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  • 1.
    Erlandsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holm, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Schindele, Alexandra
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Balloon dilatation versus CO2 laser surgery in subglottic stenosis: a retrospective analysis of therapeutic approaches2023In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 143, no 6, p. 528-535Article in journal (Refereed)
    Abstract [en]

    Background: Subglottic stenosis (SGS) is a narrowing of the airway just below the vocal folds. The cause of SGS and the optimal care for these patients, have remained elusive. Endoscopic surgery of SGS using either balloon or CO2 laser is associated with recurrence.

    Aims and objectives: Our aim is to compare surgery free intervals (SFI) between these two methods applied in two different timeframes. The knowledge gained from this project can support decision-making regarding surgical method choice.

    Material and methods: Participants were retrospectively identified using medical records between 1999–2021. We used pre-defined broad inclusion criteria to identify cases using the International Classification of Disease (ICD-10). Primary outcome was surgery free intervals.

    Results: 141 patients were identified, 63 met the criteria for SGS, and were included in the analysis. Results show no significant difference in SFI, comparing balloon dilatation and CO2 laser.

    Conclusion: These findings demonstrate no detected difference in treatment intervals (SFI) when comparing these two commonly used surgical alternatives for SGS.

    Significance: The outcome of this report supports surgical freedom of choice based on the surgeon’s experience and skill and ushes for further studies on patient experience regarding these two therapeutic approaches.

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  • 2.
    Koro, Eleonor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lundgren, Elenor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Smeds, Henrik
    Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Long-term follow-up in active transcutaneous bone conduction implants2023In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 45, no 1, p. 58-64Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate long-term outcomes of active transcutaneous bone conduction implants (atBCIs) regarding safety, hearing, and quality of life.

    Study design: A clinical study with retrospective medical record analysis combined with prospective audiometry and quality of life questionnaires.

    Setting: Three secondary to tertiary care hospitals.

    Patients: All subjects operated with an atBCI in three regions in Sweden were asked for informed consent. Indications for atBCI were single-sided deafness (SSD) and conductive or mixed hearing loss (CMHL).

    Intervention: Evaluation of atBCI.

    Main Outcome Measures: Pure tone and speech audiometry and Glasgow Benefit Inventory (GBI).

    Result: Thirty-three subjects were included and 29 completed all parts. The total follow-up time was 124.1 subject-years. Nineteen subjects had CMHL and in this group, pure tone averages (PTA4) were 56.6 dB HL unaided and 29.6 dB HL aided, comparable with a functional gain of 26.0 dB. Effective gain (EG) was −12.7 dB. With bilateral hearing, Word Recognition Scores (WRS) in noise were 36.5% unaided and 59.1% aided. Fourteen subjects had SSD or asymmetric hearing loss (AHL) and in this group, PTA4 were >100 dB HL unaided and 32.1 dB HL aided with the contralateral ear blocked. EG was −9.1 dB. With bilateral hearing, WRSs were 53.2% unaided and 67.9% aided. The means of the total GBI scores were 31.7 for CMHL and 23.6 for SSD/AHL.

    Conclusion: Few complications occurred during the study. The atBCI is concluded to provide a safe and effective long-term hearing rehabilitation.

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  • 3.
    Koro, Eleonor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Outcomes after Application of Active Bone Conducting Implants2019In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 24, no 4, p. 197-205Article in journal (Refereed)
    Abstract [en]

    Background: A bone conducting implant is a treatment option for individuals with conductive or mixed hearing loss (CHL, MHL) who do not tolerate regular hearing aids, and for individuals with single-sided deafness (SSD). An active bone conducting implant (ABCI) was introduced in 2012 with indication in CHL, MHL, and SSD, and it is still the only ABCI available. With complete implantation of the active transducer and consequent intact skin, a decrease in infections, skin overgrowth, and implant losses, all common disadvantages with earlier passive bone conducting implants, could be expected. Our Ear, Nose and Throat Department, a secondary care center for otosurgery that covers a population of approximately 365,000 inhabitants, was approved to implant ABCIs in 2012.

    Objectives: Our aim was to conduct an evaluation of audiological and subjective outcomes after ABCIs.

