Wilko Grolman

The effectiveness of bilateral cochlear implants for severe-to-profound deafness in children: a systematic review.

Objective: To assess the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation alone or with a contralateral hearing aid (bimodal stimulation), in children with severe-to-profound hearing loss. Recently, the National Institute for Health and Clinical Excellence (NICE) in the U.K. has conducted a systematic review on cochlear implantation. We decided to update the pediatric part of the NICE review. Data Sources: The electronic databases MEDLINE and Embase were searched for European, North American, and Australasian studies published between October 2006 and June 2009. Reference lists of the included articles were also searched for relevant articles. Study Selection: Studies were included if they comprised data on comparisons between bilateral cochlear implantation and unilateral cochlear implantation and/or bilateral cochlear implantation and bimodal stimulation, in children with severe-to-profound sensorineural hearing loss. The following outcome measures were analyzed: audiological, speech perception, speech production, functional capacities, health-related quality of life, and/or educational outcomes. Data Extraction: Characteristics of the participants, interventions, outcomes, and methodological comments were entered into data extraction forms and the level of evidence was assessed. Data Synthesis: Results were standardized for each outcome measure by calculating a standardized mean difference (effect size). Conclusion: Effect sizes could not be pooled because of the heterogeneity of the studies. Therefore, we presented the results qualitatively. Although the level of evidence was low, the advantages of bilateral cochlear implants corresponded with the primary benefits of bilateral hearing, that is, improved speech perception in quiet and noise. Localization results were less consistent. No data on audiologic, speech production, or educational outcomes were available.

Neurotrophins and their role in the cochlea

Spiral ganglion cell (SGC) degeneration following hair cell loss can be prevented by administration of exogenous neurotrophic factors. Many of these neurotrophic factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been described to be involved in the development of the rodent cochlea. While expression of most of the neurotrophins has decreased to below detectable levels during adulthood (only NT-3 remains highly expressed), their respective receptors remain present in SGCs. Indeed much less is known about the function of neurotrophins in the mature cochlea. Such knowledge is crucial in the search for tools to improve SGC survival following cochlear implantation. In this review, we will critically regard the current experimental findings of neurotrophic treatment of the SGCs in the perspective of fundamental cellular mechanisms underlying neurotrophin signaling. We conclude that, in order to fully apprehend the effects of neurotrophic treatment of degenerating SGCs and in order to consider clinical application of neurotrophins, future research should focus (a) on characterizing the expression pattern of neurotrophins in the cochlea after deafening, (b) on more detailed characterization of functional and morphological changes of SGCs associated with both deafening and neurotrophic treatment and (c) on the possible self-supporting state of SGCs after cessation of short-term neurotrophic treatment.

Diffusion-weighted MR Imaging in Laryngeal and Hypopharyngeal Carcinoma: Association between Apparent Diffusion Coefficient and Histologic Findings

PURPOSE To investigate the relationship between the histologic characteristics of head and neck squamous cell carcinoma and apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS The institutional ethics committee approved this study and waived informed consent. In head and neck squamous cell carcinoma, local failure after chemotherapy and/or radiation therapy correlates with pretreatment ADC. However, the histopathologic basis of this correlation remains unclear. In this study, 16 patients with head and neck squamous cell carcinoma were enrolled (median age, 60 years; range, 49-78 years). Before undergoing total laryngectomy, patients underwent 1.5-T diffusion-weighted MR imaging. After resection, whole-mount hematoxylin-eosin-stained sections were registered to the MR images. Cellular density; nuclear, cytoplasmic, and stromal area; and nuclear-cytoplasmic ratio within the tumor were calculated by using image-based segmentation on four consecutive slices. Mean ADC of the corresponding tumor region was calculated. Spearman correlations between ADC and histologic characteristics were calculated. RESULTS ADC was significantly and inversely correlated with cell density (n = 16, r = -0.57, P = .02), nuclear area (n = 12, r = -0.64, P = .03), and nuclear-cytoplasmic ratio (n = 12, r = -0.77, P ≤ .01). ADC was significantly and positively correlated with percentage area of stroma (n = 12, r = 0.69, P = .01). Additionally, the percentage area of stroma was strongly interdependent with the percentage area of nuclei (n = 12, r = -0.97, P ≤ .01). CONCLUSION ADC was significantly correlated with cellularity, stromal component, and nuclear-cytoplasmic ratio. The positive correlation of ADC and stromal component suggests that the poor prognostic value of high pretreatment ADC might partly be attributed to the tumor-stroma component, a known predictor of local failure.

Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: A systematic review

Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV). HPV-positive OPSCC is considered a distinct molecular entity with a better prognosis than HPV-negative cases of OPSCC. However, the exact pathogenic mechanisms underlying the differences in clinical and molecular behavior between HPV-positive and HPV-negative OPSCC remain poorly understood. Epigenetic events play an important role in the development of cancer. Hypermethylation of DNA in promoter regions and global hypomethylation are 2 epigenetic changes that have been frequently observed in human cancers. It is suggested that heterogeneous epigenetic changes play a role in the clinical and biological differences between HPV-positive and HPV-negative tumors. Unraveling the differences in methylation profiles of HPV-associated OPSCC may provide for promising clinical applications and may pave the road for personalized cancer treatment. This systematic review aims to assess the current state of knowledge regarding differences in promoter hypermethylation and global methylation between HPV-positive and HPV-negative OPSCC.

Measuring disease-specific health-related quality of life to evaluate treatment outcomes in tinnitus patients: a systematic review.

OBJECTIVE: To identify all disease-specific health-related quality-of-life (HR-QoL) instruments used to assess tinnitus in clinical trials and detail their psychometric properties. DATA SOURCES: A literature search was performed in the bibliographical databases of PubMed and Embase to identify all articles using specific HR-QoL instruments in tinnitus trials. REVIEW METHODS: The HR-QoL instruments used in these articles were investigated in more detail, focusing on characteristics and psychometric values by two independent reviewers. RESULTS: Seventeen studies were identified by the systematic search. The most used HR-QoL questionnaire was the Tinnitus Questionnaire, followed by the Tinnitus Handicap Inventory, the Tinnitus Reaction Questionnaire, and the Tinnitus Handicap Questionnaire. Internal consistency (Cronbachs α > 0.9) and reproducibility (> 0.8) were high for all questionnaires, and there was heterogeneity in responses between patients, endorsing the use of these questionnaires for discriminative purposes. However, the responsiveness, i.e., the usefulness of these questionnaires in evaluating treatment effects, is not known yet. CONCLUSION: The HR-QoL instruments used in tinnitus trials appear not to be validated to measure effectiveness of interventions. Using tests or instruments that are valid and reliable is a crucial component of research quality, and both should therefore be studied before final conclusions can be drawn from the questionnaires in upcoming clinical trials.

Cochlear Implantation for Patients With Single-Sided Deafness or Asymmetrical Hearing Loss: A Systematic Review of the Evidence

Objective A systematic review of the literature to evaluate the clinical outcome of cochlear implantation for patients with single-sided deafness (SSD) or asymmetrical hearing loss (AHL). Data Sources We searched the PubMed, Embase, Cochrane Library, and CINAHL databases from their inception up to December 10, 2013 for SSD or AHL and cochlear implantation or their synonyms. Study Selection In total, 781 articles were retrieved, of which 15 satisfied the eligibility criteria. Our outcomes of interest were speech perception in noise, sound localization, quality of life (QoL), and tinnitus. Data Extraction Critical appraisal showed that six studies reported on less than five patients or that they carried a low directness of evidence or a high risk of bias. Therefore, we extracted the data of nine studies (n = 112). Patient numbers, age, duration of deafness, classification of deafness, pure tone audiometry, follow-up duration, and outcome measurements were extracted from all nine articles. Data Synthesis Because of large heterogeneity between studies, we were not able to pool data in a meta-analysis. We therefore summarized the results of the studies specified per outcome. Conclusion There are no high-level-of-evidence studies concerning cochlear implantation in patients with SSD or AHL. Current literature suggests important benefits of cochlear implantation regarding sound localization, QoL, and tinnitus. Varying results were reported for speech perception in noise, possibly caused by the large clinical heterogeneity between studies. Larger and high-quality studies are certainly warranted.

High incidence of gastropharyngeal and gastroesophageal reflux after total laryngectomy

Gastroesophageal reflux (GER) appears to be related to laryngeal carcinoma. Little is known about GER and gastropharyngeal reflux (GPR) in the laryngectomized patient. Therefore, GER and GPR were studied in laryngectomized patients.

