Differing Bilateral Benefits for Spatial Release From Masking and Sound Localization Accuracy Using Bone Conduction Devices.

OBJECTIVES: Normal binaural hearing facilitates spatial hearing and therefore many everyday listening tasks, such as understanding speech against a backdrop of competing sounds originating from various locations, and localization of sounds. For stimulation with bone conduction hearing devices (BCD), used to alleviate conductive hearing losses, limited transcranial attenuation results in cross-stimulation so that both cochleae are stimulated from the position of the bone conduction transducer. As such, interaural time and level differences, hallmarks of binaural hearing, are unpredictable at the level of the inner ears. The aim of this study was to compare spatial hearing by unilateral and bilateral BCD stimulation in normal-hearing listeners with simulated bilateral conductive hearing loss. DESIGN: Bilateral conductive hearing loss was reversibly induced in 25 subjects (mean age = 28.5 years) with air conduction and bone conduction (BC) pure-tone averages across 0.5, 1, 2, and 4 kHz (PTA 4 ) <5 dB HL. The mean (SD) PTA 4 for the simulated conductive hearing loss was 48.2 dB (3.8 dB). Subjects participated in a speech-in-speech task and a horizontal sound localization task in a within-subject repeated measures design (unilateral and bilateral bone conduction stimulation) using Baha 5 clinical sound processors on a softband. For the speech-in-speech task, the main outcome measure was the threshold for 40% correct speech recognition when masking speech and target speech were both colocated (0°) and spatially and symmetrically separated (target 0°, maskers ±30° and ±150°). Spatial release from masking was quantified as the difference between colocated and separated masking and target speech thresholds. For the localization task, the main outcome measure was the overall variance in localization accuracy quantified as an error index (0.0 = perfect performance; 1.0 = random performance). Four stimuli providing various spatial cues were used in the sound localization task. RESULTS: The bilateral BCD benefit for recognition thresholds of speech in competing speech was statistically significant but small regardless if the masking speech signals were colocated with, or spatially and symmetrically separated from, the target speech. Spatial release from masking was identical for unilateral and bilateral conditions, and significantly different from zero. A distinct bilateral BCD sound localization benefit existed but varied in magnitude across stimuli. The smallest benefit occurred for a low-frequency stimulus (octave-filtered noise, CF = 0.5 kHz), and the largest benefit occurred for unmodulated broadband and narrowband (octave-filtered noise, CF = 4.0 kHz) stimuli. Sound localization by unilateral BCD was poor across stimuli. CONCLUSIONS: Results suggest that the well-known transcranial transmission of BC sound affects bilateral BCD benefits for spatial processing of sound in differing ways. Results further suggest that patients with bilateral conductive hearing loss and BC thresholds within the normal range may benefit from a bilateral fitting of BCD, particularly for horizontal localization of sounds.

X-linked Malformation Deafness: Neurodevelopmental Symptoms Are Common in Children With IP3 Malformation and Mutation in POU3F4.

OBJECTIVE: Incomplete partition type 3 (IP3) malformation deafness is a rare hereditary cause of congenital or rapid progressive hearing loss. The children present with a severe to profound mixed hearing loss and temporal bone imaging show a typical inner ear malformation classified as IP3. Cochlear implantation is one option of hearing restoration in severe cases. Little is known about other specific difficulties these children might exhibit, for instance possible neurodevelopmental symptoms. MATERIAL AND METHODS: Ten 2; 0 to 9; 6-year-old children with IP3 malformation deafness (nine boys and one girl) with cochlear implants were evaluated with a retrospective chart review in combination with an additional extensive multidisciplinary assessment day. Hearing, language, cognition, and mental ill-health were compared with a control group of ten 1; 6 to 14; 5-year-old children with cochlear implants (seven boys and three girls) with another genetic cause of deafness, mutations in the GJB2 gene. RESULTS: Mutations in POU3F4 were found in nine of the 10 children with IP3 malformation. Children with IP3 malformation deafness had an atypical outcome with low level of speech recognition (especially in noise), executive functioning deficits, delayed or impaired speech as well as atypical lexical-semantic and pragmatic abilities, and exhibited mental ill-health issues. Parents of children with IP3 malformation were more likely to report that they were worried about their child's psychosocial wellbeing. Controls, however, had more age-typical results in all these domains. Eight of 10 children in the experimental group had high nonverbal cognitive ability despite their broad range of neurodevelopmental symptoms. CONCLUSIONS: While cochlear implantation is a feasible alternative for children with IP3 malformation deafness, co-occurring neurodevelopmental anomalies, such as attention deficit hyperactivity or developmental language disorder, and mental ill-health issues require an extensive and consistent multidisciplinary team approach during childhood to support their overall habilitation.

