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.

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.

[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.

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.

[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.

Middle Cranial Fossa Approach: The Incudomalleolar Joint as a Reliable Landmark

Abstract Introduction The middle cranial fossa approach is performed by fewer neurotologists owing to a reduced number of indications. Consistent landmarks are mandatory to guide the surgeon in a narrow field. Objectives We have evaluated the incus and malleus head and the incudomalleal joint (IMJ) as a key landmark for identifying the superior semicircular canal (SSC) and to get oriented along the floor of the middle cranial fossa. Methods A combination of 20 temporal bone dissections and CT imaging were utilized to test and describe these landmarks. Results The blue line of the SSC is consistently identified along the prolongation of a virtual line through the IMJ and the angulation toward the root of zygoma. The mean distance from the zygoma toward the IMJ ranged from 1.60 to 1.90cm. Once the IMJ was identified, the blue line of the SSC was consistently found along the virtual line through the IMJ within 5 to 9mm. Conclusions The IMJ is a safe and consistent anatomical marker in the surgical approach to the middle cranial fossa floor. Opening the tegmen 1.5 to 2cm medial to the root of the zygoma and identifying the joint allows to trace a virtual line toward the SSC within 5 to 9mm. Knowledge of the close relationship between the direction of the IMJ and the superior canal can be used in all transtemporal approaches, thus orienting the surgeon in a rather narrow field with limited retraction of the dura and brain.

Middle Cranial Fossa Approach: The Incudomalleolar Joint as a Reliable Landmark.

Introduction The middle cranial fossa approach is performed by fewer neurotologists owing to a reduced number of indications. Consistent landmarks are mandatory to guide the surgeon in a narrow field. Objectives We have evaluated the incus and malleus head and the incudomalleal joint (IMJ) as a key landmark for identifying the superior semicircular canal (SSC) and to get oriented along the floor of the middle cranial fossa. Methods A combination of 20 temporal bone dissections and CT imaging were utilized to test and describe these landmarks. Results The blue line of the SSC is consistently identified along the prolongation of a virtual line through the IMJ and the angulation toward the root of zygoma. The mean distance from the zygoma toward the IMJ ranged from 1.60 to 1.90cm. Once the IMJ was identified, the blue line of the SSC was consistently found along the virtual line through the IMJ within 5 to 9mm. Conclusions The IMJ is a safe and consistent anatomical marker in the surgical approach to the middle cranial fossa floor. Opening the tegmen 1.5 to 2cm medial to the root of the zygoma and identifying the joint allows to trace a virtual line toward the SSC within 5 to 9mm. Knowledge of the close relationship between the direction of the IMJ and the superior canal can be used in all transtemporal approaches, thus orienting the surgeon in a rather narrow field with limited retraction of the dura and brain.

Tympanoplasty with an Intact Stapes Superstructure in Chronic Otitis Media.

BACKGROUND: The objective of our study was to ascertain the functional results in terms of air bone gap (ABG) closure over 4 frequencies (0.5, 1, 2, 3 kHz) in patients with chronic otitis media (COM) that underwent tympanoplasty in the presence of a mobile stapes superstructure, and in particular excluding those cases in which the malleus was used in the reconstruction. METHODS: A retrospective review of our database between January 1, 2006 and June 1, 2018 identified all cases that underwent one of 3 reconstructive options: the classic Type III tympanoplasty in an open-cavity setting; the "stapes augmentation" (SA) type reconstruction where the stapes superstructure is augmented to the drum by an interposing partial ossiculoplasty of either autologous bone, cartilage, or prosthetic material; and the use of a total articular replacement prosthesis (TORP) from the stapes footplate to the drum in the presence of an intact superstructure. RESULTS: A total of 116 procedures in 112 patients were identified with a mean ABG reduction from 27 dB to 21 dB (P < .05). There was no significant difference in the mean post-operative ABG result between Type III (19.21 dB), TORP+ (24.90 dB), or SA (20.94 dB) reconstructions (P = .368). Overall, an ABG ≤ 20 dB or "surgical success" was achieved in 56% (n = 65) of cases. Only 20% (n = 23) of cases had "failure" or a post-operative ABG >30 dB. CONCLUSION: Tympanoplasty with an intact stapes superstructure in COM is expected to provide acceptable levels of surgical success. We did not identify any particular risk factors associated with improved outcome.

Audiological Outcome in Myringoplasties with an Intact Ossicular Chain: Is there a Difference between Chronic Otitis with or without Cholesteatoma?

