Reconstructive ossiculoplasty options in primary cholesteatoma surgeries with an intact stapes.

PURPOSE: In primary cholesteatoma patients, incus destruction with an intact and mobile stapes is a frequent finding. Different techniques have been described to restore the ossicular chain, including incus interposition, stapes augmentation and type III tympanoplasty. Controversy about postoperative hearing results in open versus closed surgical techniques exist. METHODS: We performed a retrospective analysis of clinical, surgical and audiometric data of patients with primary cholesteatoma surgery operated between 2010 and 2020, and a mobile stapes and one-stage ossicular reconstruction. Pre- and post-operative audiograms were compared for the different surgical groups, mainly focusing on postoperative air-bone gap. Mastoid pneumatization and ventilation was also considered. RESULTS: The mean postoperative air-bone gap (0.5-4 kHz) of the 126 included patients was 20 dB. Hearing after type III tympanoplasty (26 dB) was worse than incus interposition (19 dB) and stapes augmentation (20 dB). Hearing after an open (23 dB) versus closed (19 dB) surgical technique was significantly different. No improvement in air-bone gap was observed for the higher frequencies. CONCLUSION: A residual postoperative air-bone gap should be considered after primary cholesteatoma surgery with intact and mobile stapes. Incus interposition in closed cavity operation is the optimal situation, but open cavity surgery should not be avoided because of hearing. Extent of the disease is prioritized and poorer ventilation before and after surgery may affect postoperative hearing.

A tailored approach in cholesteatoma surgery.

PURPOSE: In recent years, new techniques have been added to cholesteatoma surgery, and established microsurgical approaches are being reconsidered. This study aims to present the importance of individualized decision-making for the selection of an intact canal wall (CWU) or canal wall down (CWD) surgical procedure for each patient. METHODS: Using the "ChOLE" classification we categorized 264 operations retrospectively. 162 CWU and 102 CWD surgeries were performed. We focus to determine why a CWD procedure was chosen quite frequently despite some low-stage cases. Furthermore, we evaluated recidivism and hearing outcomes. RESULTS: Smaller cholesteatomas (Ch-stage 1a, 1b & 2a) were found in 182 patients (70%), ossicular chain status feasible for straightforward reconstruction (O-stage 0, 1 & 2) was present in 186 patients (70%), minor complications due to the cholesteatoma (L-stage 1) were infrequent with 28 cases (11%) and a well-pneumatized mastoid was found in 144 cases (55%). Recidivism rates were low (7%) without any difference in both groups and a mean follow-up time of 4 years and 8 months. In primary surgeries there was a significant difference (p < 0.05) in postoperative mean air-bone gap (ABG) between CWU (17dB) and CWD (27dB). CONCLUSION: The main goals of cholesteatoma surgery remain the avoidance of recidivism and optimal hearing rehabilitation. We recommend a tailored approach in the treatment of cholesteatomas and not a dogmatic one. Surgeons should not hesitate to perform a CWD procedure if required. Performed correctly it results in a dry ear and CWD surgery should remain in the skill set of the otologic surgeon.

[Role of computed tomography in the preoperative diagnosis of otosclerosis]. / Stellenwert der Computertomographie in der präoperativen Diagnostik der Otosklerose.

BACKGROUND: Otosclerosis is an osteodystrophy of the otic capsule and presents with progressive conductive hearing loss. Imaging studies, especially computed tomography (CT) and cone-beam CT, have gained increased relevance in the diagnosis of otosclerosis. OBJECTIVE: This study investigated whether there is a correlation between the extent of otosclerosis in high-resolution or cone-beam CT and hearing loss in pure-tone audiometry. MATERIALS AND METHODS: Based on an existing classification of otosclerotic foci, a classification was established. Preoperative CT scans of patients undergoing stapedotomy between 2015 and 2019 were evaluated and classified by two independent otorhinolaryngologists. The preoperative pure-tone audiograms were analysed and compared to the results of CT. RESULTS: A total of 168 CT studies (i.e., 168 ears) in 156 patients with intraoperatively confirmed otosclerosis were included in our study. A correlation between the extent of the otosclerotic focus or the calculated scores and hearing loss in pure-tone audiometry (air conduction, bone conduction and air-bone-gap) could not be proven. CONCLUSION: Preoperative CT is not obligatory. However, preoperative imaging using CT or cone-beam CT can be helpful to confirm the diagnosis and exclude other middle or inner ear pathologies as well as in planning of the surgical procedure in the overall context of otoscopy and audiometry. A correlation with the degree of hearing impairment could not be demonstrated and remains unclear.

