Oral squamous cell carcinoma (OSCC) is increasingly common, with over 380,000 new cases annually. Despite its high incidence (6.0 per 100,000 males; 2.3 per 100,000 females) and poor prognosis, no molecular biomarkers exist for early detection. Non-invasive sampling could improve diagnosis and patient outcomes. This pilot study used RNA sequencing to identify significantly upregulated mRNA targets in swab samples from oral and oropharyngeal SCC patients and healthy probands. After filtering, four potential biomarkers were further validated in 79 samples using RT-qPCR. CombiROC analysis assessed diagnostic performance. Additional RT-qPCR on tumour and normal tissues and fluorescence staining in FFPE tumour sections evaluated expression at mRNA and protein levels. A panel of three markers (c-JUN, SFN, HSP90AB1) showed high diagnostic accuracy: 92.3% specificity, 92.3% sensitivity, and AUC of 0.91. Fluorescence staining confirmed significantly higher protein expression in tumour tissues, supporting RNA findings. The panel showed stronger diagnostic performance in men than in women. This study presents a promising non-invasive biomarker panel for oral and oropharyngeal SCC detection. Further validation in larger cohorts is needed to confirm diagnostic value and clarify sex specificity. The approach is adaptable to other tumour types and sample materials, supporting molecular diagnostics.

Abstract Background Meningiomas represent a common type of brain tumours and arise from the arachnoid cap cells which line the dural coverings of the brain. These predominantly benign tumours cause strong morbidity due to their intracranial location. Due to a lack of established pharmacological treatment approaches, surgery and radiotherapy remain the standard in clinical management of these tumours. Methods Here, we created a primary meningioma cell culture model and tested molecular compounds targeting key tumour-driving signalling pathways using cell viability assays and isobologram analysis. Results We found significant drug vulnerabilities within the meningioma-driving cell signalling network. Effective drugs included metformin, inhibitors of STAT3 and focal adhesion kinase (FAK), and the anti-inflammatory phytochemical sulforaphane, known as NRF2 pathway inducer and NFκB pathway inhibitor. Interestingly, FAK inhibitor Y15 and sulforaphane showed synergistic activity across cells of distinct meningioma patients, indicating this combination as a potential therapy approach. Conclusions Overall, we present a molecular targeting strategy for meningiomas that could pave the way for less invasive clinical management of these tumours and, as a result, help reduce patient mortality and morbidity. Metformin and sulforaphane both have FDA and EU pharmaceutical approval and thus could be repurposed promptly to establish a new meningioma therapy regimen.

PURPOSE:The assessment of endolymphatic hydrops (ELH) with specific MRI sequences underlines the ability to evaluate intralabyrinthine changes objectively and radiologically. The visualization of ELH by MRI allows correlations to be made with clinical patterns and supports the diagnosis of Ménière's disease (MD). Because MD cannot be assumed to be a static clinical condition, follow-up observations are of particular clinical interest. Our examination aimed to compare the grading of MRI-based ELH in patients over time, considering clinical symptoms and possible interventions. MATERIAL AND METHODS:Two MRI hydrops examinations and their gradings, from 11 patients with clinically definite MD, were compared in each case. The clinical pattern before and after conservative therapy or endolymphatic sac surgery was assessed over time using linear mixed regression. RESULTS:In 9 out of 11 patients, we observed an aligned trend in the MRI-based grading and hearing loss during an attack of MD. There was an increase in both parameters in eight patients. In one patient, an unchanged grading was observed. In one case, decrease was noted. In three cases there was a change of ELH, although the average hearing loss did not change. CONCLUSION:The MRI-based ELH may change during MD. Influencing variables and the correlation with clinical symptoms might be of great clinical interest regarding the success of therapy and the subjective complaints of patients. The different treatment options contribute to varying degrees to slowing the progression of MD.