Auditory-Nerve Responses to Varied Inter-Phase Gap and Phase Duration of the Electric Pulse Stimulus as Predictors for Neuronal Degeneration

After severe hair cell loss, secondary degeneration of spiral ganglion cells (SGCs) is observed—a gradual process that spans years in humans but only takes weeks in guinea pigs. Being the target for cochlear implants (CIs), the physiological state of the SGCs is important for the effectiveness of a CI. For assessment of the nerve’s state, focus has generally been on its response threshold. Our goal was to add a more detailed characterization of SGC functionality. To this end, the electrically evoked compound action potential (eCAP) was recorded in normal-hearing guinea pigs and guinea pigs that were deafened 2 or 6 weeks prior to the experiments. We evaluated changes in eCAP characteristics when the phase duration (PD) and inter-phase gap (IPG) of a biphasic current pulse were varied. We correlated the magnitude of these changes to quantified histological measures of neurodegeneration (SGC packing density and SGC size). The maximum eCAP amplitude, derived from the input–output function, decreased after deafening, and increased with both PD and IPG. The eCAP threshold did not change after deafening, and decreased with increasing PD and IPG. The dynamic range was wider for the 6-weeks-deaf animals than for the other two groups. Excitability increased with IPG (steeper slope of the input–output function and lower stimulation level at the half-maximum eCAP amplitude), but to a lesser extent for the deafened animals than for normal-hearing controls. The latency was shorter for the 6-weeks-deaf animals than for the other two groups. For several of these eCAP characteristics, the effect size of IPG correlated well with histological measures of degeneration, whereas effect size of PD did not. These correlations depend on the use of high current levels, which could limit clinical application. Nevertheless, their potential of these correlations towards assessment of the condition of the auditory nerve may be of great benefit to clinical diagnostics and prognosis in cochlear implant recipients.

Ocular Vestibular Evoked Myogenic Potentials: Frequency Tuning to Air-Conducted Acoustic Stimuli in Healthy Subjects and Ménière’s Disease

Ocular vestibular evoked myogenic potentials (oVEMP) in response to 250-, 500- and 1000-Hz air-conducted short tone bursts were studied in 22 healthy subjects and 37 Ménière’s disease patients. The goal of this study was to investigate normal tuning characteristics of the oVEMP and the possible oVEMP changes with respect to frequency dependence in Ménière’s disease. In unilateral Ménière’s disease patients, a distinction was made between affected ears and unaffected ears. It was found that in normal subjects, the oVEMP tunes to a stimulus frequency of 500 Hz, with the highest amplitude and lowest threshold at this particular frequency. Generally, Ménière’s disease patients showed lower amplitudes and higher thresholds than normal subjects at all 3 stimulus frequencies in both the affected and the unaffected ear. Additionally, for ears affected by Ménière’s disease, the best stimulus frequency was 1000 Hz. With the use of this altered tuning for these ears, we tried to find a criterion for distinguishing normal from Ménière’s disease ears.

Spread of Excitation Measurements for the Detection of Electrode Array Foldovers: A Prospective Study Comparing 3-Dimensional Rotational X-ray and Intraoperative Spread of Excitation Measurements

Objective: The optimal positioning of electrode arrays in the cochlea is extremely important. Our standard approach is to use a 3-dimensional rotational x-ray for the intraoperative determination of the position of the electrode array. We wanted to see if spread of excitation (SOE) is useful for determining the electrode array position within the cochlea. Study Design: Prospective blind study design. Setting: Tertiary University Referral Center (Cochlear Implantation Center Amsterdam-Academic Medical Center, University of Amsterdam). Patients: Seventy-two implanted ears with a Cochlear Freedom device. Intervention: After cochlear implantation, we compared the 3-dimensional rotational x-ray imaging and SOE measurements. The investigators were blinded for the intraoperative surgeon findings and also for the imaging findings. Outcome Measure(s): Electrode array foldovers within the cochlea and the reliability of the SOE measurements. Results: We placed implants in 72 ears in this study, and all procedures seemed to be surgically uneventful. To our surprise, we discovered 4 electrode foldovers in this group. Of the 4 foldovers, 3 were corrected intraoperatively. Conclusion: We found that intraoperative imaging and/or electrophysiologic measurements such as the SOE provide very useful information regarding electrode position within the cochlea. Spread of excitation is effective in detecting electrode array foldovers if the audiologist is experienced. Some software modifications are suggested.