[Treatment of single-sided deafness by cochlear implantation]. / Traitement de la surdité unilatérale par l'implant cochléaire.

Single sided deafness diminishes speech understanding in noise and sound localization and thereby globally auditory performance. Most patients also suffer from tinnitus and indicate reduced quality of life. Patients have the choice to adapt to the new situation without treatment, to restore pseudostereophonic hearing by contralateral routing of signal (CROS) hearing aids or to restore binaural hearing using a cochlear implant in the deaf ear. This article summarizes the physiological base of binaural hearing and treatment options for single sided deafness with a special emphasis on the cochlear implant.

La surdité unilatérale diminue la compréhension dans le bruit et la capacité de localiser les sources sonores affectant ainsi globalement la performance auditive. De plus, la qualité de vie est souvent impactée par la présence d'un acouphène dérangeant. Les patients ont le choix de s'adapter à la situation sans traitement ou de reconstituer une pseudo-stéréophonie à l'aide d'un appareillage qui transmet l'information auditive arrivant sur l'oreille sourde à l'oreille saine (Contralateral Routing of Signals (CROS)). L'implant cochléaire est une alternative récente qui permet de « réactiver ¼ l'oreille atteinte et de redonner ainsi une audition binaurale. Les différentes options de réhabilitation auditive en cas de surdité unilatérale en mettant l'accent sur l'implant cochléaire sont discutées à l'aide d'un cas clinique.

Characterization of a Structural Leoligin Analog as Farnesoid X Receptor Agonist and Modulator of Cholesterol Transport.

The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 µM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/ß, and peroxisome proliferator-activated receptors ß/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.

Intratemporal facial nerve schwannomas: multicenter experience of 80 cases.

PURPOSE: To provide more data on the clinical presentation and natural evolution of facial nerve schwannomas and to provide guidance for therapeutic decision making. METHODS: A retrospective case review of eighty patients diagnosed with a facial nerve schwannoma between 1990 and 2018 in ten tertiary referral centers in Europe was performed. Patients' demographics, symptomatology, audiometry, anatomical site (segments involved), size and whenever possible volume measurement were registered. RESULTS: At presentation, transient or persistent facial palsy was the most common symptom, followed by hearing loss. The schwannoma involved more than one segment in the majority of the patients with the geniculate ganglion being most commonly involved. Initial treatment consisted of a wait and scan approach in 67.5%, surgery in 30% and radiation therapy in 2.5% of the patients. Tympanic segment schwannomas caused mainly conductive hearing loss and were more prone to develop facial palsy at follow-up. Internal auditory canal or cerebellopontine angle schwannomas presented with significantly more sensorineural hearing loss. CONCLUSIONS: Although modern imaging has improved diagnosis of this tumor, choosing the best treatment modality remains a real challenge. Based on the literature review and current findings, more insights into the clinical course and the management of facial nerve schwannomas are provided.

Design and Synthesis of a Compound Library Exploiting 5-Methoxyleoligin as Potential Cholesterol Efflux Promoter.

5-Methoxyleoligin and leoligin are natural occurring lignans derived from Edelweiss (Leontopodium nivale ssp. alpinum), displaying potent pro-angiogenic and pro-arteriogenic activity. Cholesterol efflux from macrophages is associated with reverse cholesterol transport which inhibits the development of cardiovascular disease. Within this study, we developed a modular and stereoselective total synthesis of 5-methoxyleoligin which can be readily used to prepare a novel compound library of related analogs. The target 5-methoxyleoligin was synthesized exploiting a recently disclosed modular route, which allows also rapid synthesis of analogous compounds. All obtained products were tested towards macrophage cholesterol efflux enhancement and the performance was compared to the parent compound leoligin. It was found that variation on the aryl moiety in 2-position of the furan ring allows optimization of the activity profile, whereas the ester-functionality does not tolerate significant alterations.

Eight Items to Check on a Temporal Bone CT-Scan.

