Increase in acute mastoiditis at the end of the COVID-19 pandemic.

PURPOSE: Common respiratory infections were significantly reduced during the COVID-19 pandemic due to general protective and hygiene measures. The gradual withdrawal of these non-pharmaceutical interventions (NPI) was associated with a notable increase in these infections, particularly in pediatric and adult otorhinolaryngology. The aim of this retrospective monocentric study was to evaluate the impact of NPI during the COVID-19 pandemic on the incidence and severity of acute mastoiditis (AM). METHODS: Pre-pandemic clinical data of AM cases from 2011 to 2019 were compared with infection counts from January 2020 to June 2023 for seasonal periodicity, age-specific differences, pathogens, and complication rates in a German third-level hospital. RESULTS: Out of 196 patients with AM 133 were children, the majority between 1 and 5 years of age. Complications of AM, such as meningitis, brain abscess, and sinus vein thrombosis, were more common in adults (87%) than in children (17%). Morbidity and mortality rates were similar before, during and after the pandemic. Pneumococci were the most common pathogen in both age groups, with a post-pandemic cumulation of Streptococcus pyogenes infections in children. While pre-pandemic cases clustered in spring, seasonality was absent in all age groups during the main phase of the pandemic. The cessation of NPI caused a steep rise in AM cases in both age groups starting from December 2022. CONCLUSION: NPI during the COVID-19 pandemic reduced the incidence of AM. Their reversal led to a substantial increase in the incidence of AM during the post-pandemic period, which may be due to a general increase in viral respiratory infections and an insufficiently trained immune system.

[Emphysema after cochlear implantation - risk factors and therapeutic options]. / Emphyseme nach Cochlea-Implantation ­ Risikofaktoren und Therapieoptionen.

OBJECTIVE: In case of cochlear implantation seroma, hematoma, local wound infections or vertigo are rare but typical complications. In contrast, emphysema is seldom reported. They can occur after cochlear implantation both in the postoperative healing phase and years later. A therapeutic algorithm does not yet exist. METHODS: We report on 3 patients with subcutaneous emphysema in the area of the receiver-stimulator. An unsystematic review of the literature of cases with emphysema after cochlear implantation highlights possible risk factors and the therapeutic options. RESULTS: The 3 cases developed subcutaneous emphysema 2-11 month after cochlear implantation due to nose blowing or CPAP therapy in obstructive sleep apnea. The current literature reports another 35 cases of emphysema after cochlear implantation. Air insufflation via the Eustachian tube is the most frequently described cause. Diseases of the nose and sinuses, tube dysfunction and obstructive sleep apnea are potential risk factors. Pressure bandage, puncture, tympanic tubes, and surgical revision are common treatments. CONCLUSIONS: Most emphysema can be controlled by conservative methods such as pressure bandaging and behavioral instruction. Punctures should be avoided due to the risk of upcoming infections. The prophylactic use of antibiotics seems dispensable. Surgical revision should be considered especially in cases of pneumocephalus with suspected leakage in the dura. The coverage of the mastoidectomy by a bony cap can be precautious and beneficial in cases with risk factors.

[Adaption of the "Empty Nose 6 Item Questionnaire" (ENS6Q) into German language]. / Erstellung einer deutschen Version des "Empty Nose Syndrome 6 Item Questionnaire" (ENS6Q).

OBJECTIVE: The English "Empty-Nose-6-Item-Questionnaire" (ENS6Q) is a validated tool to assess subjective and disease-specific complaints of patients suffering from empty nose syndrome. The aim of this study was to create a validated German adapted version (GAV) of the ENS6Q. MATERIAL AND METHODS: The ENS6Q was translated into German language using a multistage process. Subsequently the translated questionnaire was completed twice by a group of patients suffering from empty nose syndrome (n = 36), a healthy control group (n = 77) and a group of patients with a symptomatic pathology of the nasal septum (n = 78). Additionally, the NOSE© questionnaire was completed twice by all groups. The ENS6Q was then examined regarding internal consistency, test-retest reliability, discriminant validity, sensitivity and specificity. RESULTS: The ENS6Q-GAV shows high internal consistency with Cronbachs α = 0,760 and α = 0,795. It also shows good test-retest reliability with an interclass correlation coefficient of 0,947 [0,930 - 0,961]. The ENS6Q-GAV discriminated significantly between empty nose syndrome patients and the control group. The receiver-operating characteristics curve showed a sensitivity of 83,3 % and a specificity of 88,3 % using a cut-off point of 8,5. The area-under-the-curve threshold score was 0,914 ± 0,029 [0,856 - 0,971]. CONCLUSIONS: The ENS6Q-GAV is the first validated disease-specific questionnaire in German to help identify patients suspected of developing ENS more reliably.

Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells.

Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine-mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC-derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB-603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA-mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment.

Laser surface modification of decellularized extracellular cartilage matrix for cartilage tissue engineering.

The implantation of autologous cartilage as the gold standard operative procedure for the reconstruction of cartilage defects in the head and neck region unfortunately implicates a variety of negative effects at the donor site. Tissue-engineered cartilage appears to be a promising alternative. However, due to the complex requirements, the optimal material is yet to be determined. As demonstrated previously, decellularized porcine cartilage (DECM) might be a good option to engineer vital cartilage. As the dense structure of DECM limits cellular infiltration, we investigated surface modifications of the scaffolds by carbon dioxide (CO2) and Er:YAG laser application to facilitate the migration of chondrocytes inside the scaffold. After laser treatment, the scaffolds were seeded with human nasal septal chondrocytes and analyzed with respect to cell migration and formation of new extracellular matrix proteins. Histology, immunohistochemistry, SEM, and TEM examination revealed an increase of the scaffolds' surface area with proliferation of cell numbers on the scaffolds for both laser types. The lack of cytotoxic effects was demonstrated by standard cytotoxicity testing. However, a thermal denaturation area seemed to hinder the migration of the chondrocytes inside the scaffolds, even more so after CO2 laser treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further modifications of the laser adjustments or the use of alternative laser systems might be advantageous for surface enlargement and to facilitate migration of chondrocytes into the scaffold in one step.

Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic.

BACKGROUND: The incidence of airborne respiratory infections fell as a result of the protective measures taken during the COVID-19 pandemic and rose again when these were stopped. In 2022, there was a notable rise in invasive group A streptococcal (iGAS) infections in many countries, including Germany. This rise was also reflected in the data of the university otorhinolaryngology department in Ulm, Germany. METHODS: This review is based on publications retrieved by a selective literature search on the rise of iGAS infections in Europe, with particular attention to the timing of disease onset, clinical presentation, pathogenic strains, and potential causes and risk factors. RESULTS: The rise in infections after the pandemic was especially marked among children up to age 10 and in older adults; in Germany, it affected all age groups equally, but predominantly persons older than 65. Rising prevalence figures were seen in Germany and elsewhere as early as the fall of 2022, outside the usual season, and peaked mainly in the first and second quarters of 2023. The increased incidence of iGAS-associated pneumonia was paralleled by that of viral airway infections and led to greater use of intensive-care measures for children. The main bacterial strain identified was emm1; a new variant (M1DK) played a role in Denmark, and an emm4 variant (M4NL22) became increasingly important in the Netherlands. In Germany, initial evidence suggested the predominance of M1UK. Increased antibiotic resistance was not found. CONCLUSION: The reduced confrontation of the immune system with pathogens during the pandemic, along with the increased incidence of viral airway infections immediately after it, apparently accounted for the exceptionally high post-pandemic rise in iGAS infections and the increase in invasive pulmonary diseases in Europe. Consistent vaccination programs against coincident respiratory viruses could reduce the burden of iGAS infections. The further extension of multinational surveillance programs with obligatory participation could aid in the detection of factors affecting the course of disease and the spread of new bacterial strains.

Enhanced cellular migration and prolonged chondrogenic differentiation in decellularized cartilage scaffolds under dynamic culture conditions.

Lesions of aural, nasal and tracheal cartilage are frequently reconstructed by complex surgeries which are based on harvesting autologous cartilage from other locations such as the rib. Cartilage tissue engineering (CTE) is regarded as a promising alternative to attain vital cartilage. Nevertheless, CTE with nearly natural properties poses a significant challenge to research due to the complex reciprocal interactions between cells and extracellular matrix which have to be imitated and which are still not fully understood. Thus, we used a custom-made glass bioreactor to enhance cell migration into decellularized porcine cartilage scaffolds (DECM) and mimic physiological conditions. The DECM seeded with human nasal chondrocytes (HPCH) were cultured in the glass reactor for 6 weeks and examined by histological and immunohistochemical staining, biochemical analyses and real time-PCR at 14, 28 and 42 days. The migration depth and the number of migrated cells were quantified by computational analysis. Compared to the static cultivation, the dynamic culture (DC) fostered migration of HPCH into deeper tissue layers. Furthermore, cultivation in the bioreactor enhanced differentiation of the cells during the first 14 days, but differentiation diminished in the course of further cultivation. We consider the DC in the presented bioreactor as a promising tool to facilitate CTE and to help to better understand the complex physiological processes during cartilage regeneration. Maintaining differentiation of chondrocytes and improving cellular migration by further optimizing culture conditions is an important prerequisite for future clinical application.

A contemporary review of "realistic" success rates after surgical closure of nasal septal perforations.

