The association of COVID-19 pandemic with the increase of sinogenic and otogenic intracranial infections in children: a 10-year retrospective comparative single-center study.

OBJECTIVE: Otitis media and sinusitis are common childhood infections, typically mild with good outcomes. Recent studies show a rise in intracranial abscess cases in children, raising concerns about a link to COVID-19. This study compares a decade of data on these cases before and after the pandemic. METHODS: This retrospective comparative analysis includes pediatric patients diagnosed with otitis media and sinusitis, who later developed intracranial abscesses over the past decade. We collected comprehensive data on the number of cases, patient demographics, symptoms, treatment, and outcomes. RESULTS: Between January 2013 and July 2023, our center identified 10 pediatric patients (median age 11.1years, range 2.2-18.0 years, 60% male) with intracranial abscesses from otitis media and sinusitis. Of these, 7 cases (70%, median age 9.7 years, range 2.2-18.0 years) occurred since the onset of the COVID-19 pandemic, while the remaining 3 cases (30%, median age 13.3 years, range 9.9-16.7 years) were treated before the pandemic. No significant differences were found in otolaryngological associations, surgical interventions, preoperative symptoms, lab findings, or postoperative antibiotics between the two groups. All patients showed positive long-term recovery. CONCLUSION: This study reveals 5-fold increase of pediatric otogenic and sinogenic intracranial abscess cases in the last three-years since the onset of the COVID-19 pandemic. While further investigation is needed, these findings raise important questions about potential connections between the pandemic and the severity of otitis media and sinusitis complications in children. Understanding these associations can improve pediatric healthcare management during infectious disease outbreaks.

Long-term outcome of patients with Ménière's disease following cochlear implantation: a comprehensive outcome study with validated assessment tools.

PURPOSE: Patients suffering from Ménière's disease (MD) experience vertigo, and impairments in hearing and quality of life (QoL). This study aims to investigate the impact of cochlear implantation (CI) on various aspects affecting patients with MD. METHODS: A single tertiary centre's CI database for CI recipients with MD between 2014 and 2022 was screened retrospectively. Hearing, vertigo, tinnitus symptoms, and hearing-related QoL were assessed. Pre- and postoperative hearing tests in conjunction with subjective outcome measures by visual analogue scale (VAS) and validated tools such as the Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI) and Nijmegen Cochlear Implant Questionnaire (NCIQ), as well as the assessment of the pre- and postoperative Functional Level Scale (FLS) were examined. RESULTS: Eleven ears were included (median age: 59 years at implantation). Following implantation, there was a significant enhancement in Word Recognition Scores at sound levels of 65 dB and 80 dB compared to before treatment (preop vs. 12 months postop: p = 0.012). However, no significant enhancement was observed for 50 dB. MD-related impairments improved significantly postoperatively, as measured by the VAS (vertigo: p = 0.017; tinnitus: p = 0.042), DHI (p = 0.043), THI (p = 0.043) and NCIQ (p < 0.001). The FLS improved significantly (p = 0.020). CONCLUSION: CI has positive effects on all areas examined in our cohort. However, discrimination of speech at low sound pressure levels remained problematic postoperatively. In patients suffering from MD, the prioritized treatment goals include not only improved hearing but also the rehabilitation of vertigo and tinnitus, as well as the enhancement of QoL. Validated instruments are useful screening tools.

[Validity of the German Menière's Disease Patient-Oriented Symptom Severity Index]. / Validierung des deutschsprachigen Menière's Disease Patient-Oriented Symptom Severity Index.