Imaging data provided by computed tomography scans of the temporal bone are fundamental for both the diagnosis and treatment of diseases affecting this complex structure. Despite its importance, the expertise required to analyze this exam is seldom properly acquired as it is time-consuming and often neglected among young doctors and even otolaryngologists. Physicians may not even have a look at the scans but rely only on radiology reports. Radiologists, on the other hand, may not describe the individual scans the same way as clinicians. Lack of a standardized and didactic protocol for scrolling through the images obtained might also contribute to the difficulties reported by residents and physicians in daily practice. We present here a sequential checklist which could be employed in a systematic and organized manner, aiming to both develop and practice the know-how of this indispensable and challenging method of evaluation of the temporal bone.

[Hypothyreosis after Hemithyroidectomy - surprisingly frequent complication in aftercare]. / Hypothyreose nach Hemithyreoidektomie − überraschend häufige Komplikation während der Nachsorge.

BACKGROUND: Hemithyroidectomy is a frequent treatment for thyroid nodules. Postoperative hypothyroidism is an often underestimated complication. We studied the incidence, time, symptoms and risk factors of postoperative hypothyroidism. MATERIAL AND METHODS: 127 Patients were analyzed in a retrospective chart review and with a structured assessment of the general practitioners and endocrinologists. Patients were classified according to the postoperative TSH as hypothyroid (>4.0 mU/L) or euthyroid (0.4-4.0 mU/L). Thyroid hormone was assessed at 4-6 Weeks, 6 months and 1 year. RESULTS: 55 patients (43 %) had postoperative hypothyroidism and 72 (57%) stayed euthyroid during follow up. The hypothyroidism occured during the first 2 months in 39 patients (71 %), between 2-6 months in 13 patients (24 %) and between 6-12 months in 3 patients (5 %). 33 patients (60 %) with hypothyroidism were asymptomatic and 16 patients (29 %) had symptoms. Preoperative TSH level was significantly higher in the hypothyroid group (1.64) compared to the euthyroid group (1.13, P = 0.0017). The other variables as age, gender, preoperative levels of T3, T4, Calcium and PTH showed no significant difference. CONCLUSION: Postoperative hypothyroidism is an important complication after hemithyroidectomy which should not be missed. Preoperative elevated TSH level is a riskfactor for postoperative hypothyroidism. All Patients after hemithyroidectomy should have postoperative TSH assessment after 4-6 weeks, 6 months and 12 months.

Titanium incus interposition ossiculoplasty: audiological outcomes and extrusion rates.

This study aimed to evaluate the benefit but also the extrusions, dislocations, and failures of a titanium incus prosthesis along with the long-term audiological outcomes. We prospectively collected data from 139 patients undergoing ossiculoplasty using the Fisch titanium incus prosthesis between 2001 and 2016. Overall, 126 patients with at least 6 months of follow-up (mean 4.5 years, range 6-155 months) were analyzed. Patients were grouped as "extrusion" (n = 9, 7%) if the prosthesis extruded, "failure" (n = 22, 18%) if a reoperation was needed concerning the prosthesis, and "stable" (n = 95, 75%) if the prosthesis remained functional in the middle ear. Mean postoperative air bone gaps (ABG) for 0.5-3 kHz for the overall group and the stable group were 19.8 (±11.9) and 15.3 (±7.5), respectively. Long-term results of stable group revealed an ABG (0.5-3 kHz) below 10 dB in 25% and below 20 dB in 81% of the patients. Atelectasis was the most frequent cause of extrusion, which occurred after a mean time of 28.7 months (range 15-48 months). Mean timing for reoperation was 30.7 months (range 5-131 months) in the failure group. There was no significant difference in mean postoperative ABG among patients with or without cholesteatoma, primary or staged ossiculoplasty in cholesteatoma, presence or absence of malleus head at the time of ossiculoplasty, open or closed cavity surgeries, or the degree of pneumatization of the temporal bone. The Fisch titanium incus prosthesis is a reliable alternative to using autologous incus for interposition ossiculoplasty, with similar hearing outcomes. Using this prosthesis, a 15 dB ABG should be expected.

[Benefit of Bimodal Stimulation with Cochlear Implant and Hearing Aid in Elderly Patients]. / Cochlea-Implantation ab dem 70. Lebensjahr ­ Nutzen der bimodalen Versorgung mit Hörgerät und CI.

