[Endoscopic endonasal anterior skull base surgery : Presentation of a monocentric entity profile]. / Endonasal-endoskopische anteriore Schädelbasischirurgie : Darstellung eines monozentrischen Entitätenprofils.

BACKGROUND: Extended endoscopic endonasal surgery (EEES) is an essential part of treatment of various pathologies of the anterior skull base. In addition to significant improvements in the quality of life of affected patients and a lower complication profile compared to open skull base surgery, the therapeutic results are comparable if the indications are correct. MATERIALS AND METHODS: Data of all endoscopic endonasal skull base procedures performed at the University Skull Base Center Hamburg under the direction of the Department of Otorhinolaryngology between June 2018 and November 2022 were retrospectively collected. RESULTS: A total of 50 cases were identified. Of these, 56% (28/50) were malignant tumors, 24% (12/50) were benign pathologies with direct skull base involvement, and 20% (10/50) were anterior skull base defects with rhinoliquorrhea. In 96% (48/50) of cases, the preoperatively set goal of surgery (representative biopsy, complete resection, closure of the skull base defect) could be achieved. Complications grade III or higher according to Clavien-Dindo occurred in 4/50 cases. During the observation period, n = 5 olfactory neuroblastomas were diagnosed, all of which were exclusively and successfully operated on endoscopically. CONCLUSION: In recent years, the spectrum of endoscopically resectable pathologies of the anterior skull base has steadily expanded. In particular, midline-related tumors such as olfactory neuroblastoma or iatrogenic/idiopathic skull base defects with cerebrospinal fluid rhinorrhea are treated completely endoscopically with very good results. Nevertheless, there are also limitations to this technique. Due to high variance in the scope of frontobasal surgery, the extent, and the complex anatomy, as well as the overlapping responsibilities of the specialist disciplines, establishment of certified skull base centers and bundling of frontobasal surgery at these centers is highly relevant for quality assurance.

A Novel Diagnostic and Treatment Algorithm for Acute Mastoiditis in Children Based on 109 Cases.

BACKGROUND: Acute mastoiditis (AM) is a potentially life-threatening condition primarily affecting children. To date, there are no consistent criteria or valid guidelines for the diagnosis and treatment of pediatric AM. Therefore, this study evaluates the clinical course of AM in terms of clinical signs and treatment. In addition, a novel classification scheme for the disease and a treatment algorithm is being proposed. METHODS: Patient records over a 12-year period from a single center were reviewed to identify confirmed cases of AM in children. Data collected included clinical signs, body temperature, and infection parameters during the disease, as well as radiological imaging, antibiotics, and surgical as well as conservative treatment. In addition, a classification of the AM stages was established in accordance with the findings described and practical experience, consisting of four stages (1, mastoidal irritation; 2, mild AM; 3, advanced AM; 4, advanced AM and additional complications) with corresponding treatment recommendations. In the retrospective cohort, those AM cases that were treated alongside the classification were compared with the rest concerning clinical course and outcome. RESULTS: A total of 109 patients (mean age, 3.8 ± 3.8 years) were included. The main symptoms at hospital admission were auricular protrusion (n = 73; 67.0%), fever (n = 56; 51.4%) with a mean temperature of 38.3 ± 1.1°C, and otalgia (n = 28; 25.7%). The mean laboratory-tested levels of leukocytes and C-reactive protein at the time of hospital admission were 15.96 ± 8.7/nl and 59.6 ± 54.0 mg/L, respectively. During winter, there was a higher prevalence of AM, with peak hospital admissions in April (n = 22). The most common pathogen was Streptococcus pyogenes (32 cases). Treatment was purely conservative in four cases, whereas the remaining cases underwent surgery (41× grommet insertion, 64× plus mastoidectomy). The outcome was generally good, but in eight patients a second surgical procedure had to be performed as they showed signs of clinical deterioration. A total of 101 patients were treated according to the proposed algorithm, and all of which had a good outcome without the need for further interventions. CONCLUSION: Based on clinical experience in a large cohort of pediatric AM patients, a novel diagnostic and treatment algorithm has been developed and successfully tested in a retrospective cohort for AM in children to prevent further complications and to ease its management by pediatricians and otorhinolaryngologists in the emergency setting.