Objective: Various orbital conditions (trauma, autoimmune thyroid disease, tumors, infections, congenital malformations) may lead to a consecutive increase in orbital cavity pressure resulting in orbital compartment syndrome (OCS). OCS is associated with acute loss of visual function and a high risk of permanent damage to the optic nerve (compressive optic neuropathy). Orbital decompression surgery (ODS) is a time-critical procedure that reduces pressure on the optic nerve, thereby improving visual function. The surgical management protocol for orbital decompression is not standardized and varies. Surgical techniques differ in orbital fat decompression, lateral canthotomy, and decompression of the medial orbital wall and floor. This retrospective study aims to evaluate surgery procedures and the outcome of visual function after orbital decompression surgery. Methods: In this retrospective study, we evaluated 28 patients (17 male, 11 female) with orbital compartment syndrome from May 2016 to October 2024. All patients underwent orbital decompression surgery as first-line treatment. Visual acuity (VA), diplopia, and ocular motility were analyzed pre- and postoperatively. Recovery was defined as postoperative improvement of vision, diplopia, and ocular motility. Linear and logistic regression analyses were used to assess the associations between clinically relevant risk factors and primary outcomes. Results: Orbital decompression surgery was performed with a median of 8.40 h (Q1: 4.80, Q3: 24.00) upon occurrence of symptoms. The average preoperative measured VA (logMAR) of the affected eye was 1.0. A total of 46% of the patients were preoperatively categorized as ”blind“ according to the WHO visual impairment categories. A total of 96% of the patients showed preoperative ocular motility impairment. Diplopia was preoperatively present in 46% of the patients. After orbital decompression surgery, postoperative visual acuity improved in 36% of the patients. Ocular motility improved by 67% and diplopia by 62% after ODS. The primary surgery technique was two-wall decompression in 68% (19/28) of the cases, followed by one-wall decompression (21%; 6/28), and three-wall decompression (11%; 3/28). Lateral decompression (82%; 23/28) and medial wall decompression (93%; 26/28) were the primary procedures performed. Orbital floor wall decompression was performed in only 14% (4/28) of the cases. Regression analysis revealed a statistically significant effect of preoperative measured vision on postoperative vision, while accounting for age, sex, and time to surgery. Conclusions: Orbital decompression surgery is the time-sensitive first-line treatment of acute visual function loss in OCS. Our data showed a postoperative improvement in visual acuity in 36% of the patients, along with considerable improvement rates in diplopia and ocular motility. The primary surgery technique was a two-wall decompression approach with lateral wall decompression and medial wall decompression. Center-specific timeline optimization of OCS patients is essential.

Background/Objectives: Surgical removal is the treatment of choice for cholesteatoma control. Depending on the size, the surgery involves partial resection of the ossicular chain and, if necessary, the bony skull base. Titanium foreign materials (prostheses, meshes) can be used to restore sound transmission and to cover larger defects of the skull base. After the operation, recurrence and residual control are necessary. This can be achieved by means of second-look surgery or an MRI examination with a non-EPI DWI sequence. Similarly to other metal implants, artifacts may occur in the image due to the titanium used. In this study, we assessed the magnitude of the MRI hardware differences induced by titanium prostheses and meshes and whether these differences could obscure cholesteatoma detection. Methods: 28 MRI examinations (T1-, T2-, non-EPI DWI sequences) in 14 males and 14 females (5.2-92.4 years) after cholesteatoma surgery and single-staged implantation of a PORP, TORP, or titanium mesh were considered. The size of the respective artifacts was measured, and the mean artifact sizes of the respective prosthesis types were compared. A second look surgery was performed in all cases due to the MRI result or clinical findings. Both were also compared. Results: Artifacts occurred in all titanium foreign bodies depending on the used MRI sequence (PORP, TORP, Mesh). We found a positive association between the size of the prosthesis and the size of the artifact. All subsequent second-look surgeries confirmed the MRI examinations according to a positive control for the presence of cholesteatoma. The detection rate was 82.1%. All false results were false negatives, and there were no positive results. Conclusions: Titanium material-related artifacts might influence the MRI detectability of recurrent cholesteatoma. Small cholesteatoma might be missed by an MRI-based follow-up. This finding supports the reevaluation of single-stage versus staged reconstruction modern approaches.

BackgroundAugmented reality (AR) glasses can be utilized for various medical applications. Primarily, a visual overlay on the optic screen offers additional operational information. A transfer of acoustic information via speech-to-text transcript using AR glasses presents a new non-surgical option to support patients with different forms of hearing loss. This study aimed to evaluate different AR glasses for speech-to-text transcription.MethodsWe compared four different AR glasses systems (Even Realities, G1; Meizu, MYVU IMIKI; XREAL, AIR, and Epson, Moverio 40) in terms of speech-to-text transcription, design, software, microphone and connection in this laboratory based study. Speech-capturing ability was tested using free-field numbers, monosyllables, and OLSA in quiet and in noise.ResultsThe AR systems achieved Freiburger monosyllabic speech recognition rates between 20 and 45% at 65 dB. OLSA in quiet results vary between 77 and 100%, with increases of +1.7 dB and +3.5 dB in noise. AR systems differ substantially in terms of design, software, microphone position, and connection. Proposed indication groups are given.ConclusionAR glasses provide a potential supportive tool for patients with specific indications suffering from hearing loss. The systems show limitations in challenging hearing situations.

