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Purpose: To study outcome after cochlear implantation using the Cochlear Implant (CI) outcome assessment protocol based on the International Classification of Functioning, Disability and Health (ICF) model (CI-ICF)., Methods: Raw data of a prospective, longitudinal, multicenter study was analyzed. Seventy-two CI candidates were assessed preoperatively and six months postoperatively using the CI-ICF protocol. Following tools were used: (1) Work Rehabilitation Questionnaire (WORQ), (2) Abbreviated Profile of Hearing Aid Benefit (APHAB), (3) Audio Processor Satisfaction Questionnaire (APSQ), (4) Speech, Spatial, and Qualities of Hearing Scale (SSQ12), (5) Hearing Implant Sound Quality Index (HISQUI19), (6) Nijmegen CI Questionnaire (NCIQ) (7) pure tone audiometry, (8) speech audiometry, (9) sound localization., Results: There was a significant improvement of speech discrimination in quiet (p = 0.015; p < 0.001) and in noise (p = 0.041; p < 0.001), sound detection (p < 0.001), tinnitus (p = 0.026), listening (p < 0.001), communicating with-receiving-spoken messages (p < 0.001), conversation (p < 0.001), family relationships (p < 0.001), community life (p = 0.019), NCIQ total score and all subdomain scores (p < 0.001). Subjective sound localization significantly improved (p < 0.001), while psychometric sound localization did not. There was no significant subjective deterioration of vestibular functioning and no substantial change in sound aversiveness. CI users reported a high level of implant satisfaction postoperatively., Conclusion: This study highlights the positive impact of cochlear implantation on auditory performance, communication, and subjective well-being. The CI-ICF protocol provides a holistic and comprehensive view of the evolution of CI outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Cochlear duct length (CDL) measurement plays a role in the context of individualized cochlear implant (CI) surgery regarding an individualized selection and implantation of the CI electrode carrier and an efficient postoperative anatomy-based fitting process. The level of detail of the preoperative temporal bone CT scan depends on the imaging modality with major impact on CDL measurements and CI electrode contact position determination. The aim of this study was to evaluate the accuracy of perioperative CDL measurements and electrode contact determination in photon-counting CT (PCCT)., Methods: Ten human fresh-frozen petrous bone specimens were examined with a first-generation PCCT. A clinically applicable radiation dose of 27.1 mGy was used. Scans were acquired before and after CI insertion. Postoperative measurement of the CDL was conducted using an otological planning software and 3D-curved multiplanar reconstruction. Investigation of electrode contact position was performed by two respective observers. Measurements were compared with a conventional multislice CT and to a high-resolution flat-panel volume CT with secondary reconstructions., Results: Pre- and postoperative CDL measurements in PCCT images showed no significant difference to high-resolution flat-panel volume CT. Postoperative CI electrode contact determination was also as precise as the flat-panel CT-based assessment. PCCT and flat-panel volume CT were equivalent concerning interobserver variability., Conclusion: CDL measurement with PCCT was equivalent to flat-panel volume CT with secondary reconstructions. PCCT enabled highly precise postoperative CI electrode contact determination with substantial advantages over conventional multislice CT scanners., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

α-solanine is a glycoalkaloid that is commonly found in nightshades ( Solanum ) and has a toxic effect on the human organism. Among other things, it is already known to inhibit tumor cell proliferation and induce apoptosis in tumor cell lines. Due to its potential as a tumor therapeutic, the current study investigated the effect of α-solanine on head and neck squamous cell carcinoma (HNSCC). In addition, genotoxic and antiangiogenic effects on human umbilical vein endothelial cells (HUVECs) were evaluated at subtoxic α-solanine concentrations. Cytotoxicity and apoptosis rates were measured in two human HNSCC cell lines (FaDu pharynx carcinoma cells and CAL-33 tongue carcinoma cells), as well as in HUVECs. MTT and Annexin V analyses were performed 24 h after α-solanine treatment at increasing doses up to 30 µM to determine cytotoxic concentrations. Furthermore, genotoxicity at subtoxic concentrations of 1, 2, 4 and 6 µM in HUVECs was analyzed using single-cell gel electrophoresis (comet assay). The antiangiogenic effect on HUVECs was evaluated in the capillary tube formation assay. The MTT assay indicated an induction of concentration-dependent viability loss in FaDu and CAL-33 cancer cell lines, whereas the Annexin V test revealed α-solanine-induced cell death predominantly independent from apoptosis. In HUVECs, the cytotoxic effect occurred at lower concentrations. No genotoxicity or inhibition of angiogenesis were detected at subtoxic doses in HUVECs. In summary, α-solanine had a cytotoxic effect on both malignant and non-malignant cells, but this was only observed at higher concentrations in malignant cells. In contrast to existing data in the literature, tumor cell apoptosis was less evident than necrosis. The lack of genotoxicity and antiangiogenic effects in the subtoxic range in benign cells are promising, as this is favorable for potential therapeutic applications. In conclusion, however, the cytotoxicity in non-malignant cells remains a severe hindrance for the application of α-solanine as a therapeutic tumor agent in humans., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Von Fournier et al.)

Background: The size of the human cochlear, measured by the diameter of the basal turn, varies between 7 and 11 mm. For hearing rehabilitation with cochlear implants (CI), the size of the cochlear influences the individual frequency map and the choice of electrode length. OTOPLAN® (CAScination AG [Bern, Switzerland] in cooperation with MED-EL [Innsbruck, Austria]) is a software tool with CE marking for clinical applications in CI treatment which allows for precise pre-planning based on cochlear size. This literature review aims to analyze all published data on the application of OTOPLAN®., Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to identify relevant studies published in the PubMed search engine between January 2015 and February 2023 using the search terms "otoplan" [title/abstract] OR "anatomy-based fitting" [title/abstract] OR "otological software tool" [title/abstract] OR "computed tomography-based software AND cochlear" [title/abstract]., Results: The systematic review of the literature identified 32 studies on clinical use of OTOPLAN® in CI treatment. Most studies were reported from Germany (7 out of 32), followed by Italy (5), Saudi Arabia (4), the USA (4), and Belgium (3); 2 studies each were from Austria and China, and 1 study from France, India, Norway, South Korea, and Switzerland. In the majority of studies (22), OTOPLAN® was used to assess cochlear size, followed by visualizing the electrode position using postoperative images (5), three-dimensional segmentation of temporal bone structures (4), planning the electrode insertion trajectory (3), creating a patient-specific frequency map (3), planning of a safe drilling path through the facial recess (3), and measuring of temporal bone structures (1)., Conclusion: To date, OTOPLAN® is the only DICOM viewer with CE marking in the CI field that can process pre-, intra-, and postoperative images in the abovementioned applications., (© 2024. The Author(s).)

