[Increased rate of complications of pediatric acute otitis media and sinusitis in 2022/2023]. / Häufung von Komplikationen der akuten Otitis media und Sinusitis bei Kindern 2022/2023.

BACKGROUND: Acute mastoiditis and orbital complications of acute rhinosinusitis are among the most common complications of pediatric infections in otolaryngology. OBJECTIVE: The aim of this study was to investigate the frequency of pediatric acute mastoiditis in the setting of acute otitis media as well as pediatric orbital complications in the setting of acute rhinosinusitis. Data from before the pandemic were compared to data after the end of the COVID-19 restrictions. MATERIALS AND METHODS: Included were hospitalized children who presented with acute mastoiditis from acute otitis media or with orbital complications from acute rhinosinusitis during the period from April 2017 to March 2023. Compared were three periods using descriptive statistics: April 2017 to March 2020 (before the pandemic in Germany), April 2020 to March 2022 (during the contact restrictions of the pandemic), and April 2022 to March 2023 (after the contact restrictions were lifted). RESULTS: A total of 102 children (43 with acute mastoiditis, 42%, and 59 with orbital complications of acute sinusitis, 58%) were included. During the 2022/2023 period, more than twice as many children with acute mastoiditis and approximately three times as many children with orbital complications of acute rhinosinusitis were hospitalized compared to the average of the periods 2017/2018, 2018/2019, and 2019/2020. In the 2021/2022 period, the number of these patients was below the average of previous years. CONCLUSION: This year's seasonal cluster of upper respiratory tract infections is associated with a higher-than-average incidence of orbital complications and mastoiditis.

Intraindividual variability of the Eustachian tube function: a longitudinal study in a pressure chamber.

INTRODUCTION: The Eustachian tube (ET) is essential for fast and direct pressure equalisation between middle ear and ambient pressure. It is not yet known to what extent Eustachian tube function in healthy adults changes in a weekly periodicity due to internal and external factors. This question is particularly interesting with regard to scuba divers among whom there is a need to evaluate intraindividual ET function variability. METHODS: Continuous impedance measurement in a pressure chamber was performed three times at one-week intervals between measurements. Twenty healthy participants (40 ears) were enrolled. Using a monoplace hyperbaric chamber, individual subjects were exposed to a standardised pressure profile consisting of a 20 kPa decompression over 1 min, a 40 kPa compression over 2 min, and a 20 kPa decompression over 1 min. Measurements of Eustachian tube opening pressure (ETOP), opening duration (ETOD), and opening frequency (ETOF) were made. Intraindividual variability was assessed. RESULTS: Mean ETOD during compression (actively induced pressure equalisation) on the right side was 273.8 (SD 158.8) ms, 259.4 (157.7) ms, and 249.2 (154.1) ms (Chi-square 7.30, P = 0.026) across weeks 1-3. Mean ETOD for both sides was 265.6 (153.3) ms, 256.1 (154.6) ms, and 245.7 (147.8) ms (Chi-square 10.00, P = 0.007) across weeks 1-3. There were no other significant differences in ETOD, ETOP and ETOF across the three weekly measurements. CONCLUSIONS: This longitudinal study suggests low week-to-week intraindividual variability of Eustachian tube function.

Effects of freediving on middle ear and eustachian tube function.

INTRODUCTION: During descent in freediving there is exposure to rapidly increasing pressure. Inability to quickly equalise middle ear pressure may cause trauma to the ear. This study aimed to evaluate the occurrence of pressure-related damage to the middle ear and the Eustachian tube during freediving and to identify possible risk factors. METHODS: Sixteen free divers performed diving sessions in an indoor pool 20 metres' freshwater (mfw) deep. During each session, each diver performed four own free dives and up to four safety dives. Naso- and oto-endoscopy and Eustachian tube function tests were performed on the right and left ears before diving, between each session and after the last session. The otoscopic findings were classified according to the Teed classification (0 = normal tympanic membrane to 4 = perforation). Additionally, ENT-related complaints were assessed using a questionnaire. RESULTS: Participants performed 317 dives (on average 20 dives per diver, six per session). The average depth was 13.3 mfw. Pressure-related changes (Teed 1 and 2) were detected in 48 % of ears. Teed level increased significantly with an increasing number of completed sessions (P < 0.0001). Higher pressure-related damage (Teed 2) occurred in less experienced divers, was associated with significantly lower peak pressures in the middle ear and led to more ear-related symptoms. A preference for the Frenzel technique for middle ear pressure equalisation during freediving was shown. CONCLUSIONS: Pressure exposure during freediving had a cumulative effect on the middle ear. Factors such as diving depth, diving experience and number of diving sessions correlated with the occurrence of higher Teed levels.