BACKGROUND: The MD POSI is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients with Menière's disease (MD). OBJECTIVES: Validity and reliability of the German translation of the MD POSI. MATERIAL AND METHODS: Prospective data analysis of a patient group with vertigo (n = 162), which was treated in the otorhinolaryngology of a University Hospital from 2005-2019. A clinical selection was made according to the new Bárány classification in a "definite" and "probable" Menière's disease. HRQoL was assessed using the German translation of the MD POSI, the Vertigo Symptom Score (VSS) and the Short Form (SF-36). Reliability was measured by Cronbach's α and test-retesting after 12 months and again 2 weeks later. Content and agreement validity were examined. RESULTS: Cronbach α values greater than 0.9 indicated good internal consistency. There was no statistically significant difference from baseline to 12 months, except for the subscore "during the attack". There were significant positive correlations between the VSS overall/VER/AA and the overall index of the MD POSI and negative significant correlations with the SF-36 domains physical functioning, physical role functioning, social functioning, emotional role functioning, mental well-being. There were low SRM (standardized response mean) values below 0.5. CONCLUSIONS: The German translation of the MD POSI is a valid and reliable instrument to evaluate the impact of MD on patients' disease-specific quality of life.

Balloon Eustachian Tuboplasty (BET) in Children: A Retrospective Multicenter Analysis.

OBJECTIVE: Generation of pilot data for planning of prospective BET-studies for treatment of dilatory Eustachian tube (ET) dysfunction in children. STUDY DESIGN: Retrospective multicenter analysis. SETTING: Nine ENT departments at tertiary care teaching hospitals. PATIENTS: 4-12-year-old children with chronic otitis media with effusion (COME) for more than 3 months or more than 3 episodes of acute otitis media during the last year, having failed standard surgical therapy at least once. INTERVENTION: BET with or without paracentesis, ventilation tube insertion, or tympanoplasty. MAIN OUTCOME MEASURES: Tympanic membrane appearance, tympanometry, and hearing threshold. RESULTS: Two hundred ninety-nine ETs of 167 children were treated. Mean age was 9.1 years (95% confidence interval [95% CI]: 8.7-9.4 yr). In 249 ears (83.3%), COME and/or retraction of the tympanic membrane were the indication for BET. Median hearing threshold was 20 dB HL (95% CI: 0-46 dB). One hundred fifty-five ears (51.8%, 95% CI: 46.1-57.4%) showed a tympanogram type B. Treatment consisted of BET without other interventions ("BET-only") in 70 children, 128 ears. Median length of follow-up for 158 (94.6%) children was 2.6 months (95% CI: 0.3-16.1 mo). After treatment, the tympanic membrane appeared normal in 196 ears (65.6%, 95% CI: 60.0-70.8%, p < 0.001). Median hearing threshold improved to 10 dB HL (95% CI: 0-45 dB, p < 0.001). Tympanograms shifted toward type A and C (type A: 39.1%, 95% CI: 33.7-44.7, p < 0.001). These improvements were also observed in subgroup analyses of "BET-only" treatment and the indication of "COME" respectively. CONCLUSION: BET is improving a variety of dilatory ET dysfunction-related ear diseases in children. This study provides detailed data for design and planning of prospective studies on BET in children.

Cervicofacial and mediastinal emphysema after balloon eustachian tuboplasty (BET): a retrospective multicenter analysis.

PURPOSE: Balloon Eustachian tuboplasty (BET) is a new treatment modality addressing chronic obstructive dysfunction of the Eustachian tube (ET). So far, BET has been deemed a safe procedure under general anesthesia with only minor adverse effects. However, individual cases of postoperative emphysema have been reported. In the present retrospective multicenter analysis we determined the incidence rate of this potentially life threatening complication after BET. METHODS: In total we collected data from 3,670 BET procedures performed on 2,272 patients in four tertiary care ENT departments. RESULTS: Ten cases of postoperative cervicofacial emphysema were documented, whereas only in 3 of them a pneumomediastinum was developed. None of the affected patients developed at any time serious clinical signs or symptoms besides cutaneous crepitations. A complete resolution and recovery of the emphysema occurred in all patients under antibiotic prophylaxis and abstinence from Valsalva maneuver within the first 2-6 postoperative days. CONCLUSIONS: Possible causes for the development of these postinterventional emphysemas are considered to be mucosal injuries of the ET during manipulations for the correct position of the insertion instrument, through a "kinking" of the balloon catheter or even due to the relative rigid catheter itself, although its form is regarded to be atraumatic. The complication rate of postoperative emphysema was 0.27% (95% CI 0.13-0.50%). The above facts in addition to only minor and transient overall complications after BET reported in literature, can label this procedure as a safe treatment with a low risk profile.