Objective: Education in microsurgery of the ear includes staged training to allow for mastering of the complex microsurgical procedures, particularly in the context of middle ear reconstruction and cochlear implantation. Traditional surgical training includes temporal bone preparations by cadaver dissection and supervised operating room practice. As these on-site trainings are limited, there is a need to broaden education facilities in an on-line format. Therefore, a first basic on-line training for otosurgery was developed., Materials and Methods: The system consists of an artificial temporal bone model together with a set of basic surgical instruments and implant dummies. As an essential part of the training kit, a high-resolution camera set is included that allows for connection to a video streaming platform and enables remote supervision of the trainees' surgical steps by experienced otological surgeons. In addition, a pre-learning platform covering temporal bone anatomy and instrumentation and pre-recorded lectures and instructional videos has been developed to allow trainees to review and reinforce their understanding before hands-on practice., Results: Over the three courses held to date, 28 participants with varying levels of prior surgical experience took part in this otological surgical training program. The immediate feedback of the participants was evaluated by means of a questionnaire. On this basis, the high value of the program became apparent and specific areas could by identified where further refinements could lead to an even more robust training experience., Conclusion: The presented program of an otosurgical online training allows for basal education in practical exercises on a remote system. In this way, trainees who have no direct access to on-site instruction facilities in ear surgery now have the chance to start their otosurgical training in an educational setting adapted to modern technologies., (© 2024. The Author(s).)

Background: In patients with iodine-negative thyroid cancer (TC), current guidelines endorse an [ 18 F]FDG PET/CT to identify dedifferentiated sites of disease. We aimed to determine the rate of oncological management changes triggered by such a molecular imaging approach, along with the impact on outcome., Methods: 42 consecutive patients with negative findings on [ 131 I] whole body scan were scheduled for [ 18 F]FDG PET/CT and treatment based on PET results were initiated. To determine the impact on oncological management, we compared the therapeutic plan prior to and after molecular imaging. Based on imaging follow-up, the rate of controlled disease (CD, defined as stable disease, complete or partial response) was also recorded, thereby allowing to assess whether [ 18 F]FDG-triggered management changes can also lead to favorable outcome., Results: We observed no alterations of the treatment plan in 9/42 (21.4%) subjects (active surveillance in 9/9 [100%]). Oncological management was changed in the remaining 33/42 (78.6%; systemic treatment in 9/33 [27.3%] and non-systemic treatment in 24/33 [72.7%]). Among patients receiving non-systemic therapy, the following changes were noted: surgery in 20/24 (83.3%) and radiation therapy in 4/24 (16.7%). In the systemic group, tyrosine kinase inhibitor (TKI) was prescribed in 8/9 (88.9%), while radioiodine therapy based on a TKI-mediated redifferentiation approach was conducted in 1/9 (11.1%). In 26 subjects with available follow-up, rate of CD was 22/26 (84.6%) and among those, 15/22 (68.1%) had experienced previous management changes based on PET/CT findings., Conclusions: In subjects with iodine-negative TC, [ 18 F]FDG PET/CT triggered relevant management changes along with disease control in the vast majority of patients. As such, in dedifferentiated TC, [ 18 F]FDG PET/CT may serve as a relevant management tool and therapeutic decision-aid in the clinic., (© 2023. The Author(s).)

Objective: Education in microsurgery of the ear includes staged training to allow for mastering of the complex microsurgical procedures, particularly in the context of middle ear reconstruction and cochlear implantation. Traditional surgical training includes temporal bone preparations by cadaver dissection and supervised operating room practice. As these on-site trainings are limited, there is a need to broaden education facilities in an on-line format. Therefore, a first basic on-line training for otosurgery was developed., Materials and Methods: The system consists of an artificial temporal bone model together with a set of basic surgical instruments and implant dummies. As an essential part of the training kit, a high-resolution camera set is included that allows for connection to a video streaming platform and enables remote supervision of the trainees' surgical steps by experienced otological surgeons. In addition, a pre-learning platform covering temporal bone anatomy and instrumentation and pre-recorded lectures and instructional videos has been developed to allow trainees to review and reinforce their understanding before hands-on practice., Results: Over the three courses held to date, 28 participants with varying levels of prior surgical experience took part in this otological surgical training program. The immediate feedback of the participants was evaluated by means of a questionnaire. On this basis, the high value of the program became apparent and specific areas could by identified where further refinements could lead to an even more robust training experience., Conclusion: The presented program of an otosurgical online training allows for basal education in practical exercises on a remote system. In this way, trainees who have no direct access to on-site instruction facilities in ear surgery now have the chance to start their otosurgical training in an educational setting adapted to modern technologies., (© 2024. The Author(s).)

Background: The size of the human cochlear, measured by the diameter of the basal turn, varies between 7 and 11 mm. For hearing rehabilitation with cochlear implants (CI), the size of the cochlear influences the individual frequency map and the choice of electrode length. OTOPLAN® (CAScination AG [Bern, Switzerland] in cooperation with MED-EL [Innsbruck, Austria]) is a software tool with CE marking for clinical applications in CI treatment which allows for precise pre-planning based on cochlear size. This literature review aims to analyze all published data on the application of OTOPLAN®., Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to identify relevant studies published in the PubMed search engine between January 2015 and February 2023 using the search terms "otoplan" [title/abstract] OR "anatomy-based fitting" [title/abstract] OR "otological software tool" [title/abstract] OR "computed tomography-based software AND cochlear" [title/abstract]., Results: The systematic review of the literature identified 32 studies on clinical use of OTOPLAN® in CI treatment. Most studies were reported from Germany (7 out of 32), followed by Italy (5), Saudi Arabia (4), the USA (4), and Belgium (3); 2 studies each were from Austria and China, and 1 study from France, India, Norway, South Korea, and Switzerland. In the majority of studies (22), OTOPLAN® was used to assess cochlear size, followed by visualizing the electrode position using postoperative images (5), three-dimensional segmentation of temporal bone structures (4), planning the electrode insertion trajectory (3), creating a patient-specific frequency map (3), planning of a safe drilling path through the facial recess (3), and measuring of temporal bone structures (1)., Conclusion: To date, OTOPLAN® is the only DICOM viewer with CE marking in the CI field that can process pre-, intra-, and postoperative images in the abovementioned applications., (© 2024. The Author(s).)

Introduction: The middle cranial fossa (MCF) approach is a well-established procedure in surgery of the internal auditory canal, as well as with the retrosigmoid and translabyrinthine approaches. It is commonly used in the hearing-preserving microsurgery of small vestibular schwannomas (VS). The debate about the "best" approach for the microsurgery of small VS without contact to the brainstem is controversial. It has been stated that the MCF approach leads to irreversible damage to the temporal lobe, which may be evident in follow-up magnet resonance imaging (MRI) as gliosis in up to 70% of patients., Materials and Methods: This study represents a retrospective chart analysis conducted at a tertiary university hospital. Here, 76 postoperative MRIs were re-evaluated by an experienced neuroradiologist and compared with the preoperative images. Temporal lobe gliosis was classified on an ordinal scale as absent, slight, moderate or severe. Occurrence of gliosis was matched to the clinical predictors (tumor stage, tumor volume, sex, age, and side)., Results: No case of severe or moderate gliosis was found in the patient group. Slight gliosis of the temporal lobe was rare and was only detected in four patients (5%). There was no relation between clinical predictors and the incidence of gliosis., Conclusions: In our cohort, postoperative MR imaging did not reveal relevant damage to the temporal lobe parenchyma. This confirms the safe concept of microsurgery of small tumors via the middle fossa approach. The severe glioses described in other studies may be caused by a forced insertion of the retractor or by more extended approaches. However, further prospective neurocognitive studies seem to be necessary in order to assess functional changes in the temporal lobe., Competing Interests: The authors declare no conflicts of interest.