Background/Objectives: Surgical removal is the treatment of choice for cholesteatoma control. Depending on the size, the surgery involves partial resection of the ossicular chain and, if necessary, the bony skull base. Titanium foreign materials (prostheses, meshes) can be used to restore sound transmission and to cover larger defects of the skull base. After the operation, recurrence and residual control are necessary. This can be done by means of second-look surgery or an MRI examination with a non-EPI DWI sequence. Similar to other metal implants, artifacts may occur in the image due to the titanium used. This study aimed to estimate MRI generated artifacts due to the titanium foreign material (prosthesis, mesh) to get insights in a possible limiting role for recurrent cholesteatoma detection. Methods: 28 MRI examinations (T1-, T2-, non-EPI DWI sequences) in 14 males and 14 females (5,2-92,4 years) after cholesteatoma surgery and single-staged implantation of a PORP, TORP, or titanium mesh were considered. The size of the respective artifacts was measured, and the mean artifact sizes of the respective prosthesis types were compared. A second look surgery was performed in all cases due to the MRI result or clinical findings. Both were also compared. Results: Artifacts occurred in all titanium foreign bodies depending on the used MRI sequence (PORP, TORP, Mesh). We found a positive association between size of prosthesis and size of artifact. All subsequent second-look surgeries confirmed the MRI examinations according to a positive control for the presence of a cholesteatoma. The detection rate was 82.1%. Conclusions: Titanium material-related artifacts might influence the MRI detectability of recurrent cholesteatoma. Small cholesteatoma might be missed by an MRI based follow up. Single or two staged reconstructive concepts after cholesteatoma surgery need to be discussed.

Background: Augmented reality (AR) glasses can be used for different medical indications. Primarily, a visual overlay on the optic screen offers additional operational information. A transfer of acoustic information via speech-to-text transcript using AR glasses presents a new non-surgical option to support patients with different forms of hearing loss. This study aimed to evaluate different AR glasses for speech-to-text transcription. Methods: We compared four different AR glasses (G1, MYVU, AIR, and Moverio 40) systems with a speech-to-text transcription regarding speech capturing, design, and software. Speech capturing ability was tested by free field numbers, monosyllabics, and OLSA in quiet and in noise. Results: The AR systems achieved Freiburger monosyllabic speech recognition rates between 20 % and 45 % at 65 dB. OLSA in quiet results varies between 77 % and 100 % and +1.7 dB and +3.5 dB in noise. AR systems differ substantially in terms of design and software. Proposed indication criteria are given. Conclusion: AR glasses offer a new treatment option for patients with selected indications. The systems show limitations in difficult hearing situations.

INTRODUCTION:Cochlear implantation is the treatment of choice for severe hearing loss and deafness. Cholesteatomas can cause this deafness. A frequently used procedure in the course of surgical rehabilitation is a subtotal petrosectomy combined with a cochlear implant. The clinical follow-up of residual cholesteatomas is related to the blind sac closure difficult. Cholesteatoma MRI sequence-related CI magnet artefacts make follow-up challenging. Recent developments in combining cochlear implants and necessary MRI examinations enable the assessment of the internal auditory canal and cochlea. The study aimed to develop a procedure for detecting cholesteatomas in patients with cochlear implants using magnetic resonance imaging (MRI). METHODS:Ex vivo MRI examinations were performed on five volunteers with fixed cochlear implants (Medel Synchrony) and swim caps. MRI examinations were performed at 1.5 T and 3 T using EPI, HASTE, and RESOLVE sequences (Siemens). The position of the implant was 12 cm distal to the external auditory canal, with anteversional head position of the volunteers in the MRI. RESULTS:Due to artefact effects, assessment of the ipsilateral and contralateral mastoid is not possible with EPI sequences and a cochlear implant. The combination of cholesteatoma-detecting MARS sequences (HASTE, RESOLVE), a distal implant position, and a specific head position allows the assessment of the ipsilateral mastoid. CONCLUSIONS:Postoperative cholesteatoma assessment after CI implantation and subtotal petrosectomy appears to be possible under 1.5 T and 3 T, considering the MRI sequence, implant position, and head position.

