[The multicenter registry "oropharyngeal cancer" of the German ENT Study Center - First Results]. / Das multizentrische Register "Oropharynxkarzinom" des Deutschen Studienzentrums für HNO ­ erste Ergebnisse.

BACKGROUND: The number of oropharyngeal squamous cell carcinomas (OPSCC) caused by human papillomavirus (HPV) has increased significantly in recent years. However, no robust data exist on the incidence of HPV-associated OPSCC as well as their treatment in central Europe. AIM OF THE WORK: The aim is to establish an epidemiological register of patients with OPSCC in central Europe. MATERIAL AND METHODS: To close the evidence gap on p16-positive OPSCC, a prospective multicenter registry on incidence, risk factors and treatment of OPSCC in certified Head and Neck Tumor Centers according to the German Cancer Society was established. Data collection was pseudonymously performed using the web-based Research Electronic Data Capture (REDCap). RESULTS: In 2022 and 2023, 1312 patients with OPSCC from 34 centers were included. 720 patients (58.2 %) were p16-positive. The most common locations of p16-positive primary tumors were the tonsil (49.9 %) and the base of the tongue (28.7 %). 63.1 % of p16-positive OPSCC received primary surgical treatment, whereas only 48.0 % of p16-negative tumors received primary surgery. Differences are also evident in the adjuvant therapy: 58 % of p16-negative OPSCC did not receive adjuvant therapy after surgery, compared with 37.1 % of p16-positive OPSCC. CONCLUSION: The start of the OPSCC registry study was technically smooth. This registry provides an insight into the current care situation of OPSCC in German-speaking countries and will gain importance through the participation of more centers.

Safety and efficacy of the mAXIS stapes prosthesis.

PURPOSE: Otosclerosis leads to a fixed stapes footplate and thus to hearing loss. The predominant treatment method is surgery, with various types of stapes prostheses available. The aim of this study was to investigate the safety and efficacy of the new mAXIS Stapes Prosthesis. METHODS: 34 cases of otosclerosis were implanted with the new mAXIS Stapes Prosthesis. Comprehensive clinical assessments, including pre- and postoperative pure tone audiometry was performed at short-term (ST) follow-up at 25 (± 15) days and mid-term (MT) follow-up at 181 (± 107) days. The pure tone average of 0.5, 1, 2 and 3 kHz (PTA4) was calculated. RESULTS: In all cases, the application of the prosthesis was successful and straightforward. The postoperative PTA4 air-bone gap was 10.7 ± 5.2 dB at ST follow-up (n = 34) and 8.3 ± 4.1 dB at MT follow-up (n = 18). In 61% of cases, the ABG-closure was within 10 dB and in 100% of cases within 20 dB at MT follow-up. CONCLUSION: Findings of this study support that the mAXIS Stapes Prosthesis is safe for implantation and shows promising audiological outcome. Future investigations will contribute its long-term efficacy and safety profile.

Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.

Introduction: Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Methods: Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. Results: The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. Discussion: This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.

Safety and performance of the new med-el total ossicular replacement prostheses.

PURPOSE: This multicentric, retrospective study provides safety and performance data of the MED-EL total ossicular replacement prostheses (TORP). METHODS: Patients underwent tympanoplasty with mXACT Total Prosthesis Center, mXACT Total Prosthesis Offcenter or mXACT PRO Total Prosthesis. The clinical data were retrospectively analyzed. Follow-up examination included access to the medical record (for adverse events) of the patients, ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. RESULTS: 103 patients were implanted with a TORP. 102 (88 adults, 14 children; 37 CHL, 64 MHL, 1 not specified) patients were analyzed for safety and 92 (79 adults, 13 children) patients for performance of the prostheses. ADVERSE EVENTS RESULTS (N = 102): In 1 patient (child, mXACT Total Prosthesis Offcenter) a prosthesis dislocation was reported, which lead to a revision surgery. No prosthesis extrusion or migration was reported. AUDIOLOGICAL RESULTS (N = 92): 49 (53.3%) of the 92 patients had a PTA4 ABG of ≤ 20 dB and therefore a successful rehabilitation. The mean post-operative PTA4 ABG of all 92 patients was 21.0 ± 9.7 dB. The first endpoint, improvement in post-operative PTA4 ABG of ≤ 20 dB by ≥ 25% of the patients was achieved. The individual Δ BC PTA4 (post-operative minus pre-operative BC PTA4) thresholds were stable (within ± 5 dB HL) in 91 (98.9%) patients. 1 patient had a BC PTA4 deterioration of 11.3 dB HL. CONCLUSION: The MED-EL TORPs are safe and effective for middle ear reconstruction. Trial registration number NCT05565339, September 09, 2022, retrospectively registered.