Background: Correct individual tonotopic frequency stimulation of the cochlea plays an important role in the further development of anatomy based cochlear implantation. In this context frequency specific fitting of the basal electrode contact with a normal insertion depth can be difficult since it is often placed in a frequency range higher than 10 kHz and current audio processors only stimulate for frequencies up to 8.5 kHz due to microphone characteristics. This results in a mismatch of the high frequencies. Therefore, this study represents a proof of concept for a tonotopic correct insertion and aims to develop an algorithm for a placement of the basal electrode below 8.5 kHz in an experimental setting., Methods: Pre- and postoperative flat-panel volume CT scans with secondary reconstructions were performed in 10 human temporal bone specimens. The desired frequency location for the most basal electrode contact was set at 8.25 kHz. The distance from the round window to the position where the basal electrode contact was intended to be located was calculated preoperatively using 3D-curved multiplanar reconstruction and a newly developed mathematical approach. A specially designed cochlear implant electrode array with customized markers imprinted on the silicone of the electrode array was inserted in all specimens based on the individually calculated insertion depths. All postoperative measurements were additionally validated using an otological planning software., Results: Positioning of the basal electrode contact was reached with only a small mean deviation of 37 ± 399 Hz and 0.06 ± 0.37 mm from the planned frequency of 8.25 kHz. The mean rotation angle up to the basal electrode contact was 51 ± 5 °. In addition, the inserted electrode array adequately covered the apical regions of the cochleae., Conclusion: Using this algorithm, it was possible to position the basal electrode array contact in an area of the cochlea that could be correctly stimulated by the existing speech processors in the context of tonotopic correct fitting., (S. Karger AG, Basel.)

Background: German university otorhinolaryngology has a need for digital teaching content. Case-based e‑learning represents a digital teaching methodology. The data on student use of case-based e‑learning in university teaching of ENT medicine are limited., Objective: The aim of this work was to determine the extent to which voluntary case-based e‑learning is used by otolaryngology students and what influence the quality of the e‑learning has on motivation to use e‑learning and on the interest in otolaryngology., Materials and Methods: Fifteen voluntary e‑learning cases were created based on the content of the ENT lecture in the winter semester 2022/2023. Subsequently, a descriptive evaluation of the usage statistics of the cases of 157 students was conducted. Likewise, an evaluation of the quality of the e‑learning as well as the motivation to complete it and the interest in otorhinolaryngology was carried out using a voluntary questionnaire., Results: Voluntary case-based e‑learning was used to varying degrees by 66% of the students. The quality of e‑learning correlated significantly with the motivation and the interest in otolaryngology., Conclusion: The teaching content of otorhinolaryngology can be implemented sufficiently in case-based e‑learning and is characterized by satisfactory student acceptance. Integration should be accomplished in a high-quality manner to increase motivation and interest in otorhinolaryngology., (© 2024. The Author(s).)

Hypothesis: Measurements of the cochlear duct length (CDL) are dependent on the resolution of the imaging dataset., Background: Previous research has shown highly precise cochlear measurements using 3D-curved multiplanar reconstruction (MPR) and flat-panel volume computed tomography (fpVCT). Thus far, however, there has been no systematic evaluation of the imaging dataset resolution required for optimal CDL measurement. Therefore, the aim of this study was to evaluate the dependence of CDL measurement on the resolution of the imaging dataset to establish a benchmark for future CDL measurements., Methods: fpVCT scans of 10 human petrous bone specimens were performed. CDL was measured using 3D-curved MPR with secondary reconstruction of the fpVCT scans (fpVCT SECO ) and increasing resolution from 466 to 99 μm. In addition, intraobserver variability was evaluated. A best-fit function for calculation of the CDL was developed to provide a valid tool when there are no measurements done with high-resolution imaging datasets., Results: Comparison of different imaging resolution settings showed significant differences for CDL measurement in most of the tested groups ( p < 0.05), except for the two groups with the highest resolution. Imaging datasets with a resolution lower than 200 μm showed lower intraobserver variability than the other resolution settings, although there were no clinically unacceptable errors with respect to the Bland-Altman plots. The developed best-fit function showed high accuracy for CDL calculation using resolution imaging datasets of 300 μm or lower., Conclusion: 3D-curved MPR in fpVCT with a resolution of the imaging dataset of 200 μm or higher revealed the most precise CDL measurement. There was no benefit of using a resolution higher than 200 μm with regard to the accuracy of the CDL measurement., Competing Interests: Conflicts of interest and source of funding: none., (Copyright © 2024, Otology & Neurotology, Inc.)

In Germany, an increased volume of patient cases in the emergency department has been observed for several years, many of which do not represent hospital emergencies. To improve the triage and management of patient flows, the Structured Initial Medical Assessment (Strukturierte medizinische Ersteinschätzung in Deutschland, SmED) triage system was developed. This certified medical product is intended to assess both the urgency of everyday complaints and their adequate medical care in a targeted, faster, and safer manner. It supports medical professionals in triage by suggesting courses of action, whereby the ultimate responsibility remains with the professionals themselves. For otorhinolaryngology, a content review was carried out with regard to plausibility and patient safety in the head and neck region on the basis of nine specific emergencies. The cases were simulated by nine otorhinolaryngologists and triaged on the basis of the SmED by medical staff and medical students by assigning a care level and timepoint (urgency). The majority of cases were correctly assigned. The SmED initial assessment system is a good tool for assessing urgent clinical pictures in ear, nose, and throat (ENT) medicine. The long-term goal of the initial assessment is to relieve the capacities of outpatient departments. In order to achieve this and to shorten patient waiting times, it would be necessary to refer patients quickly to otorhinolaryngology. It is therefore necessary to ensure that patients are referred to an ENT on-call service via the online tool., (© 2024. The Author(s).)

Objective: Image enhancement systems are important diagnostic tools in the detection of laryngeal pathologies. This study aimed to compare three different image enhancement systems: professional image enhancement technology, Image1 S and narrow-band imaging., Method: Using the three systems, 100 patients with laryngeal lesions were investigated using a flexible and a 30° rigid endoscope. The lesions were diagnosed by three experts and classified using the Ni classification. The findings were compared., Results: Lesions classified as 'benign' were histopathologically confirmed in 50 per cent of patients, malignant lesions were confirmed in 41 per cent and recurrent respiratory papillomatosis were confirmed in 9 per cent. There was no significant difference between the experts' assessments of each image enhancement system., Conclusion: The three systems give comparable results in the detection of laryngeal lesions. With two additional systems, more users can perform image-enhanced endoscopy, resulting in a broadly available tool that can help to improve oncological assessment.

