The vibrating ossicular prosthesis in children and adolescents: a retrospective study.

PURPOSE: The primary objective of the retrospective study was to collect speech intelligibility data on children and adolescents implanted with the vibrating ossicular prosthesis (VORP) 503. METHODS: This was a retrospective, multicentre study on 55 children and adolescents from 6 German clinics aged between 5 and 17 years suffering from mixed or conductive hearing loss implanted with a VORP 503. Pre- and postoperative bone-conduction pure tone thresholds were measured at 0.5, 1, 2 and 4 kHz, and word recognition scores in the unaided and VORP 503-aided conditions using monosyllabic speech intelligibility tests measured at 65-dB sound pressure level (SPL) were determined. RESULTS: Mean pre- and postoperative bone-conduction thresholds remained unchanged, showing the preservation of inner ear hearing. Speech intelligibility assessed in quiet at 65-dB SPL improved on average from 24.5% (SD ± 25.4) unaided to 86.4% (SD ± 13.4) aided. The average improvement of 61.9% (SD ± 25.3) was clinically and statistically significant. A total of three complications were found in the medical records of 55 subjects. The responsible investigators judged these events as procedure related. CONCLUSION: The treatment of children suffering from conductive or mixed hearing loss with the VORP 503 implant demonstrates excellent aided benefit in terms of speech understanding and only minor complications.

Systematic review to evaluate the safety, efficacy and economical outcomes of the Vibrant Soundbridge for the treatment of sensorineural hearing loss.

Introduced in the late 90s, the active middle ear implant Vibrant Soundbridge (VSB) is nowadays used for hearing rehabilitation in patients with mild to severe sensorineural hearing loss (SNHL) unable to tolerate conventional hearing aids. In experienced hands, the surgical implantation is fast done, safe and highly standardized. Here, we present a systematic review, after more than 15 years of application, to determine the efficacy/effectiveness and cost-effectiveness, as well as patient satisfaction with the VSB active middle ear implant in the treatment of mild to severe SNHL. A systematic search of electronic databases, investigating the safety and effectiveness of the VSB in SNHL plus medical condition resulted in a total of 1640 papers. After removing duplicates, unrelated articles, screening against inclusion criteria and after in-depth screening, the number decreased to 37 articles. 13 articles were further excluded due to insufficient outcome data. 24 studies remained to be systematically reviewed. Data was searched on safety, efficacy and economical outcomes with the VSB. Safety-oriented outcomes included complication/adverse event rates, damage to the middle/inner ear, revision surgery/explant rate/device failure and mortality. Efficacy outcomes were divided into audiological outcomes, including hearing thresholds, functional gain, speech perception in quiet and noise, speech recognition thresholds, real ear insertion gain and subjective outcomes determined by questionnaires and patient-oriented scales. Data related to quality of life (QALY, ICER) were considered under economical outcomes. The VSB turns out to be a highly reliable and a safe device which significantly improves perception of speech in noisy situations with a high sound quality. In addition, the subjective benefit of the VSB was found to be mostly significant in all studies. Finally, implantation with the VSB proved to be a cost-effective and justified health care intervention.

A genetic basis for mechanosensory traits in humans.

In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

Patient selection for upper airway stimulation: is concentric collapse in sleep endoscopy predictable?

PURPOSE: Upper airway stimulation is an effective treatment option for obstructive sleep apnea after failure of positive airway pressure (PAP) therapy. To ensure a therapeutic effect, closed-loop hypoglossal nerve implants require the absence of palatal complete concentric collapse during sleep endoscopy. The frequency and potential predictors of this exclusion criterion are unknown. METHODS: Over a 2-year period, 74 consecutive patients with sleep apnea who sought PAP alternatives were evaluated with sleep endoscopy using propofol. The influence of sleep apnea severity and anthropometric characteristics as predictors of sleep endoscopy results was investigated. RESULTS: One-fifth of all patients showed a concentric collapse. Gender and age did not predict the presence of concentric collapse, but higher body mass and apnea hypopnea index values were predictive (p = 0.011; e.g., 0.026). The most commonly used body mass index values for upper airway stimulation indications demonstrated acceptable specificity (BMI 32 kg/m(2) 0.71, 95 % confidence interval = 0.57, 0.82; e.g., 35 kg/m(2) 0.81, 95 % confidence interval = 0.69, 0.90). Despite the association with overweight, a significant number of severely overweight patients had no concentric palatal collapse. CONCLUSIONS: Concentric collapse is a somewhat common condition encountered in sleep endoscopy evaluations of PAP alternatives, and cannot be sustainably predicted with anthropometric or sleep assessments. Sleep surgeons should be aware of the possibility of concentric collapse, especially in candidates who are more overweight and have severe sleep apnea. Sleep endoscopy can be useful for providing information about continuous positive airway pressure (CPAP) alternatives or to motivate patient adherence to treatment.