Automated Capillary Electrophoresis Immunoblot for the Detection of Alpha-Synuclein in Mouse Tissue.

Background: Alpha-synuclein (aSyn) is a key player in neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies, or multiple system atrophy. aSyn is expressed throughout the brain, and can also be detected in various peripheral tissues. In fact, initial symptoms of PD are non-motoric and include autonomic dysfunction, suggesting that the periphery might play an important role in early development of the disease. aSyn is expressed at relatively low levels in non-central tissues, which brings challenges for its detection and quantification in different tissues. Objective: Our goal was to assess the sensitivity of aSyn detection in central and peripheral mouse tissues through capillary electrophoresis (CE) immunoblot, considering the traditional SDS-PAGE immunoblot as the current standard. Methods: Tissues from central and non-central origin from wild type mice were extracted, and included midbrain, inner ear, and esophagus/stomach. aSyn detection was assessed through immunoblotting using Simple Western size-based CE and SDS-PAGE. Results: CE immunoblots show a consistent detection of aSyn in central and peripheral tissues. Through SDS-PAGE, immunoblots revealed a reliable signal corresponding to aSyn, particularly following membrane fixation. Conclusion: Our results suggest a reliable detection of aSyn in central and peripheral tissues using the CE Simple Western immunoblot system. These observations can serve as preliminary datasets when aiming to formally compare CE with SDS-PAGE, as well as for further characterization of aSyn using this technique.

[High interaction potential of online-only courses with breakout sessions-results of a pilot study]. / Hohes Interaktionspotenzial volldigitaler Lehrveranstaltungen mit Breakout-Sessions ­ Ergebnisse einer Pilotstudie.

BACKGROUND: The flipped classroom (FC) is nowadays a popular principle of blended student-centered learning. Students first prepare basic knowledge at home and subsequently meet for consolidation and a more in-depth look at a certain topic. During the COVID-19 pandemic, several groups developed approaches to also transform the characteristic FC second session into an online-only format. OBJECTIVE: Herein, we present a pilot study on establishing an online-only FC format with elements of collaborative learning and its evaluation by medical students. MATERIALS AND METHODS: The FC design related to diseases of the salivary glands was transformed into an online-only event. After studying the basic information online, supported by self-made interactive videos and/or lecture recordings, students met in a video conference enriched by breakout sessions, interactive demonstration of the related clinical examination including ultrasound, and a formative assessment. A questionnaire with 27 items was answered by participants to evaluate the concept and the event. RESULTS: Use of common hard- and software systems led to a technically stable video conference. A total of 55 students completed the questionnaire and were included into data analysis. During the breakout sessions, lively interaction between participants was observed. The evaluation of both the event itself and the related learning progress showed good results despite the lack of preparation beforehand in 27% of participants. CONCLUSION: Online-only FC designs can result in high satisfaction. High quality of online preparation, a solid technical platform, accurate time management, and a reasonable selection of topics are the main parameters contributing to successful course design. Nowadays, embedding medical imaging can be realized in appropriate quality for educational purposes. The implementation of breakout sessions and voting tools enables collaborative online learning with high levels of interaction and satisfaction for both teachers and students.

Partial Ossicular Reconstruction With a Novel Ball Joint Prosthesis: The mCLIP ARC Partial Prosthesis.

OBJECTIVE: Middle ear surgery involves reconstruction of the ossicular chain, predominately using rigid implants. New middle ear prostheses strive to mimic the physiologic micromovements of the ossicular chain and prevent dislocation, protrusion, and preloading of the annular ligament due to pressure fluctuations. METHODS: Thirty-five patients were included in a monocentric, prospective observational study. Patients received tympanoplasty with ossicular reconstruction using the mCLIP ARC partial prosthesis. This titanium prosthesis is equipped with a clip mechanism for coupling at the stapes and a ball joint connecting headplate and shaft. At short-term (ST) and mid-term (MT) follow-up, pure-tone audiometry was performed and the pure tone average of 0.5, 1, 2, and 3 kHz (PTA4) was calculated. The audiological outcome was compared with retrospective data of the Dresden titanium clip prosthesis. RESULTS: The new prosthesis shows favorable clinical results. Pure-tone audiometry showed satisfactory results in ST and MT follow-up, with the PTA4 air-bone gap (ABG) decreasing from 24.5 (±11) dB to 17.4 (±7.9) dB at the ST follow-up at 27 days to 15.6 (±10.3) dB at MT follow-up at 196 days (n = 32). A PTA4-ABG value of less than 20 dB was achieved by 63% of patients at ST follow-up and by 77% at MT follow-up. There was no significant difference in PTA4 ABG compared to the Dresden titanium clip prosthesis during ST follow-up (p = 0.18). CONCLUSION: The mCLIP ARC partial prosthesis, a new middle ear prosthesis with a balanced ball joint, shows promising audiological results and is a safe and effective choice for patients with chronic ear disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3323-3328, 2024.