Cochlear implant (CI) surgery is the standard of care for postlingual deafness in adults. A hearing aid (HA) for the non-implanted ear is normally used if residual hearing is available. There is limited data on bimodal stimulation in elderly patients. We compare the outcome of bimodal stimulation and analyzed the correlation of bimodal benefit and residual hearing in elderly patients. 22 patients≥70 years were implanted with a single-sided CI from 2002 till 2014. 17 patients use a HA on the non-implanted ear (bimodal). In a retrospective chart review we analyzed the audiological benefit (pure tone average, speech recognition). Time to follow-up was 6 month to 12 years. The subjective benefit was assessed using a structured questionnaire. The speech recognition (monosyllabic word testing in quiet @ 65 dB SPL) showed a score of 61% in bimodal condition vs. 53% with CI alone (p=0.35). There was no statistically significant correlation between residual hearing in the lower frequencies (250 Hz, 500 Hz and 1 kHz) and bimodal benefit. Most elderly patients benefit from bimodal stimulation. In quiet and in comparison with CI alone, most patients showed some improvement in word recognition scores using bimodal fitting, and all of them were using the contralateral hearing aid all day long. Postlingual deafened elderly patients fitted with a unilateral CI require a short rehabilitation period. In case of contralateral hearing aid fitting, regular control of the hearing aid should not be overlooked.

Leoligin, the Major Lignan from Edelweiss (Leontopodium nivale subsp. alpinum), Promotes Cholesterol Efflux from THP-1 Macrophages.

Leoligin is a natural lignan found in Edelweiss (Leontopodium nivale ssp. alpinum). The aim of this study was to examine its influence on cholesterol efflux and to address the underlying mechanism of action. Leoligin increases apo A1- as well as 1% human plasma-mediated cholesterol efflux in THP-1 macrophages without affecting cell viability as determined by resazurin conversion. Western blot analysis revealed that the protein levels of the cholesterol efflux transporters ABCA1 and ABCG1 were upregulated, whereas the SR-B1 protein level remained unchanged upon treatment with leoligin (10 µM, 24 h). Quantitative reverse transcription PCR further uncovered that leoligin also increased ABCA1 and ABCG1 mRNA levels without affecting the half-life of the two mRNAs in the presence of actinomycin D, a transcription inhibitor. Proteome analysis revealed the modulation of protein expression fingerprint in the presence of leoligin. Taken together, these results suggest that leoligin induces cholesterol efflux in THP-1-derived macrophages by upregulating ABCA1 and ABCG1 expression. This novel activity suggests leoligin as a promising candidate for further studies addressing a possible preventive or therapeutic application in the context of atherosclerosis.

The use of subtotal petrosectomy in cochlear implant candidates with chronic otitis media.

Cochlear implants (CI) candidates with chronic otitis media require special attention and management. The need of opening of the inner ear creates potential routes of spread of infection to subarachnoid spaces and lead to meningitis. The aim of the study was to analyse the technique and complications of subtotal petrosectomy (SP) in cochlear implant candidates with chronic otitis media at three different CI centres. A retrospective study was carried out in three Territory Referral Hospitals. The centres follow Fisch's philosophy and surgical techniques of SP. The study group consisted of 19 patients, 4 men and 15 women, aged 12-82 years. All patients underwent SP with either primary or staged CI implantation. Indications for single or a staged management, difficulties during surgery and complications were analysed. Skin and muscle flap design in primary and revision cases as well as imaging follow-up strategy are discussed. In 14 patients implantation was performed in a single stage and in 5 cases in two stages. Follow-up ranged from 8 months to 10 years. All the patients use their implants and there were no major nor minor complications. The use of subtotal petrosectomy with cochlear implants is a safe and efficient technique when strict surgical steps and rules are applied. Closure of the external ear canal after previous meatoplasty can be challenging and extreme care dissecting the skin flaps is required. In patients with extensive cholesteatoma, active discharge from the ear with resistant bacteria or an "unstable" situation, the procedure can be staged.

Fluoro- and perfluoralkylsulfonylpentafluoroanilides: synthesis and characterization of NH acids for weakly coordinating anions and their gas-phase and solution acidities.

