The influence of obstructive sleep apnea and continuous positive airway pressure on the nasal microbiome.

OBJECTIVE: The aim of this study was to investigate the influence of obstructive sleep apnea and continuous positive airway pressure on the nasal microbiome. PATIENTS AND METHODS: Endonasal swabs from the olfactory groove of 22 patients with moderate and severe obstructive sleep apnea (OSA) and a control group of 17 healthy controls were obtained at the Department of Otorhinolaryngology of the Friedrich-Alexander-Universität Erlangen-Nürnberg. 16S rRNA gene sequencing was performed to further evaluate the endonasal microbiome. In a second step, the longitudinal influence of continuous positive airway pressure (CPAP) therapy on the nasal microbiome was investigated (3-6 and 6-9 months). RESULTS: Analysis of the bacterial load and ß-diversity showed no significant differences between the groups, although patients with severe OSA showed increased α-diversity compared to the control group, while those with moderate OSA showed decreased α-diversity. The evaluation of longitudinal changes in the nasal microbiota during CPAP treatment showed no significant difference in α- or ß-diversity. However, the number of bacteria for which a significant difference between moderate and severe OSA was found in the linear discriminant analysis decreased during CPAP treatment. CONCLUSIONS: Long-term CPAP treatment showed an alignment of the composition of the nasal microbiome in patients with moderate and severe OSA as well as an alignment of biodiversity with that of the healthy control group. This change in the composition of the microbiome could be both part of the therapeutic effect in CPAP therapy and a promoting factor of the adverse side effects of the therapy. Further studies are needed to investigate whether the endonasal microbiome is related to CPAP compliance and whether CPAP compliance can be positively influenced in the future by therapeutic modification of the microbiome.

TIMP-1 as a biomarker in obstructive sleep apnea: screening, monitoring, risk stratification, and a step towards precision medicine.

OBJECTIVE: The diagnosis of obstructive sleep apnea (OSA) is a complex time- and resource-intensive diagnostic procedure. Since tissue inhibitors of matrix metalloproteinases (TIMP's) are involved in various pathophysiological processes and are correlated with a high cardiovascular risk, TIMP's appear to be a suitable candidate for an OSA-biomarker. PATIENTS AND METHODS: In a prospective controlled diagnostic study, TIMP-1 serum levels of 273 OSA-patients and controls were analyzed for correlation with OSA severity, BMI, age, sex, cardio-/ cerebrovascular comorbidities. Furthermore, longitudinal medium- and long-term effects of CPAP-treatment (n=15) on TIMP-1-levels were investigated. RESULTS: TIMP-1 was clearly linked to OSA as well as to disease severity (mild, moderate, severe; each p<0.001) and was not influenced by age, gender, BMI, or cardio-/cerebrovascular comorbidities. ROC curve analysis revealed an AUC of 0.91 ± 0.017 SE (p<0.001), suggesting a TIMP-1 cut-off value of 75 ng/ml (sensitivity 0.78; specificity 0.91) being especially sensitive for patients with severe OSA (sensitivity 0.89; specificity 0.91). The likelihood ratio was 8.88, while the diagnostic odds ratio was 37.14. CPAP-treatment led to a significant decrease of TIMP-1 after 6-8 months (p=0.008). CONCLUSIONS: TIMP-1 seems to fulfill the preconditions for a circulating OSA-biomarker: disease-specific with a mandatory presence in affected patients, reversible on treatment, reflects disease severity and provides a cutoff value between the healthy state and disease. In the clinical routine, TIMP 1 may help to stratify the individual OSA-associated cardiovascular risk and to monitor the treatment response to CPAP-therapy as a further step towards providing a personalized therapy.

Phantom-based prospective analysis of the accuracy of photo registration technology in electromagnetic navigation of the frontal skull base.