Assessment of oropharyngeal respiratory volume and sleep apnoea scores using peripheral arterial tonometry may improve diagnosis and treatment planning of combined dysgnathia therapy approaches.

BACKGROUND: Increased daytime sleepiness is a frequently reported symptom in patients with pronounced dysgnathia. OBJECTIVES: This study investigated possible correlations using home peripheral arterial tonometry (PAT) and oropharyngeal airway volume determination in patients with dysgnathia and daytime sleepiness. METHODS: Twenty patients (13 male, median age 27.6 ± 6.8 years) with abnormal sleep history and 10 skeletal neutral configured controls (6 male, median age 29.5 ± 4.2 years) with normal sleep history were examined. Patients and controls were evaluated for apnoea-hypopnoea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index (ODI), snoring volume (dB), total sleep time (TST) and REM-percentage (REM). Airway volumetry was measured via CBCT. Individual user experience for PAT was assessed using the User Experience Questionnaire (UEQ). RESULTS: Patients had significantly higher respiratory scores than controls. AHI increased 4.6-fold (p = .006), RDI 2.5-fold (p = .008) and ODI 6.4-fold (p < .001). Oropharyngeal volumes showed a 30% decrease (p = .003). dB, TST and REM showed no significant differences. AHI (r = -.51; p = .005), ODI (r = -.60; p < .001) and RDI (r = -.45; p = .016) correlated negatively with pharyngeal volume. Wits appraisal correlated negatively with oropharyngeal volume (r = -.47; p = .010) and positively with AHI (r = .41; p = .03) and ODI (r = .49; p = .007). dB and TST (r = -.49; p = .008) and REM and RDI (r = -.43; p = .02) correlated negatively. UEQ-KPI (2.17 ± 0.24) confirmed excellent usability of PAT. CONCLUSION: Patients with mandibular retrognathia and abnormal sleep history showed significantly higher respiratory indices and smaller oropharyngeal volumes than neutrally configured controls. The dygnathia severity directly influenced the risk of obstructive sleep apnoea.

Short-term safety and effectiveness of the mCLIP partial prosthesis.

PURPOSE: This multicentric, retrospective study aimed to analyze the short-term safety and effectiveness of the mCLIP Partial Prosthesis. METHODS: Patients underwent tympanoplasty with implantation of a mCLIP Partial Prosthesis. Follow-up examination included ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. Thus, the follow-up times of each study center were different, which resulted in different follow-up times for the audiological analysis and for adverse events (AE). RESULTS: 72 (66 adults, 6 children) patients were implanted with the mCLIP Partial Prosthesis. 68 (62 adults, 6 children) patients underwent audiological examination; all 72 patients were examined for adverse events. All patients (N = 68): 72.1% of the patients showed a PTA4 ABG of ≤ 20 dB. Individual post-operative bone conduction (BC) PTA4 thresholds were stable in 67 patients. The mean post-operative follow-up time was 78 ± 46 days. Children (N = 6): 5 out of 6 children showed a PTA4 ABG of ≤ 20 dB. None of the children reported a BC PTA4 deterioration of > 10 dB HL after the implantation. The mean post-operative follow-up time was 101 ± 45 days. Adverse events (all patients, N = 72): 15 (14 adults, 1 child) patients had AEs (27 AEs and 2 Follow-Ups). The mean post-operative follow-up time was 375 days. CONCLUSION: Clinical data show satisfactory audiological parameters after implantation of the mCLIP Partial Prosthesis. The prosthesis is safe and effective for implantation in children and adults. TRIAL REGISTRATION NUMBER: NCT05565339, 09 September 2022, retrospectively registered.

Oral health in patients with different sites of head and neck squamous cell carcinoma is not different.

