variant, c.5417C > A (p.A1806D), in MYH14 in the tail domain of NMH II C was successfully identified as the pathogenic cause in three affected individuals. The family member II-5 was suggested to have noise-induced deafness.ConclusionIn this study, a novel missense mutation, c.5417C > A (p.A1806D), in MYH14 that led to postlingual nonsyndromic autosomal dominant SNHL were identified. The findings broadened the phenotype spectrum of MYH14 and highlighted the combined application of gene capture and Sanger sequencing is an efficient approach to screen pathogenic variants associated with genetic diseases.

Infantile Onset Encephalomyopathy, Heart Block, and Sensorineural Hearing Loss: RMND1-Associated Mitochondrial Disease

AbstractMutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mitochondrial disease and combined oxidation phosphorylation deficiency. This report describes a girl child of Indian origin with RMND1-associated mitochondrial disease. This 13-month-old girl, born to consanguineous parents presented with gradual loss of acquired milestones and recurrent vomiting from 5 months of age. She experienced failure to thrive, profound hypotonia, areflexia, and sensorineural deafness. Evaluation showed elevated serum lactate and complete heart block. Audiological evaluation done at 6 and 13 months of age revealed bilateral A type tympanogram, bilateral absent stapedial reflexes, absent otoacoustic emissions (OAE), and absent brainstem auditory evoked responses suggestive of bilateral profound sensorineural hearing loss. Muscle biopsy revealed evidence of ragged red fibers, ragged blue fibers, and Cytochrome coxidase (COX) deficient fibers on histochemistry and multiple complex deficiency on spectrophotometry. Exome sequencing revealed homozygous stop-loss variation, c.1349G &gt; C, in exon 12 of RMDN1 resulting in substitution of amino acid serine for stop codon at position 450 and subsequent elongation of the protein by 31 amino acids (p.Ter450SerextTer31) which was verified by Sanger's sequencing. This report further strengthens the phenotype genotype correlations in RMND1-associated mitochondrial disease, especially the occurrence of the reported variation in South Asian patients. In addition, familiarity with the phenotype might help the physician to do targeted metabolic testing and facilitate appropriate early interventions.

Petrosectomy in cochlear implant surgery

Introduction: Surgical treatment of deep heating loss with cochlear implant is well know and successful method which can be used both in children and adults. In patients with cholesteatoma or who underwent surgery canal wall down technique special surgical approach schooled be used – lateral/subtotal petrosectomy. Material and method: Patients witch deep bilateral sensorineural hearing loss and cholesteatoma of middle ear or after treatment of cholesteatoma with canal wall down mastoidectomy were included in the study. Retrospective analysis of patient’s data, radiological and audiological testing was performed. Results: In Department of otolaryngology for Children and Adults and Oncologic Laryngology Pomeranian University of Medicine between 2008 and 2018 90 surgeries of cochlear implantations were performed and among which 3 petrosectomies in one child (5years old) and two adults aged 62 and 73 years old who underwent canal wall down mastoidectomy in the past. In all patients single stage procedure was used, petrosectomy with cochlear implantation. Wound healing an postoperative period was uneventful in all cases. Follow up ranges from 26 to 32 months, in control computer tomography there is lack of indirect signs of recurrence of cholesteatoma. In a child, who accordingly is autistic and mentally retardated, good hearing result is observed and speech understanding, without spontaneous speech. In adult patients in free field audiometry hearing level is 35 and 40dB with speech understanding 80%. Discussion: Patients with chronic ear inflammation can be successfully and safely treated with cochlear implantation using petrosectomy technique. Subtotal/lateral petrosectomy is a method of choice when deep sensorineural hearing loss coexists with chronic inflammatory changes of the middle ear.