The Rib Cartilage Concept in Microtia.

There is a long history of rib cartilage use in reconstruction for microtia. This article aims to describe the modern techniques of autologous auricular reconstruction in detail, to elucidate the modifications for certain anatomical or disease-related conditions, and to contrast the different strategies used by other surgeons. The two mainstays of successful reconstruction with excellent results are the fabrication of the framework and soft tissue management. A three-dimensional framework mimics the curves, indentations, and peaks of a normal ear with maximal stability. Recently, the creation of a conchal bowl and an additional tragal strut has become a standard procedure. Soft tissue management is highly specific to each patient and equally contributes to the final result of the procedure. The correct position of the incision line and the trimming of the local flaps require thorough planning. Most of the individual modifications must be made in soft tissue management, particularly in patients with a low hairline and facial asymmetry. Autologous auricular reconstruction is a standard procedure that needs to be individualized to each patient. However, it is challenging and requires intensive training. In experienced hands, patients experience excellent results.

Trauma Management of the Auricle.

Smaller injuries of the auricle, such as lacerations without tissue loss, have more or less standardized treatment protocols that require thorough wound closure of each affected layer. Even extended lacerations of larger parts of the ear quite often heal with only minor irregularities. New in vivo diagnostic tools have aided the understanding of this outstanding "skin flap behavior." At the other end of the trauma severity spectrum are partial or complete amputations of the ear. Here, the debate has become more intense over the last decade. There were numerous reports of successful microvascular reattachments in the 1990s. Consequently, pocket methods and their variations have received increasing attention because the results seem to be convincing. Nevertheless, the pressure damage due to banking larger parts of the elastic cartilage in the mastoid region is tremendous, and the tissue for secondary reconstruction is severely injured. Particularly in cases of acute trauma with relevant concomitant injuries to the patient and in cases in which the amputated area is in a critical state, direct wound closure is a straightforward and safe option. Subsequent thoughtfully planned secondary reconstruction using ear or rib cartilage, or even allogenous material as an ear framework, can achieve excellent aesthetic results.

Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development.

Somatic sensation relies on the transduction of physical stimuli into electrical signals by sensory neurons of the dorsal root ganglia. Little is known about how and when during development different types of sensory neurons acquire transduction competence. We directly investigated the emergence of electrical excitability and mechanosensitivity of embryonic and postnatal mouse sensory neurons. We show that sensory neurons acquire mechanotransduction competence coincident with peripheral target innervation. Mechanotransduction competence arises in different sensory lineages in waves, coordinated by distinct developmental mechanisms. Sensory neurons that are mechanoreceptors or proprioceptors acquire mature mechanotransduction indistinguishable from the adult already at E13. This process is independent of neurotrophin-3 and may be driven by a genetic program. In contrast, most nociceptive (pain sensing) sensory neurons acquire mechanosensitive competence as a result of exposure to target-derived nerve growth factor. The highly regulated process of mechanosensory acquisition unveiled here, reveals new strategies to identify molecules required for sensory neuron mechanotransduction.

Grading system for the selection of patients with congenital aural atresia for active middle ear implants.