Introduction: The important factor in applying substances for inner ear therapy is the atraumatic execution, as well as effective concentration uniformly distributed in all regions of the cochlea within a reasonable time frame. This study investigates whether an additional cochlear opening (“second-hole technique”) can improve fluid distribution and reduce intracochlear pressure during dye delivery into the cochlear models and human petrous bone. Material and Methods: Three experimental setups were used: an uncoiled scala tympani model, a full-scale 3D-printed cochlear model, and a human petrous bone. In all cases, 1% methylene blue-stained saline was infused using a cochlear catheter (MED-EL, Innsbruck, Austria) through the round window. Intracochlear pressure was measured via fiberoptic pressure sensors inserted through a burr hole (artificial cochlear models) or at the lateral semicircular canal (human petrous bone). A second hole was made on the helicotrema in the inner ear models or at the oval window of the human petrous bone to examine the effect of a second hole on intracochlear pressure and fluid distribution. Dye distribution and intracochlear pressure were measured in 3D artificial models at two flow rates (0.2 and 0.4 mL/h). The intracochlear pressure were measured in the human petrous bone at a fixed rate (0.4 mL/h). Results: The use of a second hole significantly improved dye distribution in 3D models at both flow rates (p < 0.05) and led to earlier saturation-level distribution. Intracochlear pressure remained significantly lower and more stable in models with a second hole (p < 0.05). In human petrous bones, pressure fluctuation was reduced by the second hole, though pressure still increased over time. Conclusions: Using a second-hole technique leads to a faster, uniform level of dye distribution throughout the cochlear models, as well as a lower intracochlear pressure, which can be assumed to be an essential factor for hearing preservation during dye application.

More than 5% of the world's population suffers from disabling hearing loss. If the cause of hearing loss is unclear, it is referred to as idiopathic sudden sensorineural hearing loss (ISSNHL). After failure of standard treatment, the use of hearing aids or a cochlear implant is generally recommended. In this case, a 55-year-old patient was treated with cochlear implantation (CI) after ISSNHL and unsuccessful conservative therapy. Approximately 1 year after implantation and 7 years after the sudden hearing loss, subjective measurements revealed restoration of the hearing threshold.

Background: In most cases, intralabyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors varies but mostly affects the cochlea. Extirpation of the cochlear schwannoma, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intralabyrinthine schwannomas. Methods: In three patients, the TRD was used for the tumor removal of cochlear schwannomas. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach and an additional second turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-min procedure without any complications. An MRI control confirmed complete removal on the postoperative day in all cases. Conclusions: In vivo handling of the device confirmed straightforward handling for the tumor removal. MRI scanning showed complete removal of the tumor by the TRD.

More than 430 million people worldwide suffer from disabling hearing loss. This accounts for more than 5% of the world's population. According to WHO estimates, this number will rise to 700 million people by 2050.1 Fitting a cochlear implant is the treatment of choice for severe hearing loss. Newer cochlear implant systems enable MRI examinations, which produce strong magnetic fields, to be carried out with virtually no complications. To evaluate the effects of magnetic fields on the human cochlea, we sent a questionnaire to patients who received a cochlear implant in our clinic. Of 480 patients contacted, 95 patients responded. 62 patients reported having received an MRI. Twenty-two patients (35%) recalled hearing something on the implanted side during the MRI scan, whereas 40 (65%) did not hear anything. The auditory sensations ranged from humming (6), hissing (8) and a low tones (1) to high tones or beeping (7). Eight patients reported hearing something for the entire duration of the MRI, while others (12) only heard something for a short time. In 12 patients the sound disappeared after examination. Unfortunately, 5 patients who heard something did not answer this last question. In addition, ten patients reported dizziness, with the dizziness being continuous in three patients and lasting a few seconds or minutes in seven patients. MRI-generated stimulation of the labyrinth in CI users is not an uncommon effect of radiological examination. Animal experimental approaches pursue a therapeutic benefit of this effect (Lee et al., 2022)

Einleitung Mit einer Häufigkeit von 0,6% liegt bei Patienten mit Schwindelsymptomatik eine Bogengangsdehiszenz als Ursache zugrunde (1). Für HNO-Ärzte stellt sie eine wichtige Differentialdiagnose bei Patienten mit vestibulocochleären Symptomen dar. Am häufigsten liegt eine Dehiszenz des superioren Bogengangs vor. Klinische Symptome können in Form von Schwindel bei Durchführung eines Vasalva Manövers oder beim Niesen auftreten. Des Weiteren kann sie sich durch Autophonie, pulsierenden Tinnitus, Ohrdruck, sowie eine Schallleitungsstörung auf der betroffenen Seite bemerkbar machen. Der Schwindel hält häufig wenige Sekunden bis Minuten an und stellt daher eine wichtige Differentialdiagnose zum BPLS dar. Therapie der Wahl ist eine transmastoidale oder über die mittelere Schädelgrube erfolgte Bogengangsokklusion oder eine Okklusion des runden Fensters.