Outcomes following oropharyngeal squamous cell carcinoma resection and bilateral neck dissection with or without contralateral postoperative radiotherapy of the pathologically node-negative neck.

PURPOSE: There are no consensus guidelines regarding the postoperative treatment of the contralateral pathologically node-negative neck in oropharyngeal squamous cell carcinoma. This study aimed to determine if omission of postoperative irradiation of the contralateral pathologically node-negative neck affects oncological outcomes. METHODS: We retrospectively identified 84 patients with primary surgical treatment including bilateral neck dissection and postoperative (chemo-)radiotherapy (PO(C)RT). Survival was analyzed using the log-rank test and the Kaplan-Meier method. RESULTS: Patients showed no decrease in tumor-free, cause-specific (CSS), or overall survival (OS) when PO(C)RT of the contralateral pathologically node-negative neck was omitted. Increased OS was found in patients with unilateral PO(C)RT and especially an increased OS and CSS was found in unilateral PO(C)RT and in tumors arising from lymphoepithelial tissue. CONCLUSIONS: Omitting the contralateral pathologically node-negative neck appears to be safe in terms of survival and our retrospective study advocates further prospective randomized control de-escalation trials.

Impaired DNA double-strand break repair and effective radiosensitization of HPV-negative HNSCC cell lines through combined inhibition of PARP and Wee1.

Objectives: In head and neck squamous cell carcinoma (HNSCC), tumors negative for Human Papillomavirus (HPV) remain a difficult to treat entity and the morbidity of current multimodal treatment is high. Radiotherapy in combination with molecular targeting could represent suitable, less toxic treatment options especially for cisplatin ineligible patients. Therefore, we tested dual targeting of PARP and the intra-S/G2 checkpoint through Wee1 inhibition for its radiosensitizing capacity in radioresistant HPV-negative HNSCC cells. Materials and methods: Three radioresistant HPV-negative cell lines (HSC4, SAS, UT-SCC-60a) were treated with olaparib, adavosertib and ionizing irradiation. The impact on cell cycle, G2 arrest and replication stress was assessed through flow cytometry after DAPI, phospho-histone H3 and γH2AX staining. Long term cell survival after treatment was determined through colony formation assay and DNA double-strand break (DSB) levels were assessed through quantification of nuclear 53BP1 foci in cell lines and patient-derived HPV± tumor slice cultures. Results: Wee1 and dual targeting induced replication stress but failed to effectively inhibit radiation-induced G2 cell cycle arrest. Single as well as combined inhibition increased radiation sensitivity and residual DSB levels, with the largest effects induced through dual targeting. Dual targeting also enhanced residual DSB levels in patient-derived slice cultures from HPV-negative but not HPV+ HNSCC (5/7 vs. 1/6). Conclusion: We conclude that the combined inhibition of PARP and Wee1 results in enhanced residual DNA damage levels after irradiation and effectively sensitizes radioresistant HPV-negative HNSCC cells. Ex vivo tumor slice cultures may predict the response of individual patients with HPV-negative HNSCC to this dual targeting approach.

Is Vestibular Neuropathy Rather a Neuritis?