INTRODUCTION: Active middle ear implants (aMEI) are being increasingly used for hearing restoration in congenital aural atresia. The existing gradings used for CT findings do not meet the requirements for these implants. Some items are expendable, whereas other important imaging factors are missing. We aimed to create a new grading system that could describe the extent of the malformation and predict the viability and challenges of implanting an aMEI. METHODS: One hundred three malformed ears were evaluated using HRCT of the temporal bone. The qualitative items middle ear and mastoid pneumatization, oval window, stapes, round window, tegmen mastoideum displacement and facial nerve displacement were included. An anterior- and posterior round window corridor, oval window and stapes corridor were quantified and novelly included. They describe the size of the surgical field and the sight towards the windows. RESULTS: The ears were graded on a 16-point scale (16-13 easy, 12-9 moderate, 8-5 difficult, 4-0 high risk). The strength of agreement between the calculated score and the performed implantations was good. The comparison of the new 16-point scale with the Jahrsdoerfer score showed that both were able to conclusively detect the high-risk group; however, the new 16-point scale was able to further determine which malformed ears were favorable for aMEI, which the Jahrsdoerfer score could not do. CONCLUSION: The Active Middle Ear Implant Score for aural atresia (aMEI score) allows more precise risk stratification and decision making regarding the implantation. The use of operative corridors seems to have significantly better prognostic accuracy than the Jahrsdoerfer score.

Influence of silicone gel on standardized postoperative scars.

BACKGROUND: Silicone gel is one therapeutic approach in the treatment and prevention of excessive scarring. The likely mechanism of action is the hydration of the tissue. This should lead to reduced angiogenesis and capillary blood flow. The efficacy is still controversial and the evidence base, insufficient. The aim of this prospective and standardized study is to investigate silicone gel in the preventive treatment of scars. PATIENTS AND METHODS: Included in the study were 20 patients with costal cartilage harvest. Half of a standard chest scar was treated for three months with a silicone gel. The other half served as an internal control. After three months both scar sides were compared subjectively by visual analog scale and objectively by elasticity, moisture and color measurements. RESULTS: Of 19 patients 8 had a better subjective result in the treated half. In one subject, no difference was seen. A worse subjective result in the treated half was seen in 10 out of 19. The objective measurements showed no significant difference. A correlation between the different results was not seen. CONCLUSIONS: The use of silicone gel caused subjective differences within the same scar (worsening as well as improvement of the appearance). Positive effects were not detectable in the investigated parameters.

Multicenter Results With an Active Transcutaneous Bone Conduction Implant in Patients With Single-sided Deafness.

OBJECTIVE: To evaluate the audiological and subjective benefit from hearing rehabilitation with an active bone conduction implant in subjects with single-sided sensorineural deafness (SSD). STUDY DESIGN: Prospective, multicenter, single-subject repeated measures. SETTING: Tertiary referral center, five clinics in Germany and Switzerland. PATIENTS: Seventeen subjects aged 18 years and older with severe to profound unilateral sensorineural hearing loss and contralateral normal hearing were followed up for 24 months. INTERVENTION: Active bone conduction implant. MAIN OUTCOME MEASURES: Speech understanding in noise was assessed in three situations: with signal from front, deaf, or normal hearing side (with noise from front in all set-ups). Subjective benefit was evaluated using the Speech, Spatial, and Qualities of Hearing (SSQ-B) and Bern Benefit in Single-Sided Deafness (BBSS) questionnaire. RESULTS: When the signal was coming from the deaf side the mean improvement of the speech reception threshold in noise ranged from 1.5 up to 2.2 dB with the device and was statistically and clinically significant at all tested timepoints. No significant difference between the aided and unaided situation was found when signal and noise were coming from the front. With the signal from the normal hearing side no clinically significant difference, that is, greater than 1 dB between the aided and unaided situation was found. The SSQ-B and BBSS questionnaire showed an overall improvement with no significant difference between time points. CONCLUSIONS: The study demonstrates long-term efficacy and benefit of the device in adults with SSD. Patients reported substantial and persistent subjective benefit from the active bone conduction implant.

A Transcutaneous Active Middle Ear Implant (AMEI) in Children and Adolescents: Long-term, Multicenter Results.

OBJECTIVE: Evaluation of the long-term safety and performance of an active middle ear implant (AMEI) in the treatment of hearing loss in children and adolescents with a primary focus on improvement in speech discrimination. STUDY DESIGN: Prospective, multicentric, single-subject repeated-measures design in which each subject serves as his or her own control. SUBJECTS: Thirty-one pediatric subjects aged 5 to 17 years. INTERVENTION: Implantation of an active middle ear implant. METHODS: Improvement in word recognition scores, speech reception thresholds (SRT) in quiet and noise, in addition to air conduction, bone conduction, and sound field thresholds were evaluated in two age groups. RESULTS: Residual hearing did not change over time and speech intelligibility significantly improved and remained stable after 36 months. Children aged 5 to 9 improved in WRS from 21.92 to 95.38% and in SRT in quiet and in noise respectively from 62.45 dB SPL (sound pressure level) and +1.14 dB SNR to 42.07 dB SPL and -4.45 dB SNR. Adolescents aged 10 to 17 improved in WRS from 12.78 to 84.71% and in SRT in quiet and in noise respectively from 63.96 dB SPL and +3.32 dB SNR to 35.31 dB SPL and -4.55 dB SNR. CONCLUSIONS: The AMEI, under investigation, is a safe treatment for children and adolescents, and significantly improved audiological performance that remains stable on the long-term scale (up to 36 mo postimplantation). In general, all adult-related issues and questions regarding safety and performance can also be applied to the pediatric population, as no apparent specific issues developed.

