Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice

Magnetic resonance imaging features of large endolymphatic sac compartments: audiological and clinical correlates

Abstract Objectives: (1) To study the prevalence and characteristics of large endolymphatic sac internal compartments on thin-section T2- and T2*-weighted magnetic resonance imaging, and to relate these to other large endolymphatic sac magnetic resonance imaging features, and (2) to correlate the compartment imaging features, endolymphatic sac size and labyrinthine anomalies with the patients' clinical and audiological data. Method: Magnetic resonance imaging studies for 38 patients with large endolymphatic sac anomalies were retrospectively reviewed in a tertiary referral centre. Endolymphatic sac compartment presence, morphology and imaging signal were assessed. Endolymphatic sac size and labyrinthine anomalies were also recorded. Endolymphatic sac compartments and other imaging features were correlated with clinical and audiological data. Results: Compartments were present in 57 per cent of the imaged endolymphatic sacs, but their presence alone did not correlate with other imaging features or clinical data. The endolymphatic sac:internal auditory meatus signal ratio was associated with a history of sudden or fluctuating hearing loss. Hearing loss correlated with opercular and extraosseous endolymphatic sac size measurements. A larger midpoint intraosseous endolymphatic sac size was associated with clear fluid loss at cochlear implantation. Conclusion: The magnetic resonance imaging characteristics of large endolymphatic sac compartments have been defined. The endolymphatic sac size and distal compartment signal should be recorded, as these provide prognostic information and assist the planning of appropriate intervention

Technologies of memory: practices of remembering in analogue and digital photography

This article demonstrates the need always to consider change against continuity and continuity against change in the analysis of mnemonic technologies. It does so by exploring what has happened in the move from analogue to digital photography, looking in particular at how this has affected the meanings of personal photographs and the practices of remembering associated with them. In contrast with technologically determinist perspectives which have been, however latently, manifest in writing on new media, the value of exploring vernacular photography as a specifically mnemonic practice is that it turns our attention to the ways in which photographic practices are bound up with longer-term social uses and cultural values. Our analysis focuses on changes in four key categories of photographic practice that relate to the analogue/digital shift: photo-taking; photo-storing; photo-viewing; photo-sharing – all of which have consequences for the uses of photography as a mnemonic resource. They have all been altered in varying degrees by the advent of digital technologies, but with people continually making comparative evaluations of old and new, drawing on the former as a key aspect of learning how to use the latter

A systematic review on prevention and management of wound infections from cochlear implantation.

OBJECTIVE OF REVIEW: Surgical site infections are a recognised complication of cochlear implant (CI) surgery with significant morbidity. Our aim was to search for the optimum prevention and management strategy to deal with this issue. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A systematic literature search was undertaken from the databases of Embase, CINAHL, MEDLINE® , Web of Science, Scopus and Cochrane Library according to the predefined inclusion and exclusion criteria. EVALUATION METHOD: All relevant titles, abstracts and full-text articles were reviewed by two authors who resolved any differences by discussion and consultation with senior authors. RESULTS: Fourteen articles were included in our review. The overall quality of evidence was low with the vast majority of the studies being retrospective case series and expert opinions. No randomised controlled trials were noted. We found consistent reports that intraoperative prophylactic antibiotics should be given to all patients undergoing CI and that the vast majority of CI wound infections had grown Staphylococcal spp. or Pseudomonas spp. CONCLUSION: Our review has not identified any reliable or reproducible strategies to prevent and deal with wound infections after CI. We strongly encourage further research within this field and would suggest that a consensus of opinions from a multidisciplinary panel of experts may be a pragmatic way forward as an effective guide

Transient Inhibition of PI3Kδ Enhances the Therapeutic Effect of Intravenous Delivery of Oncolytic Vaccinia Virus

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy

Protocol for a multicentre randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss:The STARFISH trial

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model

Generating operative workflows for vestibular schwannoma resection: a two-stage Delphi consensus in collaboration with British Skull Base Society. Part 1: the retrosigmoid approach