OBJECTIVE: This prospective study compared the accuracy of two different company-specific registration methods (Fiagon GmbH, Hennigsdorf, Germany) in the electromagnetic navigation of the frontal skull base. A newly developed photo registration technology (Fiagon tracey©) promises an increase in accuracy and user-friendliness, but there is no phantom-based prospective study comparing the new method with the classic approach of tactile surface registration. MATERIALS AND METHODS: A phantom skull was prepared with 27 markers in the sagittal, axial and coronary planes, and their reference coordinates were determined using a navigational CT (low dose, slice 0.6 mm). Subsequently, 20 runs of automatic photo registration and tactile surface registration were carried out, and the resulting marker coordinates were compared with the reference coordinates. The target registration error (TRE) of the 27 markers was assessed and compared between the two methods using a 2-factor ANOVA with repeated measures. RESULTS: The mean TRE using surface registration was 1.97 mm ± 0.57, while the mean TRE of the automatic photo registration was 1.54 mm ± 0.24 (p < 0.001). In a subgroup analysis limited to markers in anatomical regions of clinical relevance in terms of paranasal sinus surgery, the mean TRE for the photo registration procedure can even be reduced to 1.29 mm (± 0.43) compared to tactile registration (1.80 mm; ±0.50; p=0.01). CONCLUSIONS: Photo registration is a promising new technology in the field of electromagnetic navigation in paranasal sinus surgery. This prospective phantom-based study showed that the photo registration method achieves a significantly lower target registration error (1.29 mm) compared to the surface-based tactile registration procedure (1.80 mm).

Endoscopic laser diverticulotomy in Zenker's diverticulum: experiences with basal wound sealing using a collagen-fibrin patch.

OBJECTIVE: Very few reports investigated techniques of closure of the basal wound area to reduce severe complications like mediastinitis after endoscopic laser diverticulotomy. In this study, we report our experiences after routine use of a collagen-fibrin sealant patch for basal wound covering after laser diverticulotomy in consideration of postoperative complications and recurrence rates. PATIENTS AND METHODS: This retrospective study was conducted in a tertiary referral center and university hospital. Endoscopic laser diverticulotomies performed in our hospital between January 2006 and July 2018 were included. After complete transection of the laser septum of the diverticulum, we placed a collagen-fibrin patch onto the basal wound area to cover the opening to the mediastinum. Patient records were evaluated to assess the occurrence of perioperative complications, and the data were compared with those reported in the literature. RESULTS: A total of 127 endoscopic laser diverticulotomies were performed in 109 patients (71 men, 38 women) suffering from Zenker's diverticulum. Morality rate was 0%, in particular no mediastinitis was observed. Mediastinal emphysema was observed in two patients (1.6%), and temporary or persistent recurrent nerve palsy in one patient (0.8%) each. The mean follow-up period was 71.6±5.16 months. Recurrent symptomatic diverticulum was observed in 19.3% of the patients. CONCLUSIONS: These findings suggest that use of a collagen-fibrin sealant patch in endoscopic laser diverticulotomy may contribute to the safety of endoscopic controlled laser diverticulotomy without comprising the success rates.

Survival benefit for patients treated in a certified head and neck tumor center.

OBJECTIVE: Increasing effort has been put in the implementation and certification of head and neck tumor centers in order to establish standardized, quality assured health care for head and neck tumor patients. This study evaluated survival rates after treatment in a certified head and neck tumor center (CHNTC) vs. a non-certified head and neck tumor center (non-CHNTC) in Middle Franconia, Germany. PATIENTS AND METHODS: Age, sex, possible obituary, and typical relevant prognostic variables were analyzed. Diagnosis was recorded according to ICD10. Clinical and pathological TNM staging, tumor grading, localization, R-stage, and morphology were assessed (ICD-0). Patients diagnosed with oral cancer (N=1047) were divided into groups based on where they received their primary treatment; CHNTCs or non-CHNTCs. RESULTS: Patients treated at CHNTCs had significantly higher survival rates vs. those treated at non-CHNTC (p=0.023) in univariate analysis. In a Cox regression model, survival rates for patients with pN0 and pN+ stage were similar at both types of centers. Men with pN0 had significantly lower survival rates (HR=0.497, p<0.001). Age had a statistically significant influence on survival rates independently from pN stage (HR=1.031 per year, p<0.001 in both groups). CONCLUSIONS: Patients treated at CHNTC had better survival rates than those treated at non-CHNTC.

The Erlangen Questionnaire: a new 5-item screening tool for obstructive sleep apnea in a sleep clinic population - A prospective, double blinded study.