What Is the Early/Mid-term Survivorship and Functional Outcome After Bernese Periacetabular Osteotomy in a Pediatric Surgeon Practice?

BACKGROUND: The Bernese periacetabular osteotomy (PAO) is a recognized joint-preserving procedure. Achieving joint stability without creating impingement is important, but the orientation target that best balances these sometimes competing goals has not yet been clearly defined. Moreover, the learning curve of this challenging procedure has not been described. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the 10-year survivorship and functional outcome after Bernese PAO in a single-surgeon series; (2) to review which patient, surgical, and radiographic factors might predict outcome after the procedure; and (3) to define the learning curve for target acetabular correction. METHODS: The first 68 PAOs performed for symptomatic hip dysplasia were retrospectively evaluated. None have been lost to followup with followup less than 2 years. Endpoints for the lost to followup (n = 2) are at the time of when last seen. During the study period, the same surgeon performed 562 pelvic osteotomies (including Salter, Pemberton, Dega and Chiari) and 64 shelf acetabuloplasties. Bernese PAO was used only for symptomatic dysplasia (center-edge angle < 25° and nonhorizontal acetabular roof) in developmentally mature hips without evidence of major joint incongruence or subluxation. Most patients were female (n = 49 [60 hips, 88%]); mean age at operation was 25 years (SD 7). Sixteen hips had previous hip procedures. The study's mean followup was 8 years (range, 2-18 years). Patient-reported functional outcome was obtained using the WOMAC score (best-worst: 0-96). Radiographic parameters of dysplasia (acetabular index [AI], center-edge angle [CEA], congruency, Tönnis grade, and joint space) were evaluated from preoperative and postoperative radiographs using computer software. RESULTS: The 10-year survival rate was 93% (95% confidence interval [CI], 82%-100%); four patients underwent further surgery to the hip in the study period. The mean WOMAC was 12 (range, 0-54). Factors that influenced survival included joint congruency (100% versus 78%; 95% CI, 61%-96%; p = 0.03) and acetabular orientation correction achieved (AIpostoperative < 15° [100% versus 65%; 95% CI, 43-88; p < 0.001] and CEApostoperative 20° to 40° [100% versus 71.9%; 52.8-100; p < 0.001]). Better WOMAC scores were seen if postoperative AI < 15° (7 versus 25, p = 0.005) and CEA between 20° and 40° (7 versus 23, p = 0.005) were achieved. The chances of obtaining acetabular correction within this range improved after the 20(th) procedure (30% versus 70%, p = 0.008). CONCLUSIONS: This study reports excellent results after Bernese PAO in the hands of an experienced pediatric hip surgeon. We advocate cautious correction of the acetabular fragment. Future studies should concentrate on how to determine what the optimal target is and how to achieve it intraoperatively, minimizing the learning curve associated with it. LEVEL OF EVIDENCE: Level III, therapeutic study.

Vestibular function in children with vestibulocochlear nerve aplasia/hypoplasia.

BACKGROUND: Infants and young children with vestibulocochlear nerve (VCN) hypoplasia/aplasia present with severe hearing loss and are candidates for cochlear implantation (CI). It is unknown whether vestibular function is related to CI outcome and if vestibular tests can guide the operation decision. AIMS/OBJECTIVES: Our aim was to describe the vestibular function in patients with VCN hypoplasia/aplasia before a possible CI. MATERIALS AND METHODS: Forty-two ears in 23 patients were tested between 2019 and 2022 with bone-conducted cervical vestibular evoked myogenic potentials (BCcVEMP), video head impulse test (vHIT) and miniice-water caloric test (mIWC). RESULTS: All ears could be tested with at least one vestibular test and 83% could be tested with more than one method. Twenty-nine ears (61%) showed normal function with at least one method. The presence of a normal response to any test doubled the likelihood of a measured hearing threshold after CI, the best predictors being the BCcVEMP and vHIT (p < 0.05). CONCLUSION: Canal function may represent a predictor of auditive pathway integrity with a possible favourable audiological outcome after CI operation. SIGNIFICANCE: Our results demonstrate high vestibular response rates suggesting a functioning pathway despite the radiological diagnosis.