Changes in responsiveness of rat spiral ganglion neurons to neurotrophins across age: differential regulation of survival and neuritogenesis.

Developmental changes in responsiveness of rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were examined using an explant culture system. Spiral ganglion (SG) explants at embryonic Day 18 (E18), postnatal Day 0 (P0), P5, P10 and P20 were cultured with the addition of either NT-3 or BDNF at various concentrations (0.1-100 ng/ml) and analyzed the dose-response characteristics of three parameters: SGN survival, the number of neurites emanating from the explants and the length of neurite extension. In E18 cultures, SGN survival and neurite number were enhanced more strongly by NT-3 than by the BDNF. As the explants became more mature, the effects of NT-3 decreased, whereas those of BDNF increased, peaking at P0. Although the intrinsic capacity of SGNs to produce and extend neurites declined considerably by P20, they still retained the capacity to respond to both NT-3 and BDNF. These temporal patterns in responsiveness of SGNs to neurotrophins correspond well to the expression pattern of the two neurotrophins in cochlear sensory epithelium in vivo and also correlate with the time course of developmental events in SGNs such as cell death and the establishment of mature hair cell innervation patterns.

Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM).

Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion.

CC chemokine ligand 3 overcomes the bacteriocidal and phagocytic defect of macrophages and hastens recovery from experimental otitis media in TNF-/- mice.

Innate immune mechanisms are crucial in defense against bacterial illnesses in humans, as evidenced by abnormal antibacterial responses due to defects in TLR signaling, seen in children with MyD88 or IL-1R-associated kinase 4 deficiency. Otitis media (OM) is the most common disease of childhood, and the role of innate immune molecules in this disorder remains unclear. In a murine model of OM, we show that, in the absence of TNF, a key effector of innate immunity, this disease is prolonged after middle ear infection with nontypeable Haemophilus influenzae (NTHi). In the absence of TNF, mice fail to upregulate both TLRs and downstream genes and proteins, such as CCL3, resulting in defects in both inflammatory cell recruitment and macrophage function. Peritoneal macrophages of mice lacking TNF have a diminished ability to phagocytose and kill NTHi, and this defect is partially corrected in vitro by exogenous rTNF. Addition of rCCL3 alone or in combination with rTNF restores phagocytosis and killing by TNF-deficient macrophages to that of unstimulated wild-type macrophages. In vivo administration of rCCL3 to animals deficient in TNF fully restores the ability to control OM due to NTHi, whereas a CCL3-blocking Ab impaired the ability of wild-type mice to recover from OM. Thus, CCL3 is a potent downstream effector of TNF-mediated inflammation in vitro and in vivo. Manipulation of CCL3 and/or TNF may prove to be effective therapeutic approaches in OM or other conditions associated with defective TNF generation.

Myeloid differentiation primary response gene 88 is required for the resolution of otitis media.

BACKGROUND: Signaling defects in the Toll-like receptor (TLR) pathway, such as interleukin-1 receptor-associated kinase 4 deficiency, highlight the prominence of TLR signaling in the defense against bacterial disease. Because myeloid differentiation primary response gene 88 (MyD88) can transduce signals from almost all TLRs, we studied its role in otitis media (OM), the most common upper respiratory tract bacterial infectious disease in young children. METHODS: The middle ears (MEs) of wild-type (WT) and MyD88(-/-) mice were inoculated with nontypeable Haemophilus influenzae (NTHi). ME infection and inflammation were monitored for 21 days after surgery. Bone marrow-derived macrophages from WT and MyD88(-/-) mice were infected with NTHi in vitro to assess their interaction with bacteria. RESULTS: In WT mice, MyD88 expression was detected in the ME stroma at baseline. MyD88(-/-) mice displayed prolonged ME mucosal thickening and delayed recruitment of neutrophils and macrophages. Although WT mice cleared NTHi within 5 days, viable NTHi were isolated for up to 21 days in MyD88(-/-) mice. The interaction between macrophages and NTHi was significantly altered in MyD88(-/-) mice. CONCLUSIONS: In this mouse model, MyD88-mediated signaling was important for clearance of infection and resolution of inflammation in acute OM due to NTHi. The role played by innate signaling in children susceptible to chronic or recurrent OM deserves further study.