[Mucoepidermoidcarcinoma - Importance in molecular pathology]. / Das Mukoepidermoidkarzinom ­ Bedeutung der Molekularpathologie.

Mucoepidermoid carcinoma is the most common primary salivary gland malignancy and its tumor grading has an important prognostic significance. The 5 year overall survival rate is significantly higher for low grade mucoepidermoid carcinomas than for intermediate grade and high grade mucoepidermoid carcinomas. The translocation of t(11;19)(q21;p13) with the resulting CRTC1-MAML2 transfusion appears to be of prognostic relevance in patients with mucoepidermoid carcinoma. The translocation is detectable in 38-82 % of all mucoepidermoid carcinomas. Study results have shown a significantly better prognosis for patients with fusion-positive mucoepidermoid carcinomas than fusion-negative mucoepidermoid carcinomas. The t(11;19)(q21;p13) translocation can be found more often in low and intermediate grade mucoepidermoid carcinomas than in high grade tumors of the same entity. Moreover, fusion positive mucoepidermoid carcinoma were found more frequently in younger patients, smaller tumors, lower tumor stages and less frequently lymph node and distant metastases. Up to now, the translocation has not been of therapeutic importance. In selected cases, the lack of t(11;19)(q21;p13) translocation might facilitate the decision towards further escalation of therapy. More studies will be necessary to evaluate the individual prognostic and therapeutic value of CRTC1-MAML2 transfusion.

Evaluation of the Parameter "Mean Impedance" for Representing Eustachian tube Functions During Pressure Increase and Decrease in Pressure Chamber Measurements.

HYPOTHESIS: The hypothesis of the study is that the mean impedance (MI) during compression and decompression provides additional information of the Eustachian tube (ET) function. BACKGROUND: The continuous impedance measurement in a pressure chamber can provide valuable information about the opening function of the ET. METHODS: Around 55 ear-healthy volunteers were examined in a pressure chamber. These were subjected to a decompression phase and a compression phase. The pressure change was constantly 20 kPa/min. Using evaluation software, the MI could be determined for both ears in each case for the phases of compression and decompression. RESULTS: In 49 participants, we could interpret the data successfully. On average, an output value (without pressure changes) of the impedance of 0.58 ±0.11 Pa on the right side and 0.43 ±â€Š0.1 Pa on the left side were measured. During decompression, 0.098 ±â€Š0.05 Pa (right) and 0.087 ±â€Š0.043 Pa (left) could be determined. For compression, values of 0.086 ±â€Š0.044 Pa on the right and 0.079 ±â€Š0.045 Pa on the left were detected. The retest reliability was higher with an intraclass correlation coefficient for the decompression MI of 0.833 than the 0.772 compression MI. CONCLUSIONS: It is possible to measure MI in healthy subjects during compression and decompression. This value represents a good average in terms of the pressure tolerance of the middle ear. In future, studies will be required to determine whether MI will be a useful parameter in differentiating normal and abnormal ET function.

Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma.

B lymphocytes are important players in immune responses to cancer. However, their composition and function in head and neck squamous cell carcinoma (HNSCC) has not been well described. Here, we analyzed B cell subsets in HNSCC (n = 38), non-cancerous mucosa (n = 14) and peripheral blood from HNSCC patients (n = 38) and healthy controls (n = 20) by flow cytometry. Intratumoral B cells contained high percentages of activated (CD86+), antigen-presenting (CD86+/CD21-) and memory B cells (IgD-/CD27+). T follicular helper cells (CD4+/CXCR5+/CD45RA-/CCR7-) as key components of tertiary lymphoid structures and plasma cells made up high percentages of the lymphocyte infiltrate. Percentages of regulatory B cell varied depending on the regulatory phenotype. Analysis of humoral immune responses against 23 tumor-associated antigens (TAA) showed reactivity against at least one antigen in 56% of HNSCC patients. Reactivity was less frequent in human papillomavirus associated (HPV+) patients and healthy controls compared to HPV negative (HPV-) HNSCC. Likewise, patients with early stage HNSCC or MHC-I loss on tumor cells had low TAA responses. Patients with TAA responses showed CD4+ dominated T cell infiltration compared to mainly CD8+ T cells in tumors without detected TAA response. To summarize, our data demonstrates different immune infiltration patterns in relation to serological TAA response detection and the presence of B cell subpopulations in HNSCC that can engage in tumor promoting and antitumor activity. In view of increasing use of immunotherapeutic approaches, it will be important to include B cells into comprehensive phenotypic and functional analyses of tumor-associated lymphocytes.