Background/objectives Vestibular neuritis (VN) is one of the most common causes of peripheral vestibular neuropathy. The goal of this study is to investigate the possible infectious causes of VN in a large cohort of patients. Material and methods In total, 98 consecutive VN patients were enrolled in this retrospective study over a four-year period (04/2015-04/2019). Diagnosis of VN was made by clinical examination and functional diagnostics. We focused on infectious causes such as neurotropic viruses and Lyme disease (LD) and evaluated infection parameters as well as the concomitant diseases. Results In this cohort, we found pathologically elevated leukocytes or C-reactive protein (CRP) levels, and/or acute herpes simplex virus (HSV) infection, cytomegalovirus (CMV) infection and LD in 42 patients (42.85%). Leukocytes were elevated in 39 of 98 patients (39.8%) and the mean count was 9717 ± 2991 /µl. The group comparison between patients with vestibular loss (n=42) and patients with vestibular hypofunction (n=45) revealed a significant difference in regard to elevated leukocytes (p=0.028). In total, 28 of 53 patients (52.8%) were positive for HSV immunoglobulin (Ig) G and four of 53 patients were positive for HSV IgM (7.5%). Six of 53 patients (11.3%) were positive for LD IgM. Conclusion In this cohort, there was a large number of VN patients with infectious signs; several patients tested positive for HSV and LD. Therefore we recommend testing VN patients not only for HSV but also for LD and other neurotropic viruses. This approach enables to complement the standard VN treatment with a specific treatment.

Endoscopic ear examination improves self-reported confidence in ear examination skills among undergraduate medical students compared with handheld otoscopy.

Objectives: Handheld otoscopy is the standard tool used to teach ear examination in undergraduate and postgraduate medical education. Previous studies have shown that the undergraduate teaching of ear examination with handheld otoscopes is inadequate, resulting in low self-reported levels of student confidence in their diagnostic skills. With the increase in popularity of endoscopic ear surgery, an increasing number of otolaryngologists are using endoscopes for office examinations of the ear due to the method's superior visualization and excellent image qualities. However, medical students usually do not receive exposure to endoscopic ear examination during their undergraduate curriculum. The aim of this study is to assess our preliminary experience with teaching endoscopic ear examination to undergraduate medical students. Methods: A two-hour-long pilot practical course on basic ear examination was administered to undergraduate medical students with little to no previous experience with ear examination. The course was designed to minimize the duration of campus attendance and patient contact during the COVID-19 pandemic. The course included theoretical didactics, exemplary digital endoscopic images and peer physical practice of ear examination with both a handheld otoscope and a 0-degree endoscope. At the end of the course, the students completed a survey questionnaire consisting of eight questions mainly relating to their subjective confidence level with ear examination using either handheld otoscopes or endoscopes and their overall preference for either examination tool. Results: Most students expressed a preference for ear examination with endoscopes over that with handheld otoscopes and reported an improved confidence level in their diagnostic ability with the former technique. The vast majority of students supported the teaching of endoscopic ear examination to future medical students. Conclusion: The findings of this pilot project report and survey study support the early exposure of novice medical learners to endoscopic ear examination, which may help improve the confidence and diagnostic skill of medical students with regard to ear examination. The findings may have implications for the undergraduate teaching of ear examination in the post-COVID-19 era.

Methods for Testing the Subjective Visual Vertical during the Chronic Phase of Menière's Disease.

The subjective visual vertical (SVV) evaluates the function of the utricle, which, in patients with Menière's disease (MD), can be affected by endolymphatic hydrops. This study aimed to determine the SVV in MD patients during the chronic phase of illness compared to healthy participants. The second aim was to compare the SVV measurement tools: the analog bucket test, digital bucket test, and C-SVV© goggles. The SVV scores differed significantly between MD patients and the control group for the analog bucket test (p < 0.001) and the C-SVV® goggles (p = 0.028), but no significance was shown when using the digital bucket test (p = 0.062). When comparing the analog bucket test and the C-SVV® goggles applying the calculated threshold (1.125° in analog bucket test, 2.5° in C-SVV® goggles), the bucket test showed higher accuracy (bucket test 73.84%, C-SVV® goggles 69.23%). When examining the influence of betahistine on SVV scores, there were no statistically significant differences in both the analog bucket test and C-SVV© goggles. We conclude that SVV test can be used as an additional tool to evaluate utricle function during the chronic phase of MD and that the analog bucket test produces the most reliable results. The intake of betahistine does not influence the perception of SVV.