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting strategies are desperately needed, and a previous report indicated the triggered differentiation of HPV-negative HNSCC cells to confer therapeutic benefits. Using patient-derived tumor cells, we created a similar HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-Seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like in vitro differentiation occurs in human tissue. We are the first to report that carcinoma cells can undergo a triggered myocyte-like differentiation, and our study suggests that the targeted differentiation of HPV+ HNSCCs might be therapeutically valuable.

Abstract Head and neck squamous cell carcinoma (HNSCC) represents a highly malignant disease and death rates remain at approximately 50% for decades. Thus, new tumor-targeting treatment strategies are desperately needed. In a previous study, we dissected human papillomavirus (HPV)-negative HNSCC cell differentiation via cornification and detected an epigenetically determined loss of cell malignancy. Analyzing the mechanisms underlying the differentiation of HNSCC cells may identify targets for anti-tumor therapy. Using patient-derived tumor cells, we created an HNSCC differentiation model in HPV+ tumor cells. Similar to HPV- cells, we observed a loss of malignant characteristics in HPV+ cell cultures in differentiating cell culture conditions including irregular enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. Even though cornification was detected in HPV+ tumor cell cultures and HPV+ FFPE tumor tissue sections, cornification was not induced during HPV+ cell differentiation. Instead, RNA-seq and subsequent Gene Ontology analysis showed myocyte-like differentiation with upregulation of markers of myofibril assembly including TPM1, TAGLN, and ACTA1. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers, reminiscent of myoblast-lineage cells. Moreover, multi-marker immunofluorescence analysis of HPV+ tumor tissue sections revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like differentiation observed in vitro also occurred in human tissue. Normal tissue displayed a co-expression of TPM1, TAGLN, and ACTA1 in differentiating keratinocytes between the basal cell layer and the fully differentiated corneocytes. This shows that the expression of myocyte-lineage markers is reflected in differentiating non-malignant mucosal tissue. Our study suggests that the targeted differentiation of tumor cells might be therapeutically valuable in HPV+ HNSCCs as well. Citation Format: Sarah Gendreizig, Laura Martinez-Ruiz, Javier Florido, Alba López-Rodríguez, Harkiren Pabla, Frank Brasch, Germaine Escames, Tobias Busche, Holger Sudhoff, Lars U. Scholtz, Ingo Todt, Felix Oppel. Differentiation of human papillomavirus-positive head and neck squamous cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5818.

Hintergrund Die physiologische Funktion der Eustachischen-Röhre besteht in einer Reinigungs- und Belüftungsfunktion des Mittelohres. In Folge einer pathologischen Tubenbelüftung können chronische Mittelohrentzündungen, Cholesteatome und chronische Funktionsstörungen der Tube selbst entstehen. Therapeutisch stehen neben konservativen Verfahren die Durchführung von Paukendrainagen und Tubendilatation zur Verfügung. Die Ballonkatheter basierte Tubendilatation ist ein hocheffektives Verfahren zur Behandlung chronisch obstruktiver Tubenfunktionsstörungen. Bezüglich der Anwendung orientiert sich das Verfahren an standardisierten anatomischen Größenverhältnissen. Ziel dieser Studie war es, zu einer Einschätzung der generellen Kompatibilität des Verfahrens mit den anatomischen Verhältnissen der Tube mittels einer transtympanal visuellen Beurteilung zu kommen und hieraus Handlungsempfehlungen abzuleiten.

Einleitung Das intrakranielle Vestibularis-Schwannom (VS) ist ein gutartiger Tumor, der in der Regel aus den Schwannomzellen des VIII. Hirnnervs entspringen. In 94% der Fälle geht er mit einer sensorisch-neuralen Schwerhörigkeit (SNHL) einher, meist auf der ipsilateralen Seite. Jüngste Studien legen nahe, dass das Ergebnis der SNHL eher mit den vom Tumor abgesonderten Botenstoffen als mit der Größe des Tumors zusammenhängt. Interessanterweise haben nur wenige Studien auch eine Auswirkung von einseitigem VS auf das Hörvermögen der kontralateralen Seite beobachtet, was darauf hindeuten könnte, dass die vom Tumor stammenden Substanzen nicht nur auf das ipsilaterale Ohr wirken. Unser Ziel war es, das kontralaterale Hörvermögen in prä- und postoperativen VS-Fällen zu vergleichen und festzustellen, ob es sich nach der Behandlung verbessert.