Introduction: In times of COVID-19, gargling disinfectant is commonly used. Disinfectant solutions seem to decrease the infection's symptoms. For disinfection, several techniques are reported. So far, there are no data about the regions in the upper airways achieved by gargled fluid., Methods: Ten healthy volunteers without any dysphagia were investigated with a high-sensitivity flexible endoscopic evaluation of swallowing (hsFEES®) during and after gargling colored water. One volunteer repeated the gargling process in fast and real-time MRI., Results: In all cases, no color accumulation was detected on the posterior pharyngeal wall, epi- or hypopharynx during gargling. The MRI scans confirmed the results., Conclusions: hsFEES® and fast MRI provide an insight into the gargling pattern. Data show that during gargling, the fluid covers the soft tissue in the oral cavity and the anterior part of the soft palate, but not the posterior pharyngeal wall nor the epi- and hypopharynx., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To investigate the surgical approach and the audiological outcome of a stapes head coupler in active middle ear implant surgery., Study Design: Retrospective data analysis., Setting: Tertiary referral center with a large active middle ear implant program., Patients: Twelve patients with active middle ear implant surgery., Interventions: Therapeutic surgical approach for hearing rehabilitation in human subjects., Main Outcome Measures: Auditory brainstem response, sound field thresholds, vibrogram, speech perception in the Freiburger monosyllabic word test., Results: The stapes head was attached safely in different coupling situations. Audiological outcomes were similar to the audiological performance of established vibroplasty couplers presented in the literature., Conclusion: The stapes head coupler is a new and safe tool for vibroplasty with a good audiological outcome., Competing Interests: Conflicts of interest: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Background: Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome., Methods: Treatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated., Results: Patients were IRS group II (n = 15) and III (n = 380) and received systemic treatment according to the enrolled protocols: I2VA (n = 172), VAIA/CEVAIE (n = 223). Delayed resection was performed in 88/395 (22%) patients, and RT was additionally given in 79/88 (90%) resected patients. RT was the predominant local treatment in 355/395 (90%) patients: hyperfractionated accelerated photon (HART; n = 77), conventionally fractionated photon (n = 91) or proton beam (n = 126), brachytherapy (n = 4), heavy ions (n = 1), not available (n = 56). In the subgroup of RT as only local treatment (n = 278), no intracranial tumor extension and complete remission at end of treatment were significant positive prognostic factors. No significant difference on tumor outcome was seen between different radiotherapy concepts. Long-term toxicity with mostly endocrinological and visual deficiencies was reported in 161/279 (58%) surviving patients with a lower trend after proton beam RT (48%) when compared to HART or conventionally fractionated photon RT (71% and 72%, respectively). Ten-year event-free and overall survival in the overall group were 62% (±5, 95% confidence interval [CI]) and 67% (±5, 95% CI); in the RT-only group 67% (±6, 95% CI) and 71% (±6, 95% CI), respectively., Conclusion: CWS data confirm the recent RT concept in PM RMS. Long-term sequelae as endocrinological and visual deficiencies need to be addressed., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.

Objective: The suitable electrode array choice is broadly discussed in cochlear implantation surgery. Whether to use a shorter electrode length under the aim of structure preservation versus choosing a longer array to achieve a greater cochlear coverage is a matter of debate. The aim of this review is to identify the impact of the insertion depth of a cochlear implant (CI) electrode array on CI users' speech perception outcomes., Databases Reviewed: PubMed was searched for English-language articles that were published in a peer-reviewed journal from 1997 to 2022., Methods: A systematic electronic search of the literature was carried out using PubMed to find relevant literature on the impact of insertion depth on speech perception. The review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines of reporting. Studies in both, children and adults with pre- or postlingual hearing loss, implanted with a CI were included in this study. Articles written in languages other than English, literature reviews, meta-analyses, animal studies, histopathological studies, or studies pertaining exclusively to imaging modalities without reporting correlations between insertion depth and speech outcomes were excluded. The risk of bias was determined using the "Risk of Bias in Nonrandomized Studies of Interventions" tool. Articles were extracted by 2 authors independently using predefined search terms. The titles and abstracts were screened manually to identify studies that potentially meet the inclusion criteria. The extracted information included: the study population, type of hearing loss, outcomes reported, devices used, speech perception outcomes, insertion depth (linear insertion depth and/or the angular insertion depth), and correlation between insertion depth and the speech perception outcomes., Results: A total of 215 relevant studies were assessed for eligibility. Twenty-three studies met the inclusion criteria and were analyzed further. Seven studies found no significant correlation between insertion depth and speech perception outcomes. Fifteen found either a significant positive correlation or a positive effect between insertion depth and speech perception. Only 1 study found a significant negative correlation between insertion depth and speech perception outcomes., Conclusion: Although most studies reported a positive effect of insertion depth on speech perception outcomes, one-third of the identified studies reported no correlation. Thus, the insertion depth must be considered as a contributing factor to speech perception rather than as a major decisive criterion., Registration: This review has been registered in PROSPERO, the international prospective register of systematic reviews (CRD42021257547), available at https://www.crd.york.ac.uk/PROSPERO/., Competing Interests: None declared., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: The cochlear aqueduct (CA), which connects the scala tympani and the subarachnoid space, and its accompanying structures appear to have a significant relevance during cochlear implantation and an accurate visualization in clinical imaging is of great interest. Aims and Objective: This study aims to determine which potential and limitations clinically available imaging modalities have in the visualization of the CA. Methods: Micro-CT, flat-panel volume computed tomography with and without secondary reconstruction (fpVCT, fpVCTseco) and multislice computed tomography (MSCT) of 10 temporal bone specimen were used for 3D analysis of the CA. Results: FpVCTseco proved superior in visualizing the associated structures and lateral portions of the CA, which merge into the basal turn of the cochlea. All clinical imaging modalities proved equal in analyzing the length, total volume of the CA and its area of the medial orifice. Conclusion: The choice of the most accurate clinical imaging modality to evaluate the CA and its associated structures depends on the clinical or scientific question. Furthermore, this study should provide a basis for further investigations analyzing the CA.