Oral health might not only act as risk factor for head and neck squamous cell carcinoma (HNSCC), but might also have a predictive value for the patients' survival. Currently, information on the effect of oral health on survival of patients with different sites of HNSCC is lacking. This single-center retrospective study aimed to compare oral health in patients with different sites of HNSCC and to analyse whether oral health is associated with survival in the different subsets of HNSCC patients. Dental records of HNSCC patients referred for dental assessment prior to radio(chemo)therapy were included. Patient-related parameters (age at time of diagnosis, sex, tobacco exposure, alcohol consumption, HPV status), treatment data (primary treatment, intent), performance status, tumor demographics (anatomical site, TNM staging), and oral health parameters (DMFT, periodontal health, teeth with/without root canal treatment and with/without periodontitis apicalis) were obtained. Oral health parameters were compared between different anatomical sites. Survival of all HNSCC patients and of individual subsets was assessed using Kaplan-Meier statistics, and the effect of tumor demographics, patient-related parameters, and oral health on survival was analysed by cox regression analyses (α = 5%). 371 patients with HNSCC (oral: n = 86, oropharyngeal: n = 174, hypopharyngeal: n = 59, laryngeal: n = 15, other: n = 37) were included. Oral health parameters did not differ between subsets (padj.≥0.199). Five-year cumulative survival of HNSCC patients amounted to 78.6%. Only for HNSCC originating in the oral cavity and oropharynx, survival was associated with the treatment intent (p = 0.015) or performance status (p = 0.007) in the multivariable analyses, respectively. Within the limitations of this study, oral health was not different between different subsets and had no significant effect on survival of HNSCC patients.

Inconsistent Skin Prick Tests for Allergy to Birch Homologous Trees May Result from Cross-Reacting Allergens or Technical Errors.

INTRODUCTION: Skin prick tests (SPTs) are the gold standard for diagnosis of allergic rhinitis (AR). A decrease in the number of allergens included in standard SPT panels has recently been debated - particularly regarding the cross-reacting homologous pollen from birch, alder, and hazel trees - but has not yet been implemented in clinical guidelines. METHODS: A subgroup of patients with AR (n = 69) who showed inconsistent SPT results among birch, alder, and hazel was investigated in detail. Beyond SPT, patient workup included assessment of clinical relevance and various serological parameters (total IgE, and specific IgE to birch, alder, and hazel and to Bet v 1, Bet v 2, and Bet v 4). RESULTS: More than half the study group had negative SPT results for birch but positive results for alder and/or hazel, and 87% of the study group was polysensitized, showing at least one more positive SPT result for other plants. Whereas 30.4% of patients showed serological sensitization to birch pollen extract, only 18.8% displayed positive specific IgE to Bet v 1. Clinical assessment revealed that most patients with AR were polysensitized and had perennial symptoms or symptoms also occurring during times other than tree flowering times. If the SPT panel is limited to testing birch only, 52.2% of patients in this subgroup would have been overlooked. CONCLUSION: Inconsistent SPT results in the birch homologous group may result from cross-reacting allergens or technical errors. If patients report convincing clinical symptoms despite negative results from a reduced SPT panel or inconsistent results for homologous allergens, SPT should be repeated, and molecular markers should be added to achieve a correct diagnosis.

Oral health in HPV-positive and HPV-negative patients with oropharyngeal squamous cell carcinoma.

This study compared oral health in oropharyngeal squamous cell carcinoma (OPSCC) patients with positive or negative human papillomavirus (HPV) status and analysed whether oral health was associated with survival. Patients referred for dental assessment prior to radio(chemo)therapy between 2009 and 2019 were included. Patient-related risk factors for OPSCC (alcohol, tobacco, HPV status), age, sex, treatment (primary treatment, intent), performance status, tumor/node/metastasis (TNM) staging, and oral health parameters (DMFT, periodontal status, teeth with/without root canal treatment and with/without periodontitis apicalis) were compared between HPV-negative and HPV-positive patients. Survival was assessed using Kaplan-Meier statistics. The effect of patient-related risk factors and oral health parameters was analysed by cox regression analyses (α=5%). A total of 119 patients (n=50 HPV-negative, n=69 HPV-positive) was included. HPV-positive patients showed more present teeth, a higher number of filled teeth, were less often edentulous and presented a lower DMFT compared to HPV-negative patients (padj.≤0.003). Among dentulous patients, HPV-positive patients showed more present teeth and fewer teeth with periodontitis apicalis lacking a root canal treatment (padj.≤0.036). Survival probability differed between groups (p=0.006) and trended towards being associated with HPV status, tobacco exposure, performance status, T stage, N stage, and the number of missing or filled teeth as well as the number of root canal treated teeth with periodontitis apicalis and the number of teeth with periodontitis apicalis lacking a root canal treatment (p≤0.077). However, only tobacco exposure, performance status, and the number of teeth with periodontitis apicalis lacking a root canal treatment in dentulous patients remained significant in the multivariate analyses (p≤0.047). HPV-negative patients with OPSCC showed a poorer oral health compared to HPV-positive patients, but survival was not associated with oral health.