Laminin and fibronectin modulate inner ear spiral ganglion neurite outgrowth in an in vitro alternate choice assay.

Extracellular matrix (ECM) molecules have been shown to function as cues for neurite guidance in various populations of neurons. Here we show that laminin (LN) and fibronectin (FN) presented in stripe micro-patterns can provide guidance cues to neonatal (P5) inner ear spiral ganglion (SG) neurites. The response to both ECM molecules was dose-dependent. In a LN versus poly-L-lysine (PLL) assay, neurites were more often observed on PLL at low coating concentrations (5 and 10 microg/mL), while they were more often on LN at a high concentration (80 microg/mL). In a FN versus PLL assay, neurites were more often on PLL than on FN stripes at high coating concentrations (40 and 80 microg/mL). In a direct competition between LN and FN, neurites were observed on LN significantly more often than on FN at both 10 and 40 microg/mL. The data suggest a preference by SG neurites for LN at high concentrations, as well as avoidance of both LN at low and FN at high concentrations. The results also support a potential model for neurite guidance in the developing inner ear in vivo. LN, in the SG and osseus spiral lamina may promote SG dendrite growth toward the organ of Corti. Within the organ of Corti, lower concentrations of LN may slow neurite growth, with FN beneath each row of hair cells providing a stop or avoidance signal. This could allow growth cone filopodia increased time to sample their cellular targets, or direct the fibers upward toward the hair cells.

Health-related quality of life in patients with chronic respiratory failure after long-term mechanical ventilation.

STUDY OBJECTIVES: This study was aimed at assessing health-related quality of life (HRQL) in patients with chronic respiratory failure (CRF) and long-term survival following prolonged intensive care mechanical ventilation. DESIGN: Observational cohort study. SETTING: Patients with CRF who had been transferred to our specialized weaning centre due to prolonged mechanical ventilation (>14 days) and weaning failure. PATIENTS AND PARTICIPANTS: Out of 87 long-term survivors (>6 months), 73 patients (mean age: 60.3+/-13.6 years, chronic obstructive pulmonary disease (COPD, 43%), thoraco-restrictive (21%) or neuromuscular disorders (15%), various chronic diseases (22%)) returned the MOS 36-Item Short-Form Health Status Survey (SF-36) and the St. George's respiratory questionnaire (SGRQ). MEASUREMENTS AND RESULTS: The total ventilation time was 38.7+/-45.9 days. The time between discharge from ICU and HRQL assessment was 31.0+/-22.2 months. Physical health was markedly reduced compared to general population norm, but mental health was mildly impaired. HRQL was comparable to patients with stable CRF receiving non-invasive ventilation who did not need prolonged invasive MV. In addition, general HRQL was better in patients with restrictive respiratory disease compared to patients with neuromuscular diseases (P<0.05). Physiological parameters such as blood gases or lung function parameters were not correlated to any HRQL measurements. CONCLUSIONS: In patients with CRF surviving prolonged ventilation on ICU, the presence of CRF itself is the major determinant of HRQL. Here, the underlying cause of CRF is the major factor which determines the degree of HRQL impairment with patients suffering from restrictive ventilatory disorders reporting the best HRQL when compared to patients with COPD or neuromuscular diseases. Despite severe physical handicaps due to CRF mental health is only mildly compromised.