Background: Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether the in vivo PET signal can differentiate between varying HNPGL subtypes., Patients and Methods: Fourteen patients with HNPGL received pretherapeutic SSTR-PET/CTs using 68 Ga-DOTATOC. Six (42.9%) patients had a jugular paraganglioma (PGL-J), 5 (35.7%) were diagnosed with carotid paraganglioma (PGL-Cs), and the remaining 3 patients (21.4%) had PGL-C with pathogenic SDHx germline variants (PGL-C-SDH). A visual and quantitative assessment of the primary tumor on SSTR-PET was performed, including SUV max and target-to-background ratio (TBR). Quantitative values were then compared between subgroups of patients affected with different HNPGL entities., Results: On visual assessment, all primary HNPGLs could be identified on SSTR-PET/CT. Quantification of HNPGL revealed substantially elevated SUV max in PGL-J (101.7 ± 58.5) when compared with PGL-C-SDH (13.4 ± 5.6, P < 0.05), but not when compared with PGL-C (66.7 ± 27.3, P = 0.4; PGL-C vs PGL-C-SDH, P = 0.2). TBR of PGL-J (202.9 ± 82.2), however, further differentiated between PGL-C (95.7 ± 45.4, P < 0.05) and PGL-C-SDH (20.4 ± 12.2, P < 0.01; PGL-C vs PGL-C-SDH, P = 0.3). Moreover, whole-body readout revealed metastases in 2/3 (66.7%) of PGL-C-SDH patients, with a single SSTR-expressing skeletal lesion in one subject and bipulmonary lesions in the other patient., Conclusions: In patients with HNPGL, SSTR-PET/CT identified the primary and metastatic disease and provides substantially elevated TBR, indicating excellent image contrast. PET-based quantification can also differentiate between varying HNPGL subtypes., Competing Interests: Conflicts of interest and sources of funding: speaker honoraria from Novartis/AAA (R.A.W.), advisory board work for Novartis/AAA (R.A.W.). No conflict of interest was reported by any of the other authors. This study was partially funded by the German Research Foundation (453989101, T.H., R.A.W.; 507803309, R.A.W.)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: In auditory brainstem implant (ABI) surgery, array placement may be optimized by electrophysiological information of adequate brainstem activation gained from electrically evoked auditory brainstem responses (EABR). This study aims 1) to characterize in detail the EABR from ABI implantation, 2) to introduce an EABR Classification Scheme, and 3) to analyze data for their correlation with individual patients' findings., Methods: Out of a continuous series of 54 patients who received an ABI between 2005 and 2019, 23 Neurofibromatosis Type 2 patients with complete documentation of 154 recordings were selected for offline analysis and for development and evaluation of a new EABR Classification Scheme comprising Class A: three vertex positive peaks, Class B:two peaks, Class C: a combination of one peak and a second melted double peak, Class D: one sole vertex positive peak and Class E: no peaks., Results: All 23 subjects showed EABR at final ABI position and experienced auditory sensations at first activation. The most frequent morphology consisted of two peaks, Classes B and C. Identified mean latencies were for P1 0.42 ms (±0.095), P2 1.42 ms (±0.244) and P3 2.41 ms (±0.329). Peak latencies correlated positively with tumor extensions (p < 0.005)., Conclusions: This study provides clear instructions on optimal EABR performance and evaluation., Significance: The new EABR Classification Scheme relies on a fast "online" identification of vertex positive peaks at the estimated post-artifact phase. The variability in EABR morphology provides an individual snapshot of the actual structural and functional status of the brainstem., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air-liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.

Background: The aim of this study was to determine the read-out capabilities of the novel C-X-C motif chemokine receptor 4 (CXCR4)-targeting radiotracer [ 68 Ga]Ga-PentixaFor compared to the reference radiotracer [ 18 F]FDG in untreated individuals with head and neck squamous cell carcinoma (HNSCC)., Material and Methods: 12 patients with histologically confirmed HNSCC were scheduled for [ 18 F]FDG and [ 68 Ga]Ga-PentixaFor PET/CT. Maximum standardized uptake values (SUV max ) and target-to-background ratios (TBR) were applied with vena cava superior serving as reference. In addition, we compared [ 68 Ga]Ga-PentixaFor-PET findings with immunohistochemical (IHC) results of CXCR4 expression., Results: On visual assessment, [ 18 F]FDG identified more sites of disease, with increased detection rates for both the primary tumor ([ 18 F]FDG, 12/12 [100%] vs. [ 68 Ga]Ga-PentixaFor, 10/12 [83%]) and LN metastases ([ 18 F]FDG, 9/12 [75%] vs. [ 68 Ga]Ga-PentixaFor, 8/12 [67%]). Indicative for improved image contrast using [ 18 F]FDG, quantification showed a higher TBR for the latter radiotracer, when compared to [ 68 Ga]Ga-PentixaFor for all lesions ([ 18 F]FDG, 11.7 ± 8.5 vs. [ 68 Ga]Ga-PentixaFor, 4.3 ± 1.3; P=0.03), primary tumors ([ 18 F]FDG, 13.6 ± 8.7 vs. [ 68 Ga]Ga-PentixaFor, 4.4 ± 1.4; P<0.01), and LN lesions ([ 18 F]FDG, 9.3 ± 10.6 vs. [ 68 Ga]Ga-PentixaFor, 4.7 ± 1.5; P=0.3). IHC showed variable CXCR4 expression in the primary and LN, along with no associations between ex-vivo CXCR4 upregulation and [ 68 Ga]Ga-PentixaFor-based TBR (R=0.33, P=0.39) or SUV max (R=0.44, P=0.2). Of note, IHC also revealed heterogeneous expression of CXCR4 in immune cells in the tumor microenvironment and in germinal centers, indicative for inflammatory reactions., Conclusions: In HNSCC, [ 18 F]FDG demonstrated superior diagnostic performance relative to [ 68 Ga]Ga-PentixaFor, in particular for assessment of the primary. Based on the IHC analyses, these findings may be explained by CXCR4 upregulation not only by tumor but also by immune cells in the tumor microenvironment., Competing Interests: R.A.W. has received speaker honoraria from PentixaPharm and is involved in [68Ga]Ga-Pentixafor PET Imaging in PAN Cancer (FORPAN), sponsored and planned by PentixaPharm., (AJNMMI Copyright © 2023.)

Neural stem cells (NSCs) have previously been described up to the adult stage in the rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. A better understanding of molecular factors affecting NSCs and neurogenesis is of interest as they represent potential targets to treat the cause of neurologically based hearing disorders. The role of genes affecting NSC development and neurogenesis in CN over time on hearing capacity has remained unclear. This study investigated the mRNA abundance of genes influencing NSCs and neurogenesis in rats' CN over time. The CN of rats on postnatal days 6, 12, and 24 were examined. Real-time quantitative polymerase chain reaction arrays were used to compare mRNA levels of 84 genes relevant to NSCs and neurogenesis. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected in the rat CN. Additionally, crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. The results of this work should contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway.

Purpose: Local failure and distant metastases occur frequently in sinonasal mucosal melanoma (SNMM). Response rates to chemotherapy are low and targetable mutations are rarely detected. However, there is increasing data indicating efficacy of immune checkpoint inhibition (ICI). The aim of this retrospective monocenter study was to assess the mutational landscape and to evaluate the outcome of surgical treatment and ICI in SNMM in a real-world setting., Methods: Thirty-eight SNMM patients being treated between 1999 and 2020 at our institution were retrospectively reviewed. Survival curves were generated according to Kaplan-Meier and compared by the log-rank test., Results: Local failure was seen in 60% of patients treated in a curative intent. Overall, 24% of all patients suffered from regional and 66% from distant metastases. Next generation sequencing revealed mutations of BRAF, NRAS and KRAS. One out of three patients treated with a primary ICI showed a complete response (CR) and two showed progressive disease. Eleven patients received ICI as a palliative treatment. CR could be observed in three patients and stable disease in one patient. In the whole study population, the 5-year overall survival rate (OS) was 26%. OS was better for patients who received ICI during the course of disease., Conclusions: Recurrences and distant metastases are frequent in SNMM. Durable CR could be observed after primary and palliative ICI. Therefore, ICI in a palliative, adjuvant or even neoadjuvant setting might play a promising role in SNMM therapy while targetable mutations are rarely detected., (© 2023. The Author(s).)