Analyzing eustachian tube function in patients with symptoms of chronical Eustachian tube dysfunction by pressure chamber measurements.

PURPOSE: The determination of Eustachian tube dysfunction (ETD) subtypes in daily routines is based on symptoms of the patient, otoscopy, nasopharyngoscopy, tympanometry, pure tone audiometry, and Valsalva's test, even though this clinical assessment is often not sufficient to clearly diagnose the subtype. In the study, we have evaluated the possibility of the determination of different subtypes of ETD by pressure chamber measurements. METHODS: In a single-person pressure chamber, we exposed 17 patients to pressure increases and decreases. The pressure profile of the continuous impedance of each tympanic membrane during the 5-min lasting measurement and the Eustachian tube (ET) pressure equilibration function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD), ET closing pressure (ETCP), and ET opening frequency (ETOF)-were documented and analyzed. RESULTS: By interpretation of the pattern of the continuous impedance of the tympanic membrane, we could relate patients to a subtype of ETD. Clearly identified by pressure chamber-based measurements could be patients with patulous ETD (n = 2) and baro-challenged-induced ETD (n = 4). The remaining 11 patients were classified as ETD not further classified. Patients diagnosed as patulous ETD did not show a pressure response on the tympanic membrane during the phases of pressure increase and decrease. In patients with baro-challenged-induced ETD, the measurement had to be interrupted due to the development of otalgia during progressive pressure increase as a result of insufficient possibility to equalize pressure variations. CONCLUSIONS: Pressure chamber-based measurements enable an objective and safe dynamic testing of the ET pressure equalization function in patients with ETD. In addition, via continuous impedance measurement, it is possible to identify patients with patulous ETD and baro-challenge-induced ETD. These results are a relevant preliminary work to identify and assess patients for different therapy options.

Assessment of the Importance of Tympanic Membrane Mechanoreceptors on Eustachian Tube Function Based on Pressure Chamber Measurements.

INTRODUCTION: Previously, it was demonstrated how the Eustachian tube (ET) opening function can be influenced by middle ear pressure and movement of the tympanic membrane via neural control. Mechanoreceptors on the tympanic membrane may be part of the afferent arc and could influence the middle ear pressure by activating the musculus veli palatini as part of a reflex. METHODS: In a hypo and hyperbaric pressure chamber, 17 participants (34 ears) were twice exposed to a standardized pressure profile of pressure decrease and increase. The ET function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD), and ET opening frequency (ETOF)-were determined before and after local anesthesia of the right tympanic membrane. RESULTS: After pressure exposure by pressure increase (active induced equalization) and pressure decrease (passive equalization) there was no significant difference between the mean value of ETOP, ETOD, and ETOF before and after local anesthesia of the right tympanic membrane on the right (anesthetized) or left side (not anesthetized). CONCLUSION: These results may lead to the hypothesis that tympanic membrane mechanoreceptors may play a minor role in regulating the ET function in humans.

Influence of repetitive diving in freshwater on pressure equalization and Eustachian tube function in recreational scuba divers.