Three-year audiological outcomes of the latest generation middle ear transducer (MET) implant

PurposeTo evaluate the long-term audiological outcomes and safety of the latest generation of middle ear transducer (MET) among a group of Polish patients.MethodsTen patients aged 48–72 years with bilateral sensorineural hearing loss (n = 8) and mixed hearing loss (n = 2) were included in this study. Pure tone audiometry, sound thresholds, word recognition scores in quiet and speech reception thresholds in noise were assessed. Medical and technical complication information was gathered.ResultsAll the patients underwent unilateral implantation with the latest generation Cochlear MET between 2014 and 2016. Mean length of follow-up was 3.7 years. Compared to the unaided condition, the implant provided significant functional gain (mean M = 26.1 dB) at 12 months follow-up. Compared to before surgery, average word recognition in quiet at 65 dB and at 80 dB SPL, as well as speech reception threshold in noise, were significantly better at 12 months. However, postoperative air conduction thresholds 6 months after implantation worsened by 10.3 dB (standard deviation SD = 5.8 dB). Postoperatively, three patients had skin problems around the processor, and one of them completely resigned from using the device 5 months after activation. Technical failures occurred in 4 cases. There were 9 out of 10 patients who still used the MET, but only 5 of them used the processor regularly (every day).ConclusionDespite changes in the transducer implemented by the manufacturer, we observed a significant number of adverse events in users of the latest generation of MET.

A New Approach for Noise Suppression in Cochlear Implants: A Single-Channel Noise Reduction Algorithm.

The cochlea “translates” the in-air vibrational acoustic “language” into the spikes of neural “language” that are then transmitted to the brain for auditory understanding and/or perception. During this intracochlear “translation” process, high resolution in time–frequency–intensity domains guarantees the high quality of the input neural information for the brain, which is vital for our outstanding hearing abilities. However, cochlear implants (CIs) have coarse artificial coding and interfaces, and CI users experience more challenges in common acoustic environments than their normal-hearing (NH) peers. Noise from sound sources that a listener has no interest in may be neglected by NH listeners, but they may distract a CI user. We discuss the CI noise-suppression techniques and introduce noise management for a new implant system. The monaural signal-to-noise ratio estimation-based noise suppression algorithm “eVoice,” which is incorporated in the processors of Nurotron® EnduroTM, was evaluated in two speech perception experiments. The results show that speech intelligibility in stationary speech-shaped noise can be significantly improved with eVoice. Similar results have been observed in other CI devices with single-channel noise reduction techniques. Specifically, the mean speech reception threshold decrease in the present study was 2.2 dB. The Nurotron society already has more than 10,000 users, and eVoice is a start for noise management in the new system. Future steps on non-stationary-noise suppression, spatial-source separation, bilateral hearing, microphone configuration, and environment specification are warranted. The existing evidence, including our research, suggests that noise-suppression techniques should be applied in CI systems. The artificial hearing of CI listeners requires more advanced signal processing techniques to reduce brain effort and increase intelligibility in noisy settings.

Comparative effects of unilateral and bilateral bone conduction hearing devices on functional hearing and sound localization abilities in patients with bilateral microtia-atresia

Background: Various amplification options are available for patients with congenital bilateral conductive hearing loss. Unilateral bone conduction hearing device (BCHD) is widely used for these patients, whereas benefits of bilateral BCHDs in certain subgroups of patients require further exploration.Objectives: To evaluate functional and directional hearing in patients with unilateral Bonebridge (MEDEL) and contralateral ADHEAR (MEDEL) devices.Materials and methods: This study included 32 patients (20 males, 12 females), of mean age 11.8 years (range 7–27 years). Hearing thresholds, speech perception and sound localization were tested three months after activation of the Bonebridge under three conditions: unaided, unilateral BHCD (Bonebridge) and bilateral BHCDs (Bonebridge plus contralateral ADHEAR). Patient acceptance of these devices in daily life was evaluated by questionnaire.Results: Compared with unaided, the mean hearing thresholds (0.5, 1, 2, and 4 kHz) and speech perception with unilateral BCHD and bilateral BCHDs were improved significantly (p < .05 each). Markers of directional hearing ability, including percentages of accurate responses, bias angles and RMS errors, were significantly better with bilateral BCHDs than unilateral BHCD (p < .05 each). Questionnaire revealed high patient satisfaction with both unilateral and bilateral devices.Conclusions: Functional hearing and sound localization abilities were better with bilateral BCHDs than unilateral BCHD.