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, which were determined via post-operative high-resolution flat panel volume computer tomography and clinical fitting software. The outcome measures were speech understanding in quiet and noise and self-perceived sound quality with the CBF map and with the ABF map. Participants were 10 experienced bilateral CI users. The ABF map provided better speech understanding in quiet and noisy environments compared to the CBF map. Additionally, two approaches of reducing the frequency-to-place mismatch revealed that participants are more likely to accept the ABF map if their electrode array is inserted deep enough to stimulate the apical region of their cochlea. This suggests an Angular Insertion Depth of the most apical contact of around 720°-620°. Participants had better speech understanding in quiet and noise with the ABF map. The maps' self-perceived sound quality was similar. ABF mapping may be an effective tool for compensating the frequency-to-place mismatch in experienced bilateral CI users.

Objective: To investigate the benefit of intraoperative auditory brainstem response (ABR) measurements in revision active middle ear implant surgery., Study Design: Retrospective data analysis., Setting: Tertiary referral center with a large active middle ear implant program., Main Outcome Measures: Intraoperative ABR thresholds, audiogram, sound field thresholds, speech understanding in the Freiburger monosyllabic word test., Patients: Fourteen patients with active middle ear implant revision surgery., Results: The application of the ABR measurement resulted in improved sound field thresholds and enhanced speech understanding. Analysis revealed a significant correlation of intraoperative gain in ABR threshold with the postoperative gain in sound field thresholds., Conclusion: ABR monitoring can be a useful tool to provide information intraoperatively about the coupling efficiency of the FMT. Especially in revision surgeries, this might help to improve postoperative hearing success., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.

Objectives: In cochlear implantation, preoperative prediction of electrode position has recently gained increasing attention. Currently, planning is usually done by multislice CT (MSCT). However, flat-panel volume CT (fpVCT) and its secondary reconstructions (fpVCT SECO ) allow for more precise visualization of the cochlea. Combined with a newly developed otological planning software, the position of every single contact can be effectively predicted. In this study it was investigated how accurately radiological prediction forecasts the postoperative electrode localization and whether higher image resolution is advantageous., Methods: Utilizing otological planning software (OTOPLAN®) and different clinical imaging modalities (MSCT, fpVCT and fpVCT SECO ) the electrode localization [angular insertion depth (AID)] and respective contact frequencies were predicted preoperatively and examined postoperatively. Furthermore, inter-electrode-distance (IED) and inter-electrode-frequency difference (IEFD) were evaluated postoperatively., Results: Measurements revealed a preoperative overestimation of AID. Corresponding frequencies were also miscalculated. Determination of IED and IEFD revealed discrepancies at the transition from the basal to the middle turn and round window to the basal turn. All predictions and discrepancies were lowest when using fpVCT SECO ., Conclusion: The postoperative electrode position can be predicted quite accurately using otological planning software. However, because of several potential misjudgments, high-resolution imaging, such as offered by fpVCT SECO , should be used pre- and postoperatively.

Printer toner particles (TPs) are a common, potentially hazardous substance, with an unclear toxicological impact on the respiratory mucosa. Most of the airways surface is covered by a ciliated respiratory mucosa, therefore appropriate tissue models of the respiratory epithelium with a high in vivo correlation are necessary for in vitro evaluation of airborne pollutants toxicology and the impact on the functional integrity. The aim of this study is the evaluation of TPs toxicology in a human primary cell-based air-liquid-interface (ALI) model of respiratory mucosa. The TPs were analyzed and characterized by scanning electron microscopy, pyrolysis and X-ray fluorescence spectrometry. ALI models of 10 patients were created using the epithelial cells and fibroblasts derived from nasal mucosa samples. TPs were applied to the ALI models via a modified Vitrocell® cloud and submerged in the dosing 0.89 - 892.96 µg/ cm 2 . Particle exposure and intracellular distribution were evaluated by electron microscopy. The MTT assay and the comet assay were used to investigate cytotoxicity and genotoxicity, respectively. The used TPs showed an average particle size of 3 - 8 µm. Mainly carbon, hydrogen, silicon, nitrogen, tin, benzene and benzene derivates were detected as chemical ingredients. By histomorphology and electron microscopy we observed the development of a highly functional, pseudostratified epithelium with a continuous layer of cilia. Using electron microscopy, TPs could be detected on the cilia surface and also intracellularly. Cytotoxicity was detected from 9 µg/ cm 2 and higher, but no genotoxicity after ALI and submerged exposure. The ALI with primary nasal cells represents a highly functional model of the respiratory epithelium in terms of histomorphology and mucociliary differentiation. The toxicological results indicate a weak TP-concentration-dependent cytotoxicity. AVAILABILITY OF DATA AND MATERIALS: The datasets used and analysed during the current study are available from the corresponding author on reasonable request., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Till Jasper Meyer reports financial support was provided by Interdisciplinary Centre for Clinical Science (IZKF) at the University of Würzburg. Maria R. Steinke reports financial support was provided by Deutsche Forschungsgemeinschaft. Stephan Hackenberg reports financial support was provided by Deutsche Forschungsgemeinschaft., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The organ of Corti, located in the cochlea within the inner ear is the receptor organ for hearing. It converts auditory signals into neuronal action potentials that are transmitted to the brain for further processing. The mature organ of Corti consists of a variety of highly differentiated sensory cells that fulfil unique tasks in the processing of auditory signals. The actin and microtubule cytoskeleton play essential function in hearing, however so far, more attention has been paid to the role of actin. Microtubules play important roles in maintaining cellular structure and intracellular transport in virtually all eukaryotic cells. Their functions are controlled by interactions with a large variety of microtubule-associated proteins (MAPs) and molecular motors. Current advances show that tubulin posttranslational modifications, as well as tubulin isotypes could play key roles in modulating microtubule properties and functions in cells. These mechanisms could have various effects on the stability and functions of microtubules in the highly specialised cells of the cochlea. Here, we review the current understanding of the role of microtubule-regulating mechanisms in the function of the cochlea and their implications for hearing, which highlights the importance of microtubules in the field of hearing research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The benefit of hearing rehabilitation is often measured using audiological tests or subjective questionnaires/interviews. It is important to consider both aspects in order to evaluate the overall benefits. Currently, there is no standardized method for reporting combined audiological and patient reported subjective outcome measures in clinical practice. Therefore, this study focuses on showing the patient's audiological, as well as subjective outcomes in one graph using data from an existing study., Method: The present paper illustrated a graph presenting data on four quadrants with audiological and subjective findings. These quadrants represented speech comprehension in quiet (unaided vs. aided) as WRS% at 65 dB SPL, speech recognition in noise (unaided vs. aided) as SRT dB SNR, sound field threshold (unaided vs. aided) as PTA 4 in dB HL, wearing time and patient satisfaction questionnaire results., Results: As an example, the HEARRING graph in this paper represented audiological and subjective datasets on a single patient level or a cohort of patients for an active bone conduction hearing implant solution. The graph offered the option to follow the user's performance in time., Conclusion: The HEARRING graph allowed representation of a combination of audiological measures with patient reported outcomes in one single graph, indicating the overall benefit of the intervention. In addition, the correlation and consistency between some results (e.g., aided threshold and aided WRS) can be better visualized. Those users who lacked performance benefits on one or more parameters and called for further insight could be visually identified.