Objective: An operative workflow systematically compartmentalises operations into hierarchal components of phases, steps, instrument, technique errors and event errors. Operative workflow provides a foundation for education, training, and understanding of surgical variation. In Part 1 we present a codified operative workflow for the retrosigmoid approach to vestibular schwannoma resection. / Methods: A mixed-method consensus process of literature review, small group Delphi consensus, followed by a national Delphi consensus was performed in collaboration with British Skull Base Society (BSBS). Each Delphi round was repeated until data saturation and over 90% consensus was reached. / Results: Eighteen consultant skull base surgeons (10 neurosurgeons; 8 ENT) with median 17.9 years of experience (IQR 17.5 years) of independent practice participated. There was a 100% response rate across both Delphi rounds. The operative workflow for the retrosigmoid approach contained 3 phases and 40 unique steps: Phase 1: approach and exposure; Phase 2: tumour debulking and excision; Phase 3: closure. For the retrosigmoid approach, technique and event error for each operative step was also described. / Conclusions: We present Part 1 of a national, multi-centre, consensus-derived codified operative workflow for the retrosigmoid and approach to vestibular schwannomas that encompasses phases, steps, instruments, technique errors, and event errors. The codified retrosigmoid approach presented in this manuscript can serve as foundational research for future work, such as operative workflow analysis or neurosurgical simulation and education

Generating Operative Workflows for Vestibular Schwannoma Resection: A Two-Stage Delphi's Consensus in Collaboration with the British Skull Base Society. Part 2: The Translabyrinthine Approach

Objective An operative workflow systematically compartmentalizes operations into hierarchal components of phases, steps, instrument, technique errors, and event errors. Operative workflow provides a foundation for education, training, and understanding of surgical variation. In this Part 2, we present a codified operative workflow for the translabyrinthine approach to vestibular schwannoma resection. Methods A mixed-method consensus process of literature review, small-group Delphi's consensus, followed by a national Delphi's consensus was performed in collaboration with British Skull Base Society (BSBS). Each Delphi's round was repeated until data saturation and over 90% consensus was reached. Results Seventeen consultant skull base surgeons (nine neurosurgeons and eight ENT [ear, nose, and throat]) with median of 13.9 years of experience (interquartile range: 18.1 years) of independent practice participated. There was a 100% response rate across both the Delphi rounds. The translabyrinthine approach had the following five phases and 57 unique steps: Phase 1, approach and exposure; Phase 2, mastoidectomy; Phase 3, internal auditory canal and dural opening; Phase 4, tumor debulking and excision; and Phase 5, closure. Conclusion We present Part 2 of a national, multicenter, consensus-derived, codified operative workflow for the translabyrinthine approach to vestibular schwannomas. The five phases contain the operative, steps, instruments, technique errors, and event errors. The codified translabyrinthine approach presented in this manuscript can serve as foundational research for future work, such as the application of artificial intelligence to vestibular schwannoma resection and comparative surgical research

CSF Rhinorrhoea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 1:Multicenter Pilot Study

Background CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective, multicentre observational study seeking to determine: (1) the scope of skull base repair methods used; and (2) corresponding rates of postoperative CSF rhinorrhoea in endonasal transsphenoidal (TSA) expanded endonasal approaches (EEA) for skull base tumours. We sought to pilot the project - assessing the feasibility and acceptability by gathering preliminary data. Methods A prospective, observational cohort pilot study was carried out at twelve tertiary UK neurosurgical units. Feedback regarding project positives and challenges were qualitatively analysed. Results 187 cases were included, 159 TSA (85%) and 28 EEA (15%). The most common pathologies included: pituitary adenomas (n=141/187), craniopharyngiomas (n=13/187) and skull-base meningiomas (n=4/187). The most common skull base repair techniques used were tissue glues (n=132/187, most commonly Tisseel®), grafts (n=94/187, most commonly fat autograft or Spongostan™) and vascularised flaps (n=51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n=125/187) and lumbar drains (n=22/187). Biochemically-confirmed CSF rhinorrhoea occurred in 6/159 (3.8%) TSA and 2/28 (7.1%) EEA. Four TSA (3%) and two EEA (7%) cases required operative management for CSF rhinorrhoea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included: user-friendly and efficient data collection, strong support from senior team members) demonstrating acceptability. Conclusions Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicentre dissemination of this project, in order to establish a benchmark of contemporary skull base neurosurgery practice, particularly with respect to EEA cases. Keywords Cerebrospinal fluid rhinorrhoeaCSFCerebrospinal fluid leakskull base surgeryendoscopic endonasalEE