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

PURPOSE: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. METHODS: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). RESULTS: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. CONCLUSIONS: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.

The mouse is the most widely used animal model in hearing research. Immunohistochemistry and immunofluorescent staining of murine cochlear sections have, thus, remained a backbone of inner ear research. Since many primary antibodies are raised in mouse, the problem of "mouse-on-mouse" background arises due to the interaction between the anti-mouse secondary antibody and the native mouse immunoglobulins. Here, we describe the pattern of mouse-on-mouse background fluorescence in sections of the postnatal mouse cochlea. Furthermore, we describe a simple double-blocking immunofluorescence protocol to label mouse cochlear cryosections. The protocol contains a conventional blocking step with serum, and an additional blocking step with a commercially available anti-mouse IgG blocking reagent. This blocking technique virtually eliminates the "mouse-on-mouse" background in murine cochlear sections, while adding only a little time to the staining protocol. We provide detailed instructions and practical tips for tissue harvesting, processing, and immunofluorescence-labeling. Further protocol modifications are described, to shorten the duration of the protocol, based on the primary antibody incubation temperature. Finally, we demonstrate examples of immunofluorescence staining performed using different incubation times and various incubation temperatures with a commercially available mouse monoclonal primary antibody. © 2020 The Authors. Basic Protocol: Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.

3D printing and characterization of human nasoseptal chondrocytes laden dual crosslinked oxidized alginate-gelatin hydrogels for cartilage repair approaches.

As cartilage is one of the few tissues in the human body that is not vascularized, the body has very limited capabilities to repair cartilage defects. Hence, novel condro-instructive biomaterials facilitating cartilage formation by implanted chondrocytes are required. In this work, an oxidized alginate-gelatin hydrogel system, alginate-di-aldehyde (ADA) and gelatin (GEL), was used to fabricate 3D printed grid-like structures for cartilage tissue engineering. Enzymatic and ionic crosslinking techniques using microbial transglutaminase (mTG) and divalent ions (CaCl2) were combined to ensure long-term stability of the 3D printed structures. Human nasoseptal chondrocytes were embedded in ADA-GEL prior to 3D printing. Cell viability, proliferation, and metabolic activity were analyzed after 7 and 14 days. The influence of the enzymatic crosslinking and the 3D printing process on the primary human chondrocytes were investigated. It was found that neither the 3D printing process nor the crosslinking by mTG impaired chondrocyte viability. The formation of the main cartilage-specific extracellular matrix components collagen type II and cartilage proteoglycans was shown by immunohistochemical staining. The combination of enzymatic and ionic crosslinking for the 3D printing of ADA-GEL hydrogels is therefore a promising approach for the 3D cultivation of primary human chondrocytes for cartilage tissue engineering.

Digital diaphanoscopy of the maxillary sinuses: A revival of optical diagnosis for rhinosinusitis.

PURPOSE: The non-invasive diagnosis of acute rhinosinusitis (ARS) remains an unresolved problem of modern otolaryngology. Analog diaphanoscopy of reduced transillumination (shading) could be enhanced by a digital image processing of the maxillary sinuses. By this means, the limited ergonomics of this safe and low-cost method can be overcome, and merits renewed the investigation. Here, we compared the diagnostic sensitivity and specificity of digital diaphanoscopy and computed tomography (CT) in detecting shading in the maxillary sinus. MATERIALS AND METHODS: We examined 103 adults using both digital diaphanoscopy of the maxillary sinus and native-phase cranial CT. We developed a scoring system for investigation of shading in the maxillary sinus using diaphanoscopy and compared the sensitivity and specificity with that of CT. Also, we documented a follow-up of acute rhinosinusitis. RESULTS: In diagnosing shading in the maxillary sinus, digital diaphanoscopy had a sensitivity of 86% and a specificity of 88%. Digital diaphanoscopy can be used not only in the screening of ARS but also for documentation of its course. CONCLUSION: This study supports the role of modern digital diaphanoscopy in the diagnosis of shading in the maxillary sinus, especially in patients with ARS when CT imaging is not recommended. The ergonomics of analog diaphanoscopy could be significantly improved for physicians and patients by the implementation of modern hardware and software components. Further development of the technique and the use of several discrete wavelengths will improve this method's sensitivity and specificity.