Evaluation of Artificial Fixation of the Incus and Malleus With Minimally Invasive Intraoperative Laser Vibrometry (MIVIB) in a Temporal Bone Model.

BACKGROUND: A significant number of adults suffer from conductive hearing loss due to chronic otitis media, otosclerosis, or other pathologies. An objective measurement of ossicular mobility is needed to avoid unnecessarily invasive middle ear surgery and to improve hearing outcomes. METHODS: Minimally invasive intraoperative laser vibrometry provides a method that is compatible with middle ear surgery, where the tympanic membrane is elevated. The ossicles were driven by a floating mass transducer and their mobility was measured using a laser Doppler vibrometer. Utilising this method, we assessed both the absolute velocities of the umbo and incus long process as well as the incus-to-umbo velocity ratio during artificial fixation of the incus alone or incus and malleus together. RESULTS: The reduction of absolute velocities was 8 dB greater at the umbo and 17 dB at the incus long process for incus-malleus fixations when compared with incus fixation alone. Incus fixation alone resulted in no change to the incus-to-umbo velocity ratio where incus-malleus fixations reduced this ratio (-11 dB). The change in incus velocity was shown to be the most suitable parameter to distinguish between incus fixation and incus-malleus fixation. When the whole frequency range was analyzed, one could also differentiate these two fixations from previously published stapes fixation, where the higher frequencies were less affected. CONCLUSION: Minimally invasive intraoperative laser vibrometry provides a promising objective analysis of ossicular mobility that would be useful intraoperatively.

Occurrence of primary brain tumors in cochlear implant patients in Sweden between 1989 and 2014.

PURPOSE: Cochlear implants are widely used for hearing rehabilitation of deaf children with congenital deafness or adults with acquired severe-to-profound hearing loss. The sound processor antenna creates a radio frequency-electromagnetic field transmitting the sound signal to the implant, similar to that in a mobile phone. A recent case report suggested a relationship between cochlear implants and malignant glioma, and some epidemiological studies have suggested an increased glioma and acoustic neuroma risk associated with long hours of mobile phone use. An epidemiological study is warranted to evaluate such a relationship in patients with cochlear implants. PATIENTS AND METHODS: To examine whether this chronic radio frequency-electromagnetic field signaling is associated with an increased brain tumor risk, a population-based cohort study was performed examining all 2,748 patients receiving a cochlear implant in Sweden during the years 1989-2014. In all, 3,169 surgeries were performed in the total cohort. The expected occurrence of glioma, meningioma, and acoustic neuroma in the patient cohort was calculated using specific national incidence rates in the Swedish population. RESULTS: Four patients were diagnosed with a brain tumor during follow-up, three of them having meningioma compared with 0.95 expected (standardized incidence ratio =3.16, 95% CI 0.65-9.24), and one had glioma compared with 1.34 expected (standardized incidence ratio =0.75, 95% CI 0.02-4.15). No case of acoustic neuroma was observed compared with 0.09 expected. CONCLUSION: In this study, we did not find support for concerns raised in a previous case report regarding a potentially higher risk of glioma. The number of brain tumors observed was well within the numbers expected from national incidence figures. Although this was a relatively small cohort with a limited follow-up time, it is the largest epidemiological study to date to address this concern.

Minimally invasive laser vibrometry (MIVIB) with a floating mass transducer - A new method for objective evaluation of the middle ear demonstrated on stapes fixation.

Ossicular fixation through otosclerosis, chronic otitis media and other pathologies, especially tympanosclerosis, are treated by surgery if hearing aids fail as an alternative. However, the best hearing outcome is often based on knowledge of the degree and location of the fixation. Objective methods to quantify the degree and position of the fixation are largely lacking. Laser vibrometry is a known method to detect ossicular fixation but clinical applicability remains limited. A new method, minimally invasive laser vibrometry (MIVIB), is presented to quantify ossicle mobility using laser vibrometry measurement through the ear canal after elevating the tympanic membrane, thus making the method feasible in minimally invasive explorative surgery. A floating mass transducer provides a clinically relevant transducer to drive ossicular vibration. This device was attached to the manubrium and drove vibrations at the same angle as the longitudinal axis of the stapes and was therefore used to assess ossicular chain mobility in a fresh-frozen temporal bone model with and without stapes fixation. The ratio between the umbo and incus long process was shown to be useful in assessing stapes fixation. The incus-to-umbo velocity ratio decreased by 15 dB when comparing the unfixated situation to stapes fixation up to 2.5 kHz. Such quantification of ossicular fixation using the incus-to-umbo velocity ratio would allow quick and objective analysis of ossicular chain fixations which will assist the surgeon in surgical planning and optimize hearing outcomes.