OBJECTIVE: The surgical closure of septal perforations is a challenging procedure. Various techniques exist. Each perforation proves that there is not the one precise procedure for all perforations. Nevertheless, success rates of about 90% are reported, although the procedure for closing the defect is challenging. Our goal was to evaluate the existing data. METHODS: We performed a contemporary review of published closure rates of septal perforations on order to compare the present results in the literature. The limitations of the respective studies were analyzed. RESULTS: We found closure rates from 30 to 100%. Numerous procedures were described and combined. Prospective studies comparing different techniques are missing. The follow-up time in studies was quite short or not even specified. Studies on long-term success rates are rare. CONCLUSION: The closure of septal defects is one of the most challenging rhinosurgical interventions. Closure rates ≥90% as described in literature seem relatively high. One reason might be short follow-ups and retrospective study designs. Frequently, precise information on the follow-up and the method of follow up is missing. Thoroughly designed prospective studies are absent. Longer follow-up times are associated with lower complete closure rates. A long-term success rate between 70 and 80% seems realistic.

Anthropometric Evaluation of Photographic Images Before and After Functional Nasal Surgery in Patients With Deviated Noses.

BACKGROUND: Numerous techniques for correction of deviated noses have been described. Nevertheless, surgical management is challenging even for experienced rhinosurgeons. Often, a "residual deformity" after functional septorhinoplasty (SRP) due to a deviated pyramid syndrome may remain. OBJECTIVE: Therefore, the purpose of this study was to determine how frequent functional SRP in patients with a deviated nose results in "successful" straightening of the external nose based on standardized angle measurements. Possible influences having a positive or negative effect on the surgical success were identified. METHODS: Photo documentation of 607 patients with deviated noses (304 women, 303 men, median age 30 years) before and after nasal surgery were retrospectively analyzed using standardized angle measurements. The pre- and postoperative photos of the faces were anthropometrically measured. The median follow-up was 6 months. RESULTS: A "straight" deviated nose (I-type) was present in 225 patients (37%), a C-shaped nose (C-type) in 382 patients (63%). More than 75% of the patients presented a facial asymmetry. Based on angle measurements alone, a total of 452 (75%) noses were straightened or postoperatively improved. 155 noses (25%) still showed a biometric deviation. The I- or C-type had no relevant influence on outcome. CONCLUSION: A purely biometric analysis of crooked noses is difficult and its importance is limited due to commonly pre-existing facial asymmetries. The risk of a "residual deviation" after rhinoplasty in patients with deviated noses must not be underestimated. This fact should be addressed as part of the informed consent. In particular, it should be mentioned that the surgical outcome can remain well below the patient's aesthetic expectations. Not rarely, a revision surgery may be necessary.

Application of a new computer-assisted robotic visualization system in cochlear implantation-Proof of concept.

BACKGROUND: Over the last decades conventional cochlear implant (CI) surgery has remained essentially unchanged. Nevertheless, alternative implantation techniques to further improve patient outcomes such as endaural implantation or robot-assisted surgery have been proposed in recent years. However, none of these have gained acceptance in clinical routine, thus confirming a demand for new developments. METHODS: Cochlear implant surgery was performed in two mastoid bones obtained from body donors using a novel hands-free exoscope. Advantages and disadvantages of the system were evaluated. RESULTS: In all cases, implantation of the electrode was feasible. The system allowed for hands-free movement and adjustment of the exoscope by the head-mounted display. Network connectivity of the system leaves room for improvement. CONCLUSION: The RoboticScope is an innovative tool and can be used supportively in conventional CI surgery in the experimental setting. Although operating the device requires a certain learning curve, the usability is intuitive for every ear surgeon.

Alpha-synuclein is present in dental calculus but not altered in Parkinson's disease patients in comparison to controls.

INTRODUCTION: In autopsy cases staged for sporadic Parkinson's disease (PD), the neuropathology is characterized by a preclinical phase that targets the enteric nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a source of potential (presymptomatic) PD biomarkers. METHODS: In this clinically based study, we examined the alpha-synuclein (αSyn) concentration in an easily accessible protein storage medium of the GIT, dental calculus, in 21/50 patients with PD and 28/50 age- and gender-matched controls using ELISA. RESULTS: αSyn was detectable in dental calculus and the median concentration in the control patients was 8.6 pg/mg calculus (interquartile range 2.6-13.1 pg/mg). αSyn concentrations were significantly influenced by blood contamination and samples with a hemoglobin concentration of > 4000 ng/mL were excluded. There was no significant difference of αSyn concentrations in the dental calculus of PD patients (5.76 pg/mg, interquartile range 2.91-9.74 pg/mg) compared to those in controls (p = 0.40). CONCLUSION: The total αSyn concentration in dental calculus is not a suitable biomarker for sporadic PD. Disease-related variants such as oligomeric or phosphorylated αSyn in calculus might prove to be more specific.

Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function.

One key point in the development of new bioimplant matrices for the reconstruction and replacement of cartilage defects is to provide an adequate microenvironment to ensure chondrocyte migration and de novo synthesis of cartilage-specific extracellular matrix (ECM). A recently developed decellularization and sterilization process maintains the three-dimensional (3D) collagen structure of native septal cartilage while increasing matrix porosity, which is considered to be crucial for cartilage tissue engineering. Human primary nasal septal chondrocytes were amplified in monolayer culture and 3D-cultured on processed porcine nasal septal cartilage scaffolds. The influence of chondrogenic growth factors on neosynthesis of ECM proteins was examined at the protein and gene expression levels. Seeding experiments demonstrated that processed xenogenic cartilage matrices provide excellent environmental properties for human nasal septal chondrocytes with respect to cell adhesion, migration into the matrix and neosynthesis of cartilage-specific ECM proteins, such as collagen type II and aggrecan. Matrix biomechanical stability indicated that the constructs retrieve full stability and function during 3D culture for up to 42 days, proportional to collagen type II and GAG production. Thus, processed xenogenic cartilage offers a suitable environment for human nasal chondrocytes and has promising potential for cartilage tissue engineering in the head and neck region.

Magnetic resonance imaging of the ear for patient-specific reconstructive surgery.

INTRODUCTION: Like a fingerprint, ear shape is a unique personal feature that should be reconstructed with a high fidelity during reconstructive surgery. Ear cartilage tissue engineering (TE) advantageously offers the possibility to use novel 3D manufacturing techniques to reconstruct the ear, thus allowing for a detailed auricular shape. However it also requires detailed patient-specific images of the 3D cartilage structures of the patient's intact contralateral ear (if available). Therefore the aim of this study was to develop and evaluate an imaging strategy for acquiring patient-specific ear cartilage shape, with sufficient precision and accuracy for use in a clinical setting. METHODS AND MATERIALS: Magnetic resonance imaging (MRI) was performed on 14 volunteer and six cadaveric auricles and manually segmented. Reproducibility of cartilage volume (Cg.V), surface (Cg.S) and thickness (Cg.Th) was assessed, to determine whether raters could repeatedly define the same volume of interest. Additionally, six cadaveric auricles were harvested, scanned and segmented using the same procedure, then dissected and scanned using high resolution micro-CT. Correlation between MR and micro-CT measurements was assessed to determine accuracy. RESULTS: Good inter- and intra-rater reproducibility was observed (precision errors <4% for Cg.S and <9% for Cg.V and Cg.Th). Intraclass correlations were good for Cg.V and Cg.S (>0.82), but low for Cg.Th (<0.23) due to similar average Cg.Th between patients. However Pearson's coefficients showed that the ability to detect local cartilage shape variations is unaffected. Good correlation between clinical MRI and micro-CT (r>0.95) demonstrated high accuracy. DISCUSSION AND CONCLUSION: This study demonstrated that precision and accuracy of the proposed method was high enough to detect patient-specific variation in ear cartilage geometry. The present study provides a clinical strategy to access the necessary information required for the production of 3D ear scaffolds for TE purposes, including detailed patient-specific shape. Furthermore, the protocol is applicable in daily clinical practice with existing infrastructure.

Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications.

Damage of cartilage structures in the head and neck region as well as in orthopedic sites are frequently caused by trauma, tumor resection, or congenital defects. Despite a high demand in many clinical fields, until today, no adequate cartilage replacement matrix is available for these fields of application. Materials that are clinically applied for joint cartilage repair still need optimization due to difficult intraoperative handling and risk of early mechanical damage. We have developed and applied a novel chemical process to completely decellularize and sterilize human and porcine cartilage tissues (meniscus cartilage and nasal septum) to generate a new type of bioimplant matrix. To characterize this matrix and to determine the effect of the decellularization process, the content of denatured collagen (w(D)) and the content of glycosaminoglycans (GAGs) (w(G)) were determined. Possible cytotoxic effects and cellular compatibility of the matrix in vitro have been examined by seeding processed cartilage biomatrices with human primary chondrocytes as well as murine fibroblasts (L929). Vitality and state of metabolism of cells were measured using MTS assays. Both cell types adhered to scaffold surfaces and proliferated. No areas of growth inhibition or cytotoxic effects were detected. New synthesis of cartilage-specific extracellular matrix was observed. By histological staining, electron microscopy, and µCT analysis, an increase of matrix porosity, complete cell elimination, and high GAG removal were demonstrated. Being from natural-origin, processed xenogenic and allogeneic cartilage biomatrices are highly versatile with regard to shape, size, and biomechanics, making them promising candidates for various biomedical applications.