INTRODUCTION: We investigated the effect of repetitive pressure exposure during freshwater dives on Eustachian tube function and the middle ear, assessed by the Eustachian tube function test (ETFT). METHODS: This prospective observational cohort study included 23 divers over three consecutive days of diving in freshwater lakes in Nordhausen, Germany. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The peak pressure difference between the R-tymp and the V-tymp (R-VdP) defined effectiveness of pressure equalization after Valsalva manoeuvres. We evaluated the change in compliance and peak pressure and correlated the results to the otoscopic findings and diving experience. RESULTS: Twenty-three divers performed 144 dives. Middle ear barotrauma was assessed using the Edmonds modification of the TEED scoring system. In the ETFT, the R-tymp peak pressure displayed a negative shift from day one to three (P = 0.001) and differed significantly between the experience groups (P = 0.01). R-VdP did not change significantly on any of the three days of diving (all P > 0.05). Participants without MEBt showed significantly lower R-tymp values than did those with barotrauma (P = 0.019). CONCLUSION: Repetitive pressure exposure during three consecutive days of freshwater diving led to a negative shift of the peak pressure in the middle ear. Less experienced divers showed significantly higher middle ear peak pressure and higher pressure differences after equalization manoeuvres. Higher middle ear peak pressure was also associated with a higher prevalence of barotrauma.

Influence of repetitive diving in saltwater on pressure equalization and Eustachian tube function in recreational scuba divers.

INTRODUCTION: We investigated in a prospective, observational trial the feasibility of using the Eustachian tube function test (ETFT) to measure the effect of repetitive pressure exposure during open seawater dives on Eustachian tube function. METHODS: The study included 28 adult divers during six consecutive days of diving in the Red Sea. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The R-tymp was obtained as 'baseline' peak pressure. After a Valsalva, the peak pressure should shift (positively), revealing a positive shift of the tympanic membrane. This pressure shift is defined here as R-VdP. The changes in compliance and peak pressure were recorded and correlated with otoscopic findings and diving experience. Middle ear barotrauma was scored using the Edmonds modified TEED scale. RESULTS: The 28 participants performed 437 dives. Positive shift of pressure in the middle ear was evident with significant changes from day one to day three (P < 0.0001). Divers with barotrauma showed significantly lower values of R-tymp peak pressure and significantly higher negative R-VdP, compared to divers with normal otoscopic findings (P < 0.05). Diving experience significantly correlated with R-tymp peak pressure and prevalence of middle ear barotrauma. CONCLUSION: Significant changes in middle ear pressure and pressure equalization from repeated pressure exposure in saltwater were seen using ETFT. Repetitive, multi-day diving led to significantly decreased compliance and increased R-tymp peak pressure (overpressure) in the middle ear. Most profound changes were observed in less and intermediate experienced divers.

MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas.

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs.25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2.In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance.

Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity.

Salivary gland cancer represents a heterogeneous group of malignant tumors. Due to their low incidence and the existence of multiple morphologically defined subtypes, these tumors are still poorly understood with regard to their molecular pathogenesis and therapeutically relevant genetic alterations.Performing a systematic and comprehensive study covering 13 subtypes of salivary gland cancer, next generation sequencing was done on 84 tissue samples of parotid gland cancer using multiplex PCR for enrichment of cancer related gene loci covering hotspots of 46 cancer genes.Mutations were identified in 22 different genes. The most frequent alterations affected TP53, followed by RAS genes, PIK3CA, SMAD4 and members of the ERB family. HRAS mutations accounted for more than 90% of RAS mutations, occurring especially in epithelial-myoepithelial carcinomas and salivary duct carcinomas. Additional mutations in PIK3CA also affected particularly epithelial-myoepithelial carcinomas and salivary duct carcinomas, occurring simultaneously with HRAS mutations in almost all cases, pointing to an unknown and therapeutically relevant molecular constellation. Interestingly, 14% of tumors revealed mutations in surface growth factor receptor genes including ALK, HER2, ERBB4, FGFR, cMET and RET, which might prove to be targetable by new therapeutic agents. 6% of tumors revealed mutations in SMAD4.In summary, our data provide novel insight into the fundamental molecular heterogeneity of salivary gland cancer, relevant in terms of tumor classification and the establishment of targeted therapeutic concepts.

Impact of xylomethazoline on eustachian tube function in healthy participants.