Bilateral congenital semicircular canal malformation and hearing loss - case report

The main aims of this observational study were to describe a poorly characterized malformation of the inner ear termed bilateral congenital semicircular canal malformation; determine if the degree and pattern of semicircular canal dysmorphology and the presence or absence of a well-formed cochlea predict audiological outcomes, type, and severity of congenital hearing loss; and investigate its relationship with known syndromic forms of hearing loss. Review of eight cases of hearing loss with radiographic evidence of congenital semicircular canal malformation was performed. Information was collected on clinical history, physical examination, computed tomography study and serial audiograms for all patients. Analyzed features included other syndrome-characteristic phenotypic dysmorphologies, audiometric configuration, severity and type of hearing loss, type of audiological rehabilitation, and presence of associated inner ear abnormalities besides those in the vestibular system. Among the eight cases included in the study, six patients had recognized syndromes/chromosomal abnormalities. Hearing loss was moderate to profound in all cases. All patients had bilateral semicircular canal deformities, with usually identical anatomical pattern on each side. Of the eight cases, six had normal cochlear development; malformations in the tympanic membrane and external auditory canal were only found in one; changes in ossicular chain were found in three patients; vestibules and vestibular aqueduct were normal in most cases; and abnormalities of oval window development and hypoplasia were found in two cases. The present study shows that a correlation between the severity and type of hearing loss and radiographic abnormalities is difficult to establish. Hearing loss associated with semicircular canal dysplasia is more likely due to anomalous membranous labyrinth development, which is not radiologically detectable by computerized tomography scan.

Biological age and rates of aging of patients with vibration disease and bilateral sensorineural hearing loss

Biological age and rates of aging of patients with vibration disease and bilateral sensorineural hearing loss were studied. The biological age of patients exceeded the calendar age by an average of 7.36±0.36 years and the proper biological age by 10.79±0.72 years. The rate of biological aging of the examined patients was 1.14±0.08 times higher than the rate of aging of their healthy peers.

Adaptive potential of the circulatory system in patients with vibration disease and sensorineural hearing loss

The study presents the results of the study of adaptive reactions and adaptive potential of the circulatory system of patients with vibration disease and chronic bilateral sensorineural hearing loss.

Abstract P3-11-02: Evaluation of patritumab/paclitaxel/trastuzumab over standard paclitaxel/trastuzumab in early stage, high-risk HER2 positive breast cancer: Results from the neoadjuvant I-SPY 2 trial