International Consensus Recommendations on Microtia, Aural Atresia and Functional Ear Reconstruction.

The aim of this report is to provide international recommendations for functional ear reconstruction in patients with microtia and aural atresia. All patients with microtia and external auditory atresia should be seen in the setting of a multidisciplinary team and agreed treatment outcomes should be measured, so that techniques, approaches, and results can be compared. The methods are expert opinion from the members of the International Microtia and Atresia Workgroup (IMAW). The consensus recommendations reported herein take into account the variability in practice patterns present among experts in the field; the degree of consensus was quantified by presenting the percentage of above authors who agree or partially agree with each statement. Recommendations include the definition and classification of microtia/atresia, treatment of microtia, treatment of congenital aural atresia, flowchart of functional ear reconstruction, and future research directions. Patients with microtia and aural atresia can be guided by the consensus recommendations provided herein.

Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer.

Protein expression of human toll-like receptors (TLR) 1-10 was measured in cell lines and solid tumors of head and neck squamous cell carcinoma (HNSCC). All HNSCC cell lines and 80% of solid tumors were found to express TLR3 as a predominantly intracellular protein, while no other TLR proteins were expressed. TLR3 has previously been shown to contribute to the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor which promotes several types of human cancers. Significantly, NF-kappaB expression was strongest in protein extracts from carcinoma tissue in which TLR3 was overexpressed. Inhibition of TLR3 expression in permanent HNSCC cell lines resulted in decreased expression of the oncoprotein c-Myc resulting in decreased cell proliferation. Correspondingly, overexpression of human TLR3 in mouse fibroblasts resulted in an upregulation of c-Myc and increased sensitivity for PolyI:C-induced cell proliferation. Our data suggest that TLR3 contributes to the malignant phenotype leading to invasive carcinoma in HNSCC.

The psychosocial consequences of reconstruction of severe ear defects or third-degree microtia with rib cartilage.

BACKGROUND: There are few data focusing on the improvement of psychosocial functioning and self-esteem in patients with congenital or acquired severe auricular defects. OBJECTIVE: We investigated the satisfaction of patients following auricular reconstruction with rib cartilage. METHODS: One hundred patients treated for reconstruction with rib cartilage for congenital or traumatic auricular defects have been evaluated retrospectively for changes in self-esteem, performance ability, and psychosocial attitude using a clinically established questionnaire, Frankfurter Selbstkonzeptskalen (FSKN). In addition, patients were asked to judge the new auricle and the thoracic scar using a new questionnaire. RESULTS: Of 68 patients who took part in this study, almost 90% could integrate the new ear into their body concept. If faced with the same decision for surgery again, 75% would again choose a reconstruction with rib cartilage. More than three-quarters rated the thoracic scar as acceptable in relation to the benefits of the new ear, although one-third felt uncomfortable with the pain and cosmetic appearance of the thoracic scar. According to the results of the FSKN questionnaire, values in psychosocial abilities improved postoperatively. There was no clear change in either self-esteem or performance ability. CONCLUSIONS: Ear reconstruction with rib cartilage remains, under most circumstances, the procedure of choice for repairing auricular defects. There is a high acceptance of this method among patients, although the impact of the thoracic scar needs to be discussed extensively before surgery. The importance of the surgeon's experience cannot be underestimated, because it determines the aesthetic results and the patient's satisfaction in this challenging area of plastic surgery.

Hearing Rehabilitation in Congenital Middle Ear Malformation.