Introduction Chronic otitis media (COM) with a central perforation or a concomitant cholesteatoma are both inflammatory lesions, however, with different etiologies. Both entities may present with an intact chain, and the final reconstruction is quite similar. Does it also apply for the hearing outcome? Objectives In a retrospective analysis, we investigated the preoperative hearing and the final hearing outcome of two groups of patients: those with COM and those with cholesteatoma, and compared various factors. Methods Patients operated between 2010 and 2019 were entered prospectively into a research database, and the integrity of the ossicular chain, the extent of the cholesteatoma, and the findings on computed tomography (CT) scans were retrospectively analyzed and correlated to the final hearing outcome. Results Out of 210 tympanoplasties for COM, 162 (80%) presented with an intact chain, and 85 (40%) ears could be analyzed. Out of 283 cholesteatoma surgeries, 53 (19%) ears presented with an intact chain. The preoperative air-bone gap (ABG) was worse in the COM group, but the postoperative ABG over the frequencies of 0.5 kHz and 4 kHz was the same (10 dB to 12 dB) in both groups, and remained within 20 dB in 90% (40 and 78 patients, respectively). The extension of the disease was rather limited in the cholesteatoma group (stages Ch1a and 1b), and better pneumatization and ventilation were beneficial for a good result. Postoperatively, the frequency of 4 kHz had the largest ABG (14 dB and 18 dB). Conclusion Overall, 80% of the patients with COM and less than 20% of those with cholesteatoma had an intact and mobile chain at surgery. Using equivalent surgical techniques for the tympanoplasty, the final outcome was almost the same for both groups, with a mean ABG of 10 dB to 12 dB.

Audiological Outcome in Myringoplasties with an Intact Ossicular Chain: Is there a Difference between Chronic Otitis with or without Cholesteatoma?

Abstract Introduction Chronic otitis media (COM) with a central perforation or a concomitant cholesteatoma are both inflammatory lesions, however, with different etiologies. Both entities may present with an intact chain, and the final reconstruction is quite similar. Does it also apply for the hearing outcome? Objectives In a retrospective analysis, we investigated the preoperative hearing and the final hearing outcome of two groups of patients: those with COM and those with cholesteatoma, and compared various factors. Methods Patients operated between 2010 and 2019 were entered prospectively into a research database, and the integrity of the ossicular chain, the extent of the cholesteatoma, and the findings on computed tomography (CT) scans were retrospectively analyzed and correlated to the final hearing outcome. Results Out of 210 tympanoplasties for COM, 162 (80%) presented with an intact chain, and 85 (40%) ears could be analyzed. Out of 283 cholesteatoma surgeries, 53 (19%) ears presented with an intact chain. The preoperative air-bone gap (ABG) was worse in the COM group, but the postoperative ABG over the frequencies of 0.5 kHz and 4 kHz was the same (10 dB to 12 dB) in both groups, and remained within 20 dB in 90% (40 and 78 patients, respectively). The extension of the disease was rather limited in the cholesteatoma group (stages Ch1a and 1b), and better pneumatization and ventilation were beneficial for a good result. Postoperatively, the frequency of 4 kHz had the largest ABG (14 dB and 18 dB). Conclusion Overall, 80% of the patients with COM and less than 20% of those with cholesteatoma had an intact and mobile chain at surgery. Using equivalent surgical techniques for the tympanoplasty, the final outcome was almost the same for both groups, with a mean ABG of 10 dB to 12 dB.

Investigation of Leoligin Derivatives as NF-κΒ Inhibitory Agents.

The transcription factor NF-κB is an essential mediator of inflammation; thus, the identification of compounds that interfere with the NF-κB signaling pathway is an important topic. The natural products leoligin and 5-methoxyleoligin have served as a starting point for the development of NF-κB inhibitors. Using our modular total synthesis method of leoligin, modifications at two positions were undertaken and the effects of these modifications on the biological activity were investigated. The first modification concerned the ester functionality, where it was found that variations in this position have a significant influence, with bulky esters lacking Michael-acceptor properties being favored. Additionally, the substituents on the aryl group in position 2 of the tetrahydrofuran scaffold can vary to some extent, where it was found that a 3,4-dimethoxy and a 4-fluoro substitution pattern show comparable inhibitory efficiency.

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.

[The comparison of malleostapedotomy in primary and revision stapes surgery for otosclerosis].