A clinical approach to severe insulin resistance.

Extreme forms of insulin resistance are a rare cause of type 2 diabetes. However, individuals with severe insulin resistance pose unique diagnostic and therapeutic challenges, and have often acted as 'experiments of nature' providing important novel information regarding endocrine physiology and mechanistic insights relevant to the study of more common disorders. Progress in understanding the molecular pathogenesis of such syndromes is also beginning to yield novel therapeutic options. Severe insulin resistance typically presents in 1 of 3 ways: (1) disordered glucose metabolism including both diabetes and/or paradoxical hypoglycaemia; (2) acanthosis nigricans, a velvety hyperpigmentation of axilliary and flexural skin often associated with skin tags; or (3) hyperandrogenism in girls (hirsutism, oligo-/amenorrhoea and polycystic ovaries). Lipodystrophy is a major cause of severe insulin resistance and needs to be looked for very carefully, particularly in the patients with significant dyslipidaemia and fatty liver. Specific treatments are now available for some forms of severe insulin resistance; for example, leptin replacement in patients with generalized lipodystrophy. In the absence of a specific diagnosis and therapy, metformin is a useful insulin sensitizer and should be used in conjunction with aggressive diet and exercise interventions.

X-linked Malformation and Cochlear Implantation.

OBJECTIVE: To evaluate if cochlear implantation is safe and constitutes an option for hearing rehabilitation of children with x-linked inner ear malformation. STUDY DESIGN: Retrospective patient review in combination with a multidisciplinary follow-up. SETTING: Tertiary referral hospital and cochlear implant program. PATIENTS: Ten children with severe-profound mixed hearing loss and radiological findings consistent with Incomplete Partition type 3 cochlear malformation received cochlear implants during the years 2007 to 2015. Nine of the children had a mutation affecting the gene POU3F4 on Xq21. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Surgical events, intraoperative measures and electrical stimulation levels, hearing and spoken language abilities. RESULTS: In all, 15 cochlear implantations were performed. In three cases the electrode was found to be in the internal auditory canal on intraoperative x-ray and repositioned successfully. One child had a postoperative rhinorrhea confirmed to be cerebrospinal fluid but this resolved on conservative treatment. No severe complications occurred. Postoperative electrical stimulation levels were higher in 9 of 10 children, as compared with typically reported average levels in patients with a normal cochlea. Eight patients developed spoken language to various degrees while two were still at precommunication level. However, speech recognition scores were lower than average pediatric cases. CONCLUSION: Cochlear implantation is a safe procedure for children with severe-profound mixed hearing loss related to POU3F4 mutation inner ear malformation. The children develop hearing and spoken language but outcome is below average for pediatric CI recipients.

Precocious puberty secondary to massive ovarian oedema in a 6-month-old girl.

A 6-month-old girl was referred with breast and pubic hair development. Investigations excluded an adrenal or central cause for her precocity. Ovarian ultrasound scans showed bilaterally enlarged ovaries with both solid and cystic changes. A follow-up examination suggested progression of the precocity and in view of the young age of the child, and concerns regarding underlying malignancy, she underwent laparotomy. Histology showed no evidence of neoplasia but there was stromal oedema consistent with a diagnosis of massive ovarian oedema. This entity is poorly recognised in the paediatric literature as a cause of sexual precocity, and has never previously been described in such a young patient. This is an unusual cause of precocity in a young child and its recognition and management are reviewed.

Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid arthritis.

Rheumatoid arthritis is a multisystemic auto-inflammatory disease affecting up to 1% of the population and leading to the destruction of the joints. Evidence exists for the involvement of the innate as well as the adaptive immune systems in the pathology of the disease. The success of anti-tumour necrosis factor-alpha indicates the importance of pro-inflammatory mediators produced by innate immune cells in rheumatoid arthritis progression. Therefore, considerable efforts have been made in elucidating the signalling pathways leading to the expression of those mediators. This review will concentrate on the role of signalling pathways in innate immune cells in the context of rheumatoid arthritis.