Objectives: Intelligence as a construct of cognitive abilities is the basis of knowledge and skill acquisition and the main predictor of academic achievement. As a broad construct, it is usually divided into subdomains, such as nonverbal and verbal intelligence. Verbal intelligence is one domain of intelligence but is not synonymous with specific linguistic abilities like grammar proficiency. We aim to address the general expectation that early cochlear implantation enables children who are hard of hearing to develop comprehensively, including with respect to verbal intelligence. The primary purpose of this study is to trace the longitudinal development of verbal and nonverbal intelligence in children with cochlear implants (CIs)., Design: Sixteen children with congenital hearing loss who received unilateral or bilateral implants and completed at least two intelligence assessments around the age of school entrance were included in the study. The first assessment was performed around 3 years after CI fitting (chronological age range: 3.93 to 7.03 years). The second assessment was performed approximately 2 years after the first assessment. To analyze verbal and nonverbal IQ in conjunction and across children at different ages, we used corresponding standardized and normalized tests from the same test family (Wechsler Preschool and Primary Scale of Intelligence and/or Wechsler Intelligence Scale for Children)., Results: Regarding longitudinal development, both verbal and nonverbal IQ increased, but verbal IQ increased more substantially over time. At the time of the second measurement, verbal and nonverbal IQ were on a comparable level. Nevertheless, we also observed strong inter-individual differences. The duration between both assessments was significantly associated with verbal IQ at the second measurement time point and thus with verbal IQ gain over time. Education mode (regular vs. special kindergarten/school) was significantly correlated with nonverbal IQ at the second assessment time point., Conclusions: The results, despite the small sample size, clearly suggest that children with CIs can achieve intellectual abilities comparable to those of their normal-hearing peers by around the third year after initial CI fitting, and they continue to improve over the following 2 years. We recommend further research focusing on verbal IQ assessed around the age of school entrance to be used as a predictor for further development and for the establishment of an individual educational program., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The start of the COVID-19 pandemic led to enormous challenges for global healthcare, as capacities and resources had to be made available quickly for the treatment of COVID-19 patients. As a result, restrictions had to be accepted, especially in the care of oncological patients. The collateral damage of these limitations inevitably also affects patients with head and neck cancer. This review article summarizes the development of tumor incidences during the pandemic, internationally developed guidelines for the care of patients with head and neck cancer and studies on the delay in oncological therapies and mortality. In addition, the effects on the mental health of the patients, the psychosocial consequences and ethical issues are examined. In perspective, preventive measures for such negative collateral effects in future pandemics are discussed using the example of a concept for application software (app)-based digital care for patients with head and neck cancer., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.

Cancer-associated fibroblasts (CAF) in the tumor microenvironment have a decisive influence on tumor growth and metastatic behavior. The cellular origins as well as the stimuli leading to CAF formation are heterogenous, impeding a precise characterization. Aim of this study was to analyze the influence of cytokines secreted in the process of wound healing, tumor cell-associated paracrine-secreted factors, and direct cell-cell contact on the expression of the CAF-associated markers fibroblast activation protein (FAP), α-smooth muscle actin (α-SMA), thrombospondin-1 (THBS1), and tenascin-c (TNC) by RT-PCR in mesenchymal stem cells (MSC). Cells developed different morphological characteristics after incubation with wound fluid (WF). Moreover, expression of FAP and α-SMA in MSC was significantly reduced after WF compared to tumor-conditioned medium and in co-culture with tumor cells; THBS1 and TNC were not significantly altered after any of the different incubation methods. There were no alterations of expression patterns of FAP and α-SMA in the immunohistochemical analysis. Differ-ences in the cytokine composition of the media were found in the dot blot. The heterogeneity of the results emphasizes the complexity of the interactions of tumor cells and cells of the microenvironment, particularly through the addition of human-derived WF., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1-18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved., Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient's outcome., What Is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery., What Is New: • The focus identification has no impact on patient's outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved., (© 2022. The Author(s).)

Introduction: Aspergillus fumigatus belongs to the saprophytic fungi, and its spores form a significant part of the daily load of fungal spores inhaled as particles in aerosols. A. fumigatus is a possible T-cell activator. Its contribution to the pathogenesis of chronic rhinosinusitis (CRS) is controversially discussed. The aim of this study was to detect and characterize A. fumigatus-specific CD4+ and CD8+ T cells in patients with CRS with (CRSwNP) and without (CRSsNP) nasal polyps., Methods: Tissue and blood samples were collected from patients who underwent paranasal sinus surgery due to CRSwNP or CRSsNP. Afterward, purified CD4+ and CD8+ cells were cultured together with antigen-presenting cells. A peptide mix derived from A. fumigatus antigen was added to the cultures. After 6 days, multicolor flow cytometry was performed, and proliferation was measured using the marker Ki-67. Cytokine secretion was quantified from the supernatant of the cell culture., Results: Significant differences in the proliferation of nasal CD4+ T cells to A. fumigatus antigen were observed for cells from patients with CRSwNP in comparison to CRSsNP, while no differences were found between nasal and peripheral blood T cells. The activation of tissue-derived CD4+ T cells was associated with significantly higher concentrations of IL-4, IL-5, and IL-17a in the cell culture from patients with CRSwNP in comparison to CRSsNP and/or healthy controls., Conclusion: Our findings indicate that patients with CRSwNP harbor a higher proportion of A. fumigatus-reactive CD4+ T cells in the nasal mucosa than patients with CRSsNP. A. fumigatus-reactive CD4+ T cells of CRSwNP patients secreted TH2 cytokines and IL-17. Our findings suggest a role for A. fumigatus in the pathogenesis of CRSwNP and provide a rationale for targeted therapies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

A platform to help clinicians ensure that hearing device candidates are informed about the benefits and drawbacks of their recommended treatment option would be of clinical counselling benefit because it could help each candidate form realistic expectations about life with their treatment option. Following the World Café approach, 54 participants (surgeons, audiologist, and researchers) generated lists of the benefits and drawbacks of each treatment option for single-sided deafness (SSD) and bone conduction (BC) solutions. They then prioritized the benefits and drawbacks. After the World Café, literature research was performed on each topic to check if the statements (on benefits and drawbacks) are supported by quality peer-reviewed publications. Each participant was surveyed to ensure a collective agreement was reached. The HEARRING Counselling 1.0 Platform was developed. Thus far, sections for SSD and BC solutions have been completed. Initial feedback has been highly positive. The platform will be expanded to cover middle ear implant solutions and cochlear implants. A plan is in place to ensure the information continues to be timely. The HEARRING Counselling 1.0 helps clinicians provide comprehensive information to candidates about their treatment option and thereby helps establish that candidates have realistic expectations about the benefits and drawbacks of device use.