A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate.

OBJECTIVE: In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre-tension in the annular ligament resulting in unsatisfactory hearing results. METHODS: In collaboration with MED-EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser-Doppler-Vibrometry, we measured the sound-induced velocity of the stapes footplate relative to a given acoustic stimulus. RESULTS: The new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane. CONCLUSION: This development is a further step toward a physiological reconstruction of the ossicular chain. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1717-1721, 2023.

The proto-oncogene TCL1A deregulates cell cycle and genomic stability in CLL.

Upregulation of the proto-oncogene T-cell leukemia/lymphoma 1A (TCL1A) is causally implicated in various B-cell and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, the molecular and cell biological consequences of, particularly nuclear, TCL1A are not fully elucidated. We observed here in mouse models of subcellular site-specific TCL1A-induced lymphomagenesis that TCL1A exerts a strong transforming impact via nuclear topography. In proteomic screens of TCL1A-bound molecules in chronic lymphocytic leukemia (CLL) cells and B-cell lymphoma lines, we identified regulators of cell cycle and DNA repair pathways as novel TCL1A interactors, particularly enriched under induced DNA damage and mitosis. By functional mapping and in silico modeling, we specifically identified the mitotic checkpoint protein, cell division cycle 20 (CDC20), as a direct TCL1A interactor. According to the regulatory impact of TCL1A on the activity of the CDC20-containing mitotic checkpoint and anaphase-promoting complexes during mitotic progression, TCL1A overexpression accelerated cell cycle transition in B-cell lymphoma lines, impaired apoptotic damage responses in association with pronounced chromosome missegregation, and caused cellular aneuploidy in Eµ-TCL1A mice. Among hematopoietic cancers, CDC20 levels seem particularly low in CLL. CDC20 expression negatively correlated with TCL1A and lower expression marked more aggressive and genomically instable disease and cellular phenotypes. Knockdown of Cdc20 in TCL1A-initiated murine CLL promoted aneuploidy and leukemic acceleration. Taken together, we discovered a novel cell cycle-associated effect of TCL1A abrogating controlled cell cycle transition. This adds to our concept of oncogenic TCL1A by targeting genome stability. Overall, we propose that TCL1A acts as a pleiotropic adapter molecule with a synergistic net effect of multiple hijacked pathways.

A mutation in ATP11A causes autosomal-dominant auditory neuropathy type 2.

Auditory synaptopathy/neuropathy (AS/AN) is a distinct type of sensorineural hearing loss in which the cochlear sensitivity to sound (i.e. active cochlear amplification by outer hair cells) is preserved whereas sound encoding by inner hair cells and/or auditory nerve fibers is disrupted owing to genetic or environmental factors. Autosomal-dominant auditory neuropathy type 2 (AUNA2) was linked either to chromosomal bands 12q24 or 13q34 in a large German family in 2017. By whole-genome sequencing, we now detected a 5500 bp deletion in ATP11A on chromosome 13q34 segregating with the phenotype in this family. ATP11A encodes a P-type ATPase that translocates phospholipids from the exoplasmic to the cytoplasmic leaflet of the plasma membrane. The deletion affects both isoforms of ATP11A and activates a cryptic splice site leading to the formation of an alternative last exon. ATP11A carrying the altered C-terminus loses its flippase activity for phosphatidylserine. Atp11a is expressed in fibers and synaptic contacts of the auditory nerve and in the cochlear nucleus in mice, and conditional Atp11a knockout mice show a progressive reduction of the spiral ganglion neuron compound action potential, recapitulating the human phenotype of AN. By combining whole-genome sequencing, immunohistochemistry, in vitro functional assays and generation of a mouse model, we could thus identify a partial deletion of ATP11A as the genetic cause of AUNA2.

Association between spatial distribution of leukocyte subsets and clinical presentation of head and neck squamous cell carcinoma.