    Method: A cohort study with retrospective and prospective data collection was performed.The first 20 consecutive patients operated with an ABCI were asked for informed consent. The main outcome measures werepure tone and speech audiometry and the Glasgow Benefit Inventory (GBI).

    Results: Seventeen patients accepted to participate and 15 were able to complete all parts. Six patients had CHL or MHL. In this group the pure tone audiometry tests are comparable with an average functional hearing gain of 29.8 dB HL. With bilateral hearing, the mean Word Recognition Score (WRS) in noise was 35.7% unaided and 62.7% aided. Ten patients had the indication SSD. With the hearing ear blocked, the pure tone average was >101 dB HL, compared to 29.3 dB HL in sound field aided. With bilateral hearing, the mean WRS in noise was 59.7% unaided and 72.8% aided. The mean of the total GBI score was 42.1 in the group with CHL or MHL and 20.6 in the group with SSD.

    Conclusions: The patients benefit from their implants in terms of quality of life, and there is a substantial hearing gain from the implant for patients with conductive or MHL. Patients with SSD benefit less from the implant than other diagnoses but the positive outcomes are comparable to other options for this group.

  • 4.
    Koro, Eleonor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ögren, Emely
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Olofsson, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Evaluation of magnetic resonance imaging to detect cholesteatoma in clinical healthcare2024In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 144, no 3, p. 193-197Article in journal (Refereed)
    Abstract [en]

    Background: Non-Echo-Planar Diffusion Weighed Magnetic Resonance Imaging (non-EPI DW MRI) plays a role in the planning of cholesteatoma surgery.

    Objectives: To outline the usage of Non-EPI DW MRI in cholesteatoma diagnostics and to determine its accuracy, using otosurgery diagnostics as reference standard. Material and

    Methods: A retrospective descriptive study. All subjects operated, with suspicion of cholesteatoma as indication, that had a preceding examination with non-EPI DW MRI, between October 2010 and March 2019. Calculating sensitivity, specificity, predicative values, and likelihood ratios, using non-EPI DW MRI as index test and diagnosis from otosurgery as reference standard.

    Results: Fifty-two subject episodes were included. Non-EPI DW MRI had a sensitivity of 0.50, specificity of 0.75, positive and negative predictive values of 0.74 and 0.52 and, positive and negative likelihood ratios of 2.0 and 0.67 respectively.

    Conclusions and Significance: There is a clear annual trend with increased numbers of executed examinations during the study period. The diagnostic accuracy of non-EPI DW MRI does not reach acceptable levels in the existing everyday routine practice conditions. The accuracy of the examination increases when interpreted by an experienced radiologist and when using the definition of cholesteatoma recommended by EAONO/JOS.

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  • 5.
    Rönnblom, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Niklasson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forces Required for Isolated Malleus Shaft Fractures2021In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 42, no 10, p. 1515-1520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND HYPOTHESIS: Isolated malleus shaft fractures are rare cases. A commonly reported cause is a finger pulled out from a wet outer ear canal after a shower or bath. The objective was to investigate experimentally the mechanism and forces needed to establish an isolated malleus shaft fracture.

    METHODS: Ten fresh-frozen human temporal bones were adapted to allow visual inspection of the structures involved while negative pressure trauma was applied. Thirty malleus bones were broken and the required forces were measured. Measurements from 60 adult test subjects were used to create mathematical and physical models to calculate and measure the forces necessary for generating trauma. To calculate the maximum muscle force developed by the tensor tympani muscle, the muscle area and fiber type composition were determined.

    RESULTS: The temporal bone experiments showed that applied negative pressure in a wet ear canal could not fracture the malleus shaft with only passive counterforce from supporting structures, although the forces exceeded what was required for a malleus shaft fracture. When adding calculated counteracting forces from the tensor tympani muscles, which consisted of 87% type II fibers, we estimate that a sufficient force is generated to cause a malleus fracture.

    CONCLUSION: The combination of a negative pressure created by a finger pulling outward in a wet ear canal and a simultaneous counteracting reflexive force by the tensor tympani muscle were found to be sufficient to cause an isolated malleus fracture with an intact tympanic membrane.