Comorbid Symptoms Occurring During Acute Low-Tone Hearing Loss (AHLH) as Potential Predictors of Menière's Disease.

Acute low-tone sensorineural hearing loss (ALHL) is a type of idiopathic sudden sensorineural hearing loss. ALHL is rarely a solitary condition but rather co-occurs with vertigo and tinnitus, being an element of contemporary diagnostic criteria for Menière's disease (MD). The goal of our present study was to determine the value of ALHL for the early diagnosis of MD in patients presenting in the emergency room with ALHL as a main complaint. The files of 106 patients with ALHL who were admitted to the emergency room over the period of 7 years and 104 patients with acute high- tone sensorineural hearing loss (AHHL) from the same period were included in this retrospective study. Forty ALHL patients presented with recurrent episode of hearing loss and 66 remaining patients presented with ALHL for the first time. Of the latter group, 25 patients gave consent for the follow-up. First, we analyzed the difference in the occurrence of tinnitus and vertigo between the ALHL and AHHL groups. In patients with ALHL, the incidence of vertigo with tinnitus and the number of recurrent episodes were statistically higher than in patients with AHHL. Next, we focused on the ALHL follow-up group (25 patients). In that group, two patients had all MD symptoms at presentation, 18 had ALHL and tinnitus and five ALHL only. Of 18 patients with ALHL and tinnitus at admission, five developed vertigo and thus the triad of Menière's disease. None of the five patients with AHLH as a sole symptom developed MD during the follow-up time but four of them have developed tinnitus. Patients with recurrent ALHL had significantly higher incidence of MD than the patients with first episode. We conclude that some patients who present with ALHL and concomitant tinnitus or have recurrent episodes of ALHL are more likely to develop Menière's disease than these patients, who present with ALHL as a sole symptom. Nonetheless, we recommend otological follow-up for all patients presenting with ALHL.

Effects of surgical treatment of hypertrophic turbinates on the nasal obstruction and the quality of life.

PURPOSE: Chronic hyperplasia of the inferior nasal concha is accompanied by a nasal obstruction; however, there is no standardised surgical treatment for this condition. Here, we compared the outcome of three surgical techniques frequently used to treat the hyperplasia of inferior turbinates: turbinectomy with lateralization, submucosal electrocautery and laser cautery additional to septoplasty. MATERIALS AND METHODS: One hundred and nine patients participated in this prospective randomized study upon signing written consent. The subjects were randomly assigned to one of three intervention groups: 1) submucosal turbinectomy with lateralization, 2) submucosal electrocautery or 3) laser cautery. All groups were followed-up for up to 6months after surgical intervention. During the four follow-up appointments, the outcomes were measured with the modified German version of Sino-Nasal Outcome Test 20 questionnaire. In addition, the nasal breathing and the absolute nasal flow rates and respective mucosal component were determined by the anterior rhinomanometry. RESULTS: Following surgery, the subjective and objective nasal obstruction decreased significantly in all three groups. Moreover, the subjective symptoms measured by modified Sino-Nasal Outcome Test 20 improved significantly, although there were some temporal differences between groups regarding subjective nasal obstruction, ear pressure, nasal discomfort, daytime fatigue, cough and dry mouth. The mucosal component of nasal congestion decreased significantly after surgery. CONCLUSIONS: All surgical techniques used to reduce the conchae mucosa led to a significant improvement in the objective and subjective nasal breathing and the quality of life. Septoplastic reduction proved to be of additional benefit.