Background: Interactions between tumor cells and cells in the microenvironment contribute to tumor development and metastasis. The spatial arrangement of individual cells in relation to each other influences the likelihood of whether and how these cells interact with each other. Methods: This study investigated the effect of spatial distribution on the function of leukocyte subsets in the microenvironment of human head and neck squamous cell carcinoma (HNSCC) using multiplex immunohistochemistry (IHC). Leukocyte subsets were further classified based on analysis of two previously published HNSCC single-cell RNA datasets and flow cytometry (FC). Results: IHC revealed distinct distribution patterns of leukocytes differentiated by CD68 and CD163. While CD68hiCD163lo and CD68hiCD163hi cells accumulated near tumor sites, CD68loCD163hi cells were more evenly distributed in the tumor stroma. PD-L1hi and PD-1hi cells accumulated predominantly around tumor sites. High cell density of PD-L1hi CD68hiCD163hi cells or PD-1hi T cells near the tumor site correlated with improved survival. FC and single cell RNA revealed high variability within the CD68/CD163 subsets. CD68hiCD163lo and CD68hiCD163hi cells were predominantly macrophages (MΦ), whereas CD68loCD163hi cells appeared to be predominantly dendritic cells (DCs). Differentiation based on CD64, CD80, CD163, and CD206 revealed that TAM in HNSCC occupy a broad spectrum within the classical M1/M2 polarization. Notably, the MΦ subsets expressed predominantly CD206 and little CD80. The opposite was observed in the DC subsets. Conclusion: The distribution patterns and their distinct interactions via the PD-L1/PD-1 pathway suggest divergent roles of CD68/CD163 subsets in the HNSCC microenvironment. PD-L1/PD-1 interactions appear to occur primarily between specific cell types close to the tumor site. Whether PD-L1/PD-1 interactions have a positive or negative impact on patient survival appears to depend on both the spatial localization and the entity of the interacting cells. Co-expression of other markers, particularly CD80 and CD206, supports the hypothesis that CD68/CD163 IHC subsets have distinct functions. These results highlight the association between spatial leukocyte distribution patterns and the clinical presentation of HNSCC.

Performance and self-perceived hearing impairment after cochlear implantation in Menière's disease.

OBJECTIVE: Evaluation of the self-perceived hearing impairment and performance after cochlear implantation in patients with definite Menière's disease (MD). PATIENTS AND METHODS: Seventeen unilaterally or bilaterally profoundly hearing-impaired patients suffering from MD who received a cochlear implantat (CI) were eligible for inclusion in this study. Their self-perceived hearing impairment using the short Speech Spatial and Qualities of Hearing Scale (SSQ12) as well as their performance in speech perception (German language Freiburger mono- and multisyllable test, Oldenburger sentence test) were compared with a best-matched control group of non-MD patients up to 24 months of follow-up. RESULTS: MD patients improved significantly in perception of monosyllables presented at 65 dBSPL, from preoperatively best aided 18.2% [2.4, 34.0] to 51.7% [39.4, 63.9] 1 year after cochlear implantation (mean [95% confidence interval]). Their performance approached the matched controls with 63.2% [55.7, 70.8]. Monosyllables presented at a lower intensity of 55 dBSPL revealed a significant underperformance of the MD patients (21.1% [12.6, 29.6]) in contrast to the non-MD controls (39.1% [30.9, 47.4]) 12 months post-CI. Self-assessed hearing disability was significantly more pronounced in MD patients with a mean total SSQ12 score of 3.6 [2.4, 4.9] in comparison to 6.1 [5.4, 6.8] of the matched non-MD controls after 12 months of cochlear implantation. CONCLUSION: Cochlear implantation substantially improves hearing capabilities in profoundly hearing-impaired patients with MD, but they tend to underperform in comparison to non-MD patients at least at lower sound pressure levels. This is likely one reason for the poorer self-assessed hearing function of cochlear implanted MD patients. LEVEL OF EVIDENCE: 3, retrospective, nonrandomized follow-up study.

The impact of tympanic membrane perforations on middle ear transfer function.

PURPOSE: Injury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear. METHODS: The middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, » of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated. RESULTS: The measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz. CONCLUSION: Size and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.

[Updated S2k AWMF guideline on obstructive sialadenitis]. / Aktualisierte AWMF-S2k-Leitlinie zur obstruktiven Sialadenitis.

The update of this guideline was an important step to define standards for the use of sialendoscopy and other emerging minimally invasive techniques for the therapy of sialolithiasis and other obstructive salivary gland diseases. The current actualization was necessary to adapt the diagnostic and therapeutic algorithms to the current scientific knowledge. In this article they are presented in a shortened version with a focus on conservative therapeutic measures which are especially relevant for daily practice.