  • 6.
    Werner, Mimmi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hair cell regeneration in vestibular epithelia: a study in an in vitro model2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Hair cells (HCs) are the sensory receptors in both the auditory and the vestibular organs of the inner ear. Supporting cells (SCs) are non-sensory cells embracing the HCs. Injuries of the HCs by aging, acoustic trauma or ototoxic drugs (mainly aminoglycosides, e.g. gentamicin) and cisplatin, often cause permanent impairment of hearing and balance. Birds and amphibians can regenerate their auditory and vestibular HCs after injury through proliferation of SCs or direct transdifferentiation of a SC into a HC. For mammals this ability is limited and spontaneous HC regeneration occurs only in the vestibular sensory epithelia. The utricle is one of the five vestibular organs and contributes to our balance by registering linear acceleration and head tilts. The aim of this PhD thesis was to investigate morphological and morphometric events during spontaneous HC regeneration following gentamicin exposure in neonatal rat utricular explants.

    Methods

    Long-term organ culture of macula utriculi, which is stable and reproducible for up to 28 days in vitro (DIV), was used in all papers in the thesis. HC damage was induced by gentamicin. On 2 DIV the explanted utricular maculae were divided into two groups, a control group and a gentamicin-exposed group. In the latter group macular explants were exposed to gentamicin for 48 hours during 2-3 DIV and then allowed to recover. Morphologic and morphometric evaluations were done from utricles harvested at various time points during 28 DIV. Imaging techniques used were light microscopy, including immunohistochemistry, and transmission electron microscopy.

    Results

    In the control group the epithelia were well preserved with a slight decline in HC density after 14 DIV. In the gentamicin-exposed group there was an initial substantial decline in HC density and thereafter the proportion of HCs in relation to SCs increased significantly. Using BrdU as a proliferation marker and myosin 7a as a HC marker, we found no cells that were double marked. At the ultrastructural level, the apical occlusion of the explanted epithelia was intact in both the control and the gentamicin exposed group during the entire in vitro period. Cells that seemed to be in a transitional state, transforming from SCs into HCs were observed in the gentamicin-exposed group. These cells had cytoplasmic extensions basally i.e. foot processes, an assembly of mitochondria basally in the cell or in these foot processes, and often apical SC extensions covering the HC. HCs classified as transitional cells had an increased number of SC connections to their basal parts compared to mature HCs.

    Conclusions 

    In these neonatal rat utricular explants:

    - The morphological structure of the sensory epithelia was well preserved during long-term culture.

    - The renewal of hair cells after gentamicin exposure occurred through direct transdifferentiation of supporting cells into hair cells.

    - There was also a proliferative response by the supporting cells, but this supporting cell proliferation did not contribute to the generation of new hair cells.

    - Cells in a transitional state, showing a characteristic morphology, were observed during the process of transdifferentiation from supporting cells into hair cells.

    - The tight junctional seal of the epithelia stayed morphologically intact also after gentamicin exposure.

    - Gap junctions were observed in between supporting cells but not found in between hair cells and supporting cells or between transitional cells and supporting cells.

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  • 7.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Canlon, Barbara
    Viberg, Agneta
    Van De Water, Thomas R.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Role of Transdifferentiation/Proliferation in Vestibular Hair Cell Renewal within Ototoxin-challenged Utricle ExplantsManuscript (preprint) (Other academic)
  • 8.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Andersson, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characteristics of vestibular hair cells and support cells in long term cultures of rat utricle explants2012In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 283, no 1-2, p. 107-116Article in journal (Refereed)
    Abstract [en]