Targeting intracellular signaling: a novel approach to vaccination.

Vaccination is well known to control many current infectious diseases. However, the development of cellular (Th1) immunity to control viral pathogens, among others, requires the development of new vaccine adjuvants. The use of Toll-like receptor ligands or cytokines has shown much promise, although specificity and toxicity are issues with these strategies. Targeting intracellular signaling pathways may allow for greater specificity of the adjuvant, as well as reducing systemic toxicity. Studies targeting these pathways are discussed, as well as their potential applications in the future.

The contributions of plasma IGF-I, IGFBP-3 and leptin to growth in extremely premature infants during the first two years.

We determined the contributions of IGF-I, IGFBP-3 and leptin to growth in extremely premature infants over the first two years. Weight (Wt), crown-to heel length (CHL), plasma IGF-I, IGFBP-3 and leptin were measured in infants (gestation 24-33 wk) at birth (n = 54), expected date of delivery (EDD) and 6, 12 and 24 mo post-EDD (n = 29). Area under the curve (AUC) for hormone levels was calculated over 4 periods: birth-EDD, EDD-200 d, EDD-350 d and EDD-700 d. IGFBP-3, but not IGF-I or leptin, on day 1 correlated with birth Wt SD scores (SDS) (r = 0.46, p = 0.002) and CHL SDS (r = 0.41, p = 0.01). Wt SDS at EDD correlated with AUC IGF-I, IGFBP-3 and leptin (birth-EDD), but leptin was the best predictor in multiple regression (r = 0.65, p < 0.0001). Wt at EDD + 700 d correlated with AUC leptin (EDD-700 d) (r = 0.62, p = 0.002). CHL SDS at EDD correlated with AUC IGFBP-3 and leptin (birth-EDD), but IGFBP-3 was the best predictor (r = 0.55, p < 0.0001). CHL at EDD + 700 d correlated with AUC IGF-I and IGFBP-3 (EDD-700 d), but IGFBP-3 was the best predictor (r = 0.47, p = 0.01). Wt and CHL at birth were associated with IGFBP-3 levels in these infants. Wt at EDD and EDD + 700 d was predicted by concurrent leptin output while linear growth at EDD and EDD + 700 d was predicted by IGFBP-3 output.

Respiratory infections: do we ever recover?

Although the outcome of respiratory infection alters with age, nutritional status, and immunologic competence, there is a growing body of evidence that we all develop a unique but subtle inflammatory profile. This uniqueness is determined by the sequence of infections or antigenic insults encountered that permanently mold our lungs through experience. This experience and learning process forms the basis of immunologic memory that is attributed to the acquired immune system. But what happens if the pathogen is not homologous to any preceding it? In the absence of cross-specific acquired immunity, one would expect a response similar to that of a subject who had never been infected with anything before. It is now clear that this is not the case. Prior inflammation in the respiratory tract alters immunity and pathology to subsequent infections even when they are antigenically distinct. Furthermore, the influence of the first infection is long lasting, not dependent on the presence of T and B cells, and effective against disparate pathogen combinations. We have used the term "innate imprinting" to explain this phenomenon, although innate education may be a closer description. This educational process, by sequential waves of infection, may be beneficial, as shown for successive viral infections, or significantly worse, as illustrated by the increased susceptibly to life-threatening bacterial pneumonia in patients infected with seasonal and pandemic influenza. We now examine what these long-term changes involve, the likely cell populations affected, and what this means to those studying inflammatory disorders in the lung.

Measurement and the newborn infant.

Measurement of newborn babies is widely regarded as being too inaccurate to justify its regular practice. It is common for infants to be weighed at birth and for no other measurements to be made. Although such assumptions are superficially correct, it is possible to train people to perform accurate measurements and for improved performance to be sustained. Accurate sequential measurements are possible and provide more information than single measurements. Detailed measurements show that postnatal growth may change rapidly and dramatically, particularly in preterm infants. Postnatal growth impairment is common in such infants and may be sustained. Limited evidence suggests that there may be a significant reduction in final stature. Preliminary data also suggest that many preterm infants may also show evidence of alterations in biochemical and physiological variables consistent with early programming and the potential for altered disease susceptibility in adult life.