Purpose: Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO 2 laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO 2 laser., Methods: Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups., Results: The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection., Conclusion: The flexible CO 2 laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view., (© 2022. The Author(s).)

Objective: To evaluate a new methodological approach of applying anatomy-based fitting (ABF) in experienced cochlear implant (CI) users., Participants: Three experienced unilateral and bilateral CI users with postlingual hearing loss., Intervention: Postoperative imaging, via a high-volume Dyna computed tomography, and exact electrode measurement positions were integrated into the clinical fitting software following a new procedure, which adapted individual frequency bandwidths within the audio processor., Main Outcome Measures: Speech perception in quiet and noise, clinical mapping, and self-perceived level of auditory benefit were assessed., Results: For each CI user, ABF mapping provided better speech perception in quiet and in noise compared with the original clinical fitting mapping. In addition, ABF mapping was accepted in CI users despite unequal bilateral array insertion depths and lengths; however, acceptance was only established if the point of first electrode contact was less than 230 Hz., Conclusions: ABF mapping increased the acceptance in CI users with longer electrode arrays and in bilateral CI users who were unsatisfied with their device experience. A larger prospective, randomized investigation is currently underway to assess longitudinal outcomes with ABF mapping., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

The inpatient care of children after ENT surgery is organized heterogeneously across Germany. In this statement, the working group on Pediatric ENT comments a national survey on the status quo of child care after ENT interventions in German hospitals. The statement should serve as a basis for further interdisciplinary discussion., (© 2022. The Author(s).)

Human mesenchymal stem cells (hMSC) are multipotent cells with the ability to differentiate into a range of different cell types, including fat, bone, cartilage or muscle. A pro-tumorigenic effect of hMSC has been previously reported as part of the tumor stroma. In addition, studies have previously revealed the influence of hematopoietic and lymphoid tumors on hMSC differentiation to support their own growth. However, this possible phenomenon has not been explored in solid malignancies. Therefore, the aim of the present study was to investigate the effects of head and neck squamous cell carcinoma (HNSCC) lines Cal27 and HLaC78 on the induction of osteogenic and adipogenic differentiation in hMSCs. Native hMSCs were co-cultured with Cal27 and HLaC78 cells for 3 weeks. Subsequently, hMSC differentiation was assessed using reverse transcription-PCR and using Oil Red O and von Kossa staining. Furthermore, the effects of differentiated hMSCs on Cal27 and HLaC78 were examined. For this purpose, hMSCs differentiated into the adipogenic (adipo-hMSC) and osteogenic (osteo-hMSC) lineages were co-cultured with Cal27 and HLaC78. Cell viability, cytokine secretion and activation of STAT3 signaling were measured by cell counting, dot blot assay (42 cytokines with focus on IL-6) and western blotting (STAT3, phosphorylated STAT3, β-actin), respectively. Co-culturing hMSCs with Cal27 and HLaC78 cells resulted in both adipogenic and osteogenic differentiation. In addition, the viability of Cal27 and HLaC78 cells was found to be increased after co-cultivation with adipo-hMSCs, compared with that of cells co-cultured with osteo-hMSC. According to western blotting results, Cal27 cells incubated with adipo-hMSCs exhibited increased STAT3 activation, compared with that in cells co-cultured with native hMSCs and osteo-hMSCs. IL-6 concentration in the media of Cal27 and HLaC78 after co-cultivation with respectively incubation with conditioned media of hMSCs, adipo-hMSCs and osteo-hMSCs were also found to be increased compared with that in the media of Cal27 and HLaC78 cells incubated with DMEM. To conclude, HNSCC cell lines Cal27 and HLaC78 induced hMSC differentiation towards the adipogenic and osteogenic lineages in vitro . Furthermore, a proliferative effect of adipo-hMSCs on Cal27 and HLaC78 cells was revealed with STAT3 activation as a possible mechanism. These results warrant further investigation of the interaction between HNSCC cells and hMSCs, with focus on the mechanism underlying the differentiation of hMSCs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Meyer et al.)

This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.

Objectives: The SONNET 2 audio processor features ambient noise reduction (ANR), transient-noise reduction (TNR), and adaptive intelligence (AI). The primary aim of this study was to evaluate if using these features improves speech perception in noise, subjective listening effort, and sound quality., Design: In this prospective longitudinal study, twenty adult SONNET users were fitted with the SONNET 2 audio processor, configured either as a default SONNET (no ANR/TNR/AI), with mild ANR/TNR, with strong ANR/TNR, with mild AI, and with strong AI. Speech perception in noise was assessed in speech and stationary noise from the front (S0N0); speech, stationary noise, and transient noise from the front (S0N0T0); and speech from the front in spatially-distributed stationary noise (S0N±45N±135). Listening effort, subjective sound quality, and device/setup preference were assessed., Results: In the S0N0 setup, speech perception in noise was significantly better with the SONNET 2 when using ANR/TNR in the mild setup than with the SONNET or the SONNET 2 in the default SONNET configuration. In the S0N±45N±135 setup, speech understanding was significantly better in all four SONNET 2 configurations than with the SONNET or the SONNET 2 in the default SONNET configuration (a 1.26-2.55 dB SRT80 benefit). Subjects tolerated consistently lower signal-to-noise values with the SONNET 2 configurations using ANR/TNR than with the default SONNET configuration in all listening effort categories. All SONNET 2 configurations using ANR/TNR were preferred and better rated in speech in stationary and/or transient noise compared to the default SONNET configuration. Sound quality and pleasantness were better in those SONNET 2 configurations. Subjects strongly preferred the SONNET 2 configurations over the SONNET configuration., Conclusions: The new front-end features implemented in the SONNET 2 audio processor objectively improve speech perception in noise. Subjects preferred the SONNET 2, over the SONNET, in the presence of stationary and transient noise., Competing Interests: The authors have declared that no competing interests exist.

This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT SECO ). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion., (© 2022. The Author(s).)

Cochlear implants (CI) are an established treatment for people with deafness or severe hearing loss. To restore patients' hearing an electrode array (EA) of the CI is inserted into the cochlea to stimulate the auditory nerve. Thereby, the exact positioning and gentle insertion of the EA is crucial for optimal hearing perception outcome. Currently, only microscopic vision is available for entering the cochlea, but the critical intracochlear process during EA insertion is like a "black box" and the surgeon has to rely on haptic feedback. Methods for visualizing the insertion process during surgery are inaccurate or not suitable for routine use due to radiation exposure. To address this problem, we developed a computer-assisted and image-guided cochlear implantation system with an exact real-time visualization of the EA position during the insertion process. The system is based on an electromagnetic tracking system that measures the position and orientation of a sensor integrated into the tip of a EA prototype and visualizes it in presurgical image data. A first experiment with our system showed that a EA prototype could be inserted into a cochlea of a human temporal bone and placed with an accuracy of [Formula: see text]. A maximum insertion angle of 120° was achieved.

The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bieniussa, Kahraman, Skornicka, Schulte, Voelker, Jablonka, Hagen and Rak.)