    A method for long term culture of utricular macula explants is demonstrated to be stable and reproducible over a period of 28 days in vitro (DIV). This culture system for four-day-old rat utricular maculae is potentially suitable for studies of hair cell loss, repair and regeneration processes as they occur in post-natal mammalian inner ear sensory epithelia. The cellular events that occur within utricular macula hair cell epithelia during 28 days of culture are documented from serial sections. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) and the assistance of morphometric computer software. Ultrastructural observations were made with transmission electron microscopy (TEM) for describing the changes in the fine detailed morphological characteristics that occurred in the explants related to time in vitro. After 2 DIV the density of HCs was 77%, at 21 DIV it was 69%, and at 28 DIV it was 52% of HCs present at explantation. Between 2 DIV and 28 DIV there was a 1.7% decrease of the vestibular macula HC density per DIV. The corresponding decrease of SC density within the utricular explants was less than 1% per DIV. The overall morphology of the epithelia, i.e. relationship of HCs to SCs, was well preserved during the first two weeks in culture. After this time a slight deterioration of the epithelia was observed and although type I and type II HCs were identified by TEM observations, these two HC types could no longer be distinguished from one another by LM observations. In preparations cultured for 21 DIV, SC nuclei were located more apical and further away from the basal membrane compared to their position in macula explants fixed immediately after dissection. The loss of cells that occurred was probably due to expulsion from the apical (i.e. luminal) surface of the sensory epithelia, but no lesions of the apical lining or ruptures of the basal membrane were observed. There were no significant changes in the volume of the vestibular HC comprising macular epithelium during the observation period of 28 DIV.

  • 9.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants2015In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 321, p. 1-11Article in journal (Refereed)
    Abstract [en]

    We have studied aminoglycoside-induced vestibular hair-cell renewal using long-term culture of utricular macula explants from 4-day-old rats. Explanted utricles were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro (DIV), and then recovering in unsupplemented medium. Utricles were harvested at specified time points from the 2nd through the 28th DIV. The cellular events that occurred within hair cell epithelia during the culture period were documented from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) with the assistance of morphometric software. Ultrastructural observations were made from selected specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four days after gentamicin exposure, the density of HCs was 11% of the number of HCs observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was 61% of the number of HCs observed in the control group explant specimens. Simultaneously with this increase in HCs there was a corresponding decline in the number of SCs within the epithelium. The proportion of HCs in relation to SCs increased significantly in the gentamicin-exposed explant group during the 5th to the 28th DIV period of culture. There were no significant differences in the volume estimations of the gentamicin-exposed and the control group explants during the observed period of culture. Morphological observations showed that gentamicin exposure induced extensive loss of HCs within the epithelial layer, which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11 days after gentamicin exposure) a pseudostratified epithelium with multiple layers of disorganized cells was observed. At 21 DIV new HCs were observed that also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs with several layers of SCs located more basally characterized the gentamicin-exposed epithelium. No mitoses were observed within the epithelial layer of any explants. Our conclusion is that direct transdifferentiation of SCs into HCs was the only process contributing to the renewal of HCs after gentamicin exposure in these explants of vestibular inner ear epithelia obtained from the labyrinths of 4-day-old rats.

  • 10.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Hair cell characteristics after hair cell renewal-An ultrastructural study of gentamicin exposed rat utricular explantsManuscript (preprint) (Other academic)
  • 11.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants2020In: The Anatomical Record: advances in integrative anatomy and evolutionary biology, ISSN 1932-8486, Vol. 303, no 3, p. 506-515Article in journal (Refereed)
    Abstract [en]

    The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs within the balance organs of mammalian inner ears. This low-level renewal of vestibular HCs exists during normal conditions and it is further enhanced after trauma-induced loss of these HCs. The main process for renewal of HCs within mammalian vestibular epithelia is a conversion/transdifferentiation of existing supporting cells (SCs) into replacement HCs.In earlier studies using long-term organ cultures of postnatal rat macula utriculi, HC loss induced by gentamicin resulted in an initial substantial decline in HC density followed by a significant increase in the proportion of HCs to SCs indicating the production of replacement HCs. In the present study, using the same model of ototoxic damage to study renewal of vestibular HCs, we focus on the ultrastructural characteristics of SCs undergoing transdifferentiation into new HCs. Our objective was to search for morphological signs of SC plasticity during this process. In the utricular epithelia, we observed immature HCs, which appear to be SCs transdifferentiating into HCs. These bridge SCs have unique morphological features characterized by formation of foot processes, basal accumulation of mitochondria, and an increased amount of connections with nearby SCs. No gap junctions were observed on these transitional cells. The tight junction seals were morphologically intact in both control and gentamicin-exposed explants. 

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