INTRODUCTION: The use of decongestants is common in otitis media eustachian tube (ET) dysfunction. However, the underlying mechanism and the type of action on the complex middle ear pressure equalization system are poorly understood. Here, by use of the pressure chamber, we investigated the impact of intranasal decongestive therapy (xylomethazoline) on ET function. MATERIALS AND METHODS: Thirty healthy participants (60 ears) were exposed to a predetermined profile of phases of compression and decompression in a hypobaric and hyperbaric pressure chamber. ET opening pressure, ET opening duration, ET opening frequency, and ET closing pressure were determined before and after intranasal application of xylomethazoline. RESULTS: A significantly higher number of ET openings (ET opening frequency) in passive equalization condition could be measured after application of decongestants than before. No significant difference could be found in the values of ET opening pressure, ET opening duration, and ET closing pressure parameters before in comparison with the values after application of xylomethazoline. CONCLUSION: We conclude that xylomethazoline might only have a minor effect during active and passive middle ear pressure equalization. Larger cohorts and targeted application of decongestants should be tested to confirm these preliminary data and to find new evidence on the effects of decongestants.

Valosin-containing protein (VCP/p97)-expression correlates with prognosis of HPV- negative oropharyngeal squamous cell carcinoma (OSCC).

Valosin-containing protein (VCP)/p97 has been shown to be associated with antiapoptotic function via activation of the nuclear factor-[Formula: see text]B (NF[Formula: see text]B) signaling pathway and with metastasizing of tumors in several studies. VCP is located on chromosome 9p13-p12, a region often deleted in oropharyngeal squamous cell carcinoma (OSCC). The clinical significance of VCP expression in OSCC however remains unclear. In this study, expression of VCP was determined in 106 patients (77 male (71.3%) and 31 female (28.7%); age-range: 34-79 years (mean age 57 years)) by immunohistochemistry and in a subset of 15 patients by quantitative PCR. HPV-DNA was detected by polymerase chain reaction and p16INK4a immunohistochemistry. The experimental findings were correlated with clinico-pathological data and survival parameters. 47.2% of all OSCC specimens were analyzed as negative or weak staining intensity for VCP. 52.8% of all specimens showed a high staining intensity for VCP. 73.1% of all patients were tested HPV-negative, 26.9% were HPV-positive. The 5-year disease-free and overall survival probabilities of all patients were 71.2% and 55.7%, respectively. No correlation could be found between HPV-status and VCP expression. VCP overexpression in HPV-negative patients was associated with significantly better 5-year disease-free survival (86.4% vs., 45.6%, p = 0.017). The level of VCP-intensity determined by immunohistochemistry could be an additional prognostic marker in HPV-negative OSCC. VCP expression seems not to correlate with the HPV-status.

Prevalence and risk factors for oral human papillomavirus infection in 129 women screened for cervical HPV infection.

BACKGROUND: Oncogenic human papillomaviruses (HPV) are known to be associated with carcinomas of the uterine cervix. Furthermore, current studies have shown that HPV-infection is also associated with a subtype of oropharyngeal cancers. In general, a sexual transmission of the viruses has been shown by numerous studies in the genital lesions. However, there are unknown factors regarding the prevalence and transmission of HPV in the oropharynx. The aim of this study was to evaluate HPV prevalence in the oropharynx in female participants with and without genital HPV infection. In addition, we analyzed risk factors for an oropharyngeal colonization with HPV in their sexual partners, too. METHODS: 129 Female participants were tested for presence of HPV-DNA by oral lavage, brush cytology of the tonsils and of the cervix. In addition, 15 male partners of these patients were included in the study. HPV-DNA was detected by PCR (polymerase chain reaction) amplification. For HPV-genotyping, PCR products were hybridized with type-specific digoxigenin-labeled oligonucleotide probes and discriminated into 14 high risk (HR) and 6 low risk (LR)-HPV types. The 129 female and 15 male participants were interviewed by a standardized questionnaire for socioeconomic details, drinking, smoking and sexual behaviours. RESULTS: 59 (45.7%) Female participants were negative for a genital HPV-infection. Of these women, 3 (5.1%) showed a positive HPV-PCR result (HR and LR) in the oropharynx. 70 (54.3%) Female participants were positive for a genital HPV infection. In this group, 4 (5.7%) had a positive HPV-detection (HR and LR) in the oral cavity and oropharynx. Female participants with cervical HPV-infection had no higher risk for HPV-detection in the oropharynx (not significant). The analysis of sexual risk factors revealed no specific risk factor for an oral HPV-infection. CONCLUSION: A correlation between cervical and oral colonization by HPV could not be demonstrated in our small cohort. Our limited data suggest that sexual transmission of HPV from the cervix uteri to the oropharynx is a rare and unlikely event.