Objective: To compare the effectiveness of primary malleostapedotomy with revision malleostapedotomy for otosclerosis. Methods: From April 2002 to December 2017, 70 consecutive patients with otosclerosis who underwent malleostapedotomy were reviewed. Depending on the primary malleostapedotomy (P-MS) or revision malleostapedotomy (R-MS), the patients were divided into P-MS group or R-MS group.The intraoperative findings and hearing results before and after surgery were compared between the two groups. ALL data were analyzed using SPSS 23. Results: Totally 73 malleostapedotomy were performed in 73 ears of 70 patients, including 38 P-MS and 35 R-MS. There was no significant difference between the two groups in sex ratio, age and operated ears (P>0.05 for all). The most common finding at P-MS was incus fixation (50.0%, 19/38) versus prosthesis displacement for R-MS (60.0%, 21/35) . Overall, the air-bone gap (ABG) improvement in P-MS were (18.1±8.2) dB in 0.5-3 kHz and (18.3±8.5) dB in 0.5-4 kHz, without significant difference to those in R-MS (P>0.05) . 31.4% of R-MS in 0.5-3 kHz and 22.9% R-MS in 0.5-4 kHz achieved an ABG<10 dB, significantly lower than those of P-MS (65.8% in 0.5-3 kHz and 57.9% in 0.5-4kHz; P<0.05). Failure (postoperative ABG>30 dB) occurred in 11.4% in R-MS and 0 in P-MS (for 0.5-3 kHz and 0.5-4 kHz). The incidence of postoperative sensorineural hearing loss (>10 dB increase in bone conduct) in R-MS group was 8.6% in 0.5-3 kHz and 0.5-4 kHz, without significant difference to those in P-MS (P>0.05) . 80.0% (20/25) of first R-MS achieved ABG<20 dB, compared to 37.5% (3/8) of second R-MS with ABG<20 dB. Conclusions: Although both P-MS and R-MS can significantly improve hearing, with similar risk of inner ear damage, R-MS is less effective and poses a higher risk of failure than P-MS. For patients with insufficient hearing improvement after first R-MS, conventional hearing aids or implantable hearing devices may be considered as an alternative.

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.

Multicenter Study Investigating Foreign Language Acquisition at School in Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants in the Swiss German Population.

OBJECTIVES: Evaluation of foreign language acquisition at school in cochlear implant patients. STUDY DESIGN: Multicenter cohort study. SETTING: CI centers. PATIENTS: One hundred twenty-five CI users (10-18 yr) in the German-speaking part of Switzerland were enrolled. Demographic data were obtained by means of written questionnaires. German-speaking children with mainstream foreign language tuition (English and/or French) were enrolled for further testing. The control group of normal-hearing individuals was matched on age, class, and number of foreign language lessons attended. RESULTS: Overall, 100 questionnaires were returned. The 12 CI users without foreign language learning attended special schools. CI users who attended foreign language classes had better German speech comprehension compared with those without foreign language tuition (89 versus 51%; p < 0.05). Thirty-one CI users of different grades were further tested. All (10/10) CI 6th graders attained the school objectives for both English reading and listening skills. French performance at 6th grade for reading was 3/7 and for listening only 1/7. There were 13 matched normal-hearing pairs for English and 10 for French. The total scores were on average 7% higher, with a statistical significance for English reading (p < 0.05). CONCLUSIONS: Almost 90% of CI children in Switzerland learn foreign language(s) at school. All the tested patients reached the current school objectives for English reading. The success rate for French was lower, especially regarding listening tasks. The 13 matched pairs with normal-hearing did not score substantially better.

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.

Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease.

Recently, a natural compound leoligin, a furan-type lignan, was discovered as an interesting hit compound with an anti-inflammatory pharmacological activity profile. We developed a modular and stereoselective approach for the synthesis of the edelweiss-derived lignan leoligin and used the synthetic route to rapidly prepare leoligin analogs even on the gram scale. Proof of concept of this approach together with cell-based bio-assays gained structural analogs with increased selectivity towards vascular smooth muscle versus endothelial cell proliferation inhibition, a major benefit in fighting vascular neointima formation. In addition, we identified the structural features of leoligin analogs that define their ability to inhibit the pro-inflammatory NF-κB pathway. Results are discussed in the context of structural modification of these novel synthetic lignans.

Introducing the "ChOLE" Classification and Its Comparison to the EAONO/JOS Consensus Classification for Cholesteatoma Staging.

: Many previous attempts have been made to classify or categorize cholesteatomas. Recently, the European Academy of Otology and Neurotology and the Japanese Otological Society proposed a classification system based primarily on extension and complications. The European Academy of Otology and Neurotology/Japanese Otological Society consensus statement makes an effort to standardize reporting of surgical techniques. Internet-based multicenter studies are facilitated by increasing connectivity, but a mutually-agreed framework for reporting is necessary for results to be comparable across sites. New technologies compete with established standardized surgical approaches and need to be validated. It is definitively the right time to find a consensus on how to record and report surgical findings in cholesteatoma surgery. To stimulate this interesting discussion, we propose a ChOLE-classification system, which is based on the differentiation into extension (Ch), status of the ossicular chain at the end of surgery (O), complications (L), and degree of pneumatization and ventilation (E). A numeric rule is used to stage these cholesteatomas from I-III.