Microtia and atresia cause significant conductive hearing loss of up to 60 dB HL. The bilateral cases suffer from severely restricted communication abilities and require immediate acoustic stimulation. There is also growing evidence that unilateral cases benefit from an early and selective stimulation of the affected side. Hearing restoration can be performed in selected cases of minor malformation by classic middle ear reconstruction. However, the majority of patients presumably benefit better from a hearing aid. There are 3 main types: active middle ear implants, active bone conduction implants and passive bone conduction implants. All implants improve speech perception, speech recognition, the signal-to-noise ratio and directional hearing. The extent varies among implants and requires further studies. Decision making on the implant type depends on the extent of malformation and hence the preoperative imaging. New scoring systems provide reliable risk stratification. Second it depends on the age of the patient. The active middle ear implants provide a selective stimulation of the affected side and are beneficial if implanted in the first years of life during the maturation period of the auditory system. In conclusion, hearing rehabilitation of congenital atresia should be performed as early as possible. This includes not only the bilateral but also the unilateral affected patients.

Decreased migration of myeloid dendritic cells through increased levels of C-reactive protein.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), a variety of immunomodulatory mediators contribute to strongly impaired immune functions. The secretion of C-reactive protein (CRP) by HNSCC cells and its influence on human myeloid dendritic cells (MDC) was investigated. MATERIALS AND METHODS: The CRP levels were analyzed using photometric methods and real-time PCR. The MDC were isolated from peripheral blood by 'magnetic bead separation' and incubated with different CRP concentrations. The CRP isoforms were analyzed by native PAGE (polyacrylamide gel electrophoresis). The cells were analyzed using migration assays and flow cytometry. RESULTS: HNSCC cell lines were able to autonomously express C-reactive protein. Pentameric CRP triggered the down-regulation of chemokine receptor CCR5 and led to a decreased migration of human MDC. CONCLUSION: CRP appeared to be a modulator of the migration activity of human MDC. The functional modulation of immune cells represents a crucial immune escape mechanism of human carcinomas.

Functional alteration of myeloid dendritic cells through head and neck cancer.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), the secretion of various immunosuppressive mediators contributes to large-scale effects on the immune functions. The influence of HNSCC on various cellular functions of human myeloid dendritic cells (MDC) was analyzed in this work. MATERIALS AND METHODS: MDCs were isolated from peripheral blood by 'magnetic bead separation'. Cellular functions were analyzed using flow cytometry, migration- and ELISPOT assays as well as cytokine detection assays. RESULTS: HNSCC massively affects MDCs to induce effective T-cell responses. Analysis of MDC migration and cytokine secretion revealed that HNSCC triggers the production of tumor-promoting and immunosuppressive cytokines IL-1 and IL-10 and results in an increased MDC migration activity. CpG-ODN is able to act contradictory to HNSCC. CONCLUSION: HNSCC is able to modulate various functions of human MDCs. CpG-ODN is suggested as a potential immunostimulatory agent of human MDC.

Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features.

Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid.

1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clamp and calcium-imaging techniques, we show that extracellular application of 20 microM ACA completely blocked ADPR-induced whole-cell currents and H2O2-induced Ca2+ signals (IC50 = 1.7 microM) in HEK293 cells transfected with human TRPM2. Two other PLA2 inhibitors, p-bromophenacyl bromide (BPB; 100 microM) and arachidonyl trifluoromethyl ketone (20 microM), had no significant effect on ADPR-stimulated TRPM2 activity. 3. Inhibition of TRPM2 whole-cell currents by ACA was voltage independent and accelerated at decreased pH. ACA was ineffective when applied intracellularly. The single-channel conductance was not changed during ACA treatment, suggesting a reduction of TRPM2 open probability by modulating channel gating. 4. ACA (20 microM) also blocked currents through human TRPM8 and TRPC6 expressed in HEK293 cells, while BPB (100 microM) was ineffective. TRPC6-mediated currents (IC50 = 2.3 microM) and TRPM8-induced Ca2+ signals (IC50 = 3.9 microM) were blocked in a concentration-dependent manner. 5. ADPR-induced currents in human U937 cells, endogeneously expressing TRPM2 protein, were fully suppressed by 20 microM ACA. 6. Our data indicate that ACA modulates the activity of different TRP channels independent of PLA2 inhibition. Owing to its high potency and efficacy ACA can serve, in combination with other blockers, as a useful tool for studying the unknown function of TRPM2 in native cells.