Fluoro- and perfluoralkylsulfonyl pentafluoroanilides [HN(C6F5)(SO2X); X = F, CF3, C4F9, C8F17] are a class of imides with two different strongly electron-withdrawing substituents attached to a nitrogen atom. They are NH acids, the unsymmetrical hybrids of the well-known symmetrical bissulfonylimides and bispentafluorophenylamine. The syntheses, the structures of these perfluoroanilides, their solvates, and some selected lithium salts give rise to a structural variety beyond the symmetrical parent compounds. The acidities of representative subsets of these novel NH acids have been investigated experimentally and quantum-chemically and their gas-phase acidities (GAs) are reported, as well as the pKa values of these compounds in acetonitrile (MeCN) and DMSO solution. In quantum chemical investigations with the vertical and relaxed COSMO cluster-continuum models (vCCC/rCCC), the unusual situation is encountered that the DMSO-solvated acid Me2SO-H-N(SO2CF3)2, optimized in the gas phase (vCCC model), dissociates to Me2SO-H(+)-N(SO2CF3)2(-) during structural relaxation and full optimization with the solvation model turned on (rCCC model). This proton transfer underlines the extremely high acidity of HN(SO2CF3)2. The importance of this effect is studied computationally in DMSO and MeCN solution. Usually this effect is less pronounced in MeCN and is of higher importance in the more basic solvent DMSO. Nevertheless, the neglect of the structural relaxation upon solvation causes typical changes in the computational pKa values of 1 to 4 orders of magnitude (4-20 kJ mol(-1)). The results provide evidence that the published experimental DMSO pKa value of HN(SO2CF3)2 should rather be interpreted as the pKa of a Me2SO-H(+)-N(SO2CF3)2(-) contact ion pair.

Labyrinthine fenestration for stapes fixation in chronic ear disease others than otosclerosis.

The objective of this study is to assess the results of labyrinthine fenestration for fixed stapes in chronic ear disease. Using a prospective database, pre- and postoperative audiometric data from patients undergoing labyrinthine fenestration for fixation of the stapes in chronic ear disease others than otosclerosis between 2002 and 2012 were evaluated. Twenty-three labyrinthine fenestrations in chronic ear disease were performed (17 malleo-stapedotomies, 4 incus-stapedotomies, 1 neo-malleus-stapedotomy, 1 TORP-stapedotomy). Overall, the mean short-term (2 months) and long-term (42 months) postoperative air-bone gap (0.5-3 kHz) were 17.5 and 16.5 dB, respectively; long-term air-bone gap of <20 dB was obtained in 73 % of patients. There was no significant difference in air-bone gap closure between tympanosclerotic and post inflammatory osteogenic fixation of the stapes (p = 0.267). Hearing benefit success using the 'Belfast rule of the thumb' was achieved in 48 %. Normal bilateral hearing was achieved in 17 % and bilateral symmetric hearing impairment in 26 %. Only in 4 %, bone conduction worsened by more than 5 dB. Labyrinthine fenestration is an option in selected cases of stapes fixation in chronic ear disease and provides hearing gain without significant risk for sensorineural hearing loss. In those already selected cases, hearing benefit success 'Belfast rule of the thumb' is achieved only in half of the cases. This and the possible alternatives, should therefore be discussed preoperatively.

Surgical management of benign idiopathic osteonecrosis of the external auditory canal.

BACKGROUND/AIMS: Benign idiopathic osteonecrosis of the external ear canal remains a challenging management problem, with many patients experiencing a prolonged chronic course requiring frequent debridement. The technique of bony sequestrectomy, followed by rotation of a vascularized fascial flap and then a free full-thickness skin graft is presented. METHODS: Success with this technique is described in a retrospective case series format in addition to a review of the existing literature on surgical techniques for the treatment of this condition. RESULTS: The described technique was performed on 5 patients following prolonged periods of failed medical therapy (minimum 8 months). All 5 patients achieved a healed external auditory canal, with no ongoing skin ulceration or bony sequestration. Follow-up data (median 22 months) suggests that the technique provides a robust and long-lasting therapy. CONCLUSION: Symptomatic benign idiopathic osteonecrosis of the tympanic bone is well treated by provision of vascularized tissue to maximize the chance of bone healing and subsequent cure. It should be considered early in the management protocol to avoid lengthy symptomatic periods, the symptoms of which ultimately may not heal with medical therapy alone.

Combining bioengineered human skin with bioprinted cartilage for ear reconstruction.

Microtia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient's vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction.

Mucoepidermoid carcinoma of the parotid infiltrating the chorda tympani nerve.

We present here the first case report of a mucoepidermoid carcinoma of the parotid infiltrating the chorda tympani nerve and also discuss why an initial diagnosis of Bell palsy may be misleading.

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.