Abstract Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes to evaluate novel agents as neoadjuvant therapy for high-risk breast cancer. The primary endpoint is pathologic complete response (pCR) at surgery. The goal is to identify (graduate) regimens with ≥ 85% Bayesian predictive probability of success (i.e., demonstrating superiority to control) in a future 300-patient phase 3 1:1 randomized neoadjuvant trial with pCR endpoint within signatures defined by hormone-receptor (HR), HER2, and MammaPrint (MP) status. Regimens may leave the trial for futility (&amp;lt; 10% probability of success), maximum sample size accrual (with probability of success ≥ 10% and &amp;lt; 85%), or safety concerns as recommended by the independent DSMB. For HER2+ patients, the I-SPY2 control arm was 12 weekly cycles of paclitaxel+trastuzumab (TH, control) followed by doxorubicin/cyclophosphamide (AC) q2-3 weeks x4 and surgery. Patritumab is a fully human monoclonal antibody that inhibits HER3. In this experimental arm for HER2+ patients, patritumab was given q3w x 4 cycles (18mg/kg loading dose followed by 9mg/kg/dose) concurrent with paclitaxel and trastuzumab q1w x 12 weeks (PTH, treatment), followed by AC q2-3w. Methods: Women with tumors ≥ 2.5cm were eligible for screening. MP low/HR+ tumors were ineligible. MRI scans (baseline, 3 weeks after start of therapy, prior to AC, and prior to surgery) were used in a longitudinal statistical model to predict pCR for individual patients. Analysis was intention to treat. Patients who switched to non-protocol therapy count as non-pCR. Patients on treatment arm therapy at the time of arm closure are non-evaluable. Graduation potential was in 3 of 10 pre-defined signatures: all HER2+, HR-/HER2+, and HR+/HER2+. Results: The PTH regimen was stopped at the recommendation of the Safety Working Group and DSMB based on a safety event (bilateral sensorineural hearing loss, Gr 3) observed in one patient. At the time of arm closure, N=31 patients had received PTH treatment; 4 patients receiving PTH were changed to non-protocol therapy and removed from the analysis. The final estimated pCR report will consider 27 PTH and 31 TH as evaluable patients. Accrual was insufficient to assess graduation, however, there appears to be good signal in the HER2+HR- but not HER2+HR+ signatures. I-SPY 2 TRIAL Est. pCR at time of arm closureSignaturesPTH (Treatment)N= 31TH (Control)N = 31All (HER2+)0.40 (0.22 - 0.59), n=310.23 (0.09 - 0.37), n=31HR-/HER2+0.64 (0.36 - 0.91), n=110.30 (0.12 - 0.47), n=12HR+/HER2+0.28 (0.08 - 0.48), n=200.20 (0.06 - 0.34), n=19 HR+/HER2+0.28 (0.08 - 0.48), n=200.20 (0.06 - 0.34), n=19The patient who developed Gr3 sensorineural hearing loss 6 days after the 2nd patritumab (and 4th paclitaxel/trastuzumab) treatment, did not recover her hearing after patritumab was stopped, and also reported Gr3 vulvovaginal pain, vulvitis, and vaginal inflammation. Other gynecological symptoms in the PTH arm include: 1 pt with Gr1 vaginal hemorrhage, and 1 pt with Gr2 dyspareunia. There was a higher frequency of Gr3 hypokalaemia (12.5% vs. 3.2%). One pt in the PTH arm reported Gr3 small intestinal obstruction which resolved with conservative management. Conclusion: The I-SPY 2 study aims to assess the probability that investigational regimens will be successful in a phase 3 neoadjuvant trial; PTH was stopped due to safety concerns, although there was activity in the HER2+ HR- signature. This is the first report of Gr3 hearing loss associated with patritumab/paclitaxel/trastuzumab, and thus attribution is uncertain. Citation Format: Teresa L Helsten, Shelly S Lo, Christina Yau, Kevin Kalinsky, Anthony D Elias, Anne M Wallace, A. Jo Chien, Janice Lu, Julie E Lang, Kathy S Albain, Erica Stringer-Reasor, Amy S Clark, Judy C Boughey, Erin D Ellis, Douglas Yee, Angela DeMichele, Claudine Isaacs, Jane Perlmutter, Hope S Rugo, Richard Schwab, Nola M. Hylton, W. Fraser Symmans, Michelle E Melisko, Laura J van't Veer, Amy Wilson, Ruby Singhrao, Smita M Asare, Ashish Sanil, Donald A Berry, Laura J Esserman. Evaluation of patritumab/paclitaxel/trastuzumab over standard paclitaxel/trastuzumab in early stage, high-risk HER2 positive breast cancer: Results from the neoadjuvant I-SPY 2 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-02.

Aetiology and Hearing Status of Children under 12 years in a School for Hearing Impaired

Objective: To assess degree, type and cause of hearing loss in children under 12 years of age in preschool for hearing impaired children.&#x0D; Methods: This cross sectional study was carried out in children of integrated preschool for hearing impaired children (IPSHIC) of SAHIC, Mohakhali, Dhaka, from September 2010 to March 2011. 50 deaf children were included with age 3-12 years and clinically detected hearing impairment. Data were collected by detailed history, clinical examination and audiometric findings and result were expressed in table form.&#x0D; Results: Most of the children presented with bilateral profound hearing loss and majority of patients presented with sensorineural type of hearing loss. Family history positive in 36% cases and consanguineous marriage were found in 34%.Commonest causes of deafness was infection.&#x0D; Conclusion: Early detection with universal neonatal screening should be practiced in our country and early rehabilitation reveals better out come.&#x0D; Bangladesh J Otorhinolaryngol; April 2016; 22(1): 36-39