OBJECTIVE: The aim of this study was to develop and validate a simplified screening tool for identifying obstructive sleep apnea (OSA) in a sleep clinic population. PATIENTS AND METHODS: A total of 160 patients from a sleep clinic population was enrolled in the prospective, double-blinded study. OSA was defined by using diagnostic criteria of the ICSD-3 after overnight polysomnography (n=96) or polygraphy (n=64). The first 60 patients filled out a multi-item questionnaire and formed the development group. Subsequently, the five most predictive factors were selected to create the Erlangen Questionnaire (EQ). For validation of the EQ, the next 100 patients formed the validation group. RESULTS: The following factors were incorporated into the 5-item EQ: (1) ESS > 10, (2) age > 60, (3) gasping and (4) cardiovascular risk factors, (5) witnessed apneas. The EQ had sensitivities of 94.3%, 92.7% and 92.3%, specificities of 50.0%, 33.3% and 22.9%, positive predictive values of 81.5%, 62.9% and 29.6%, and negative predictive values of 78.9%, 78.9% and 89.5% with respect to mild, moderate and severe OSA. CONCLUSIONS: EQ is a compact 5-item-based, concise and easy-to-use screening tool to identify both male and female patients with OSA in a sleep clinic-population and exhibits all essential factors of internal and external validity. The results of the EQ are comparable to the best-validated and most commonly used STOP-Bang questionnaire regarding sensitivity and specificity in a sleep clinic population.

Microcystic adnexal carcinoma (MAC)-like squamous cell carcinoma as a differential diagnosis to Bell´s palsy: review of guidelines for refractory facial nerve palsy.

BACKGROUND: Bell´s palsy is the most common cause of facial paralysis worldwide and the most common disorder of the cranial nerves. It is a diagnosis of exclusion, accounting for 60-75% of all acquired peripheral facial nerve palsies. Our case shows the first case of a microcystic adnexal carcinoma-like squamous cell carcinoma as a cause of facial nerve palsy. CASE PRESENTATION: The patient, a 70-year-old Caucasian male, experienced subsequent functional impairment of the trigeminal and the glossopharyngeal nerve about 1½ years after refractory facial nerve palsy. An extensive clinical work-up and tissue biopsy of the surrounding parotid gland tissue was not able to determine the cause of the paralysis. Primary infiltration of the facial nerve with subsequent spreading to the trigeminal and glossopharyngeal nerve via neuroanastomoses was suspected. After discussing options with the patient, the main stem of the facial nerve was resected to ascertain the diagnosis of MAC-like squamous cell carcinoma, and radiochemotherapy was subsequently started. CONCLUSION: This case report shows that even rare neoplastic etiologies should be considered as a cause of refractory facial nerve palsy and that it is necessary to perform an extended diagnostic work-up to ascertain the diagnosis. This includes high-resolution MRI imaging and, as perilesional parotid biopsies might be inadequate for rare cases like ours, consideration of a direct nerve biopsy to establish the right diagnosis.

S100B in serum and saliva: a valid invasive or non-invasive biomarker in obstructive sleep apnea?

OBJECTIVE: The aim of this prospective study was to determine whether serum or saliva S100B could be established as an invasive or non-invasive biomarker of cerebrovascular stress due to chronic intermittent hypoxia in obstructive sleep apnea (OSA). PATIENTS AND METHODS: S100B levels in serum and saliva were measured by an enzyme-linked immunosorbent assay (ELISA) in 40 patients with polysomnographically confirmed OSA (n=34) or ronchopathy (n=6) and 20 control subjects (n=20). We also investigated four healthy volunteers (n=4) to determine whether the S100B levels in serum and saliva are dependent on the time of day. RESULTS: Serum S100B was significantly higher in OSA than in healthy control subjects (p=0.007), although it was not related to the severity of OSA and was independent of age, sex, and subjective daytime symptoms. Values of S100B in saliva showed a marked scatter, so there was no significant difference between the OSA group and controls (p=0.62). We did not find that S100B levels in either serum or saliva depended on the time of day (p=0.53; p=0.91). CONCLUSIONS: Serum S100B allows us to discriminate healthy subjects from patients with OSA. However, it does not live up to its promise as a valid invasive predictor of OSA, since it does not correlate with the severity of the disease. Also, S100B in saliva is not suitable for use as a non-invasive biomarker to detect hypoxia-induced cerebrovascular stress in OSA. This finding prevents an S100B saliva-based assessment of risk or possible extent of structural brain damage, ruling out the possibility of non-invasive home monitoring of compliance and therapeutic efficacy in cases of OSA on treatment.

[3D visualization and analysis of vocal fold dynamics]. / 3D-Visualisierung und Analyse von Stimmlippenschwingungen.

BACKGROUND: Visual investigation methods of the larynx mainly allow for the two-dimensional presentation of the three-dimensional structures of the vocal fold dynamics. The vertical component of the vocal fold dynamics is often neglected, yielding a loss of information. The latest studies show that the vertical dynamic components are in the range of the medio-lateral dynamics and play a significant role within the phonation process. OBJECTIVES: This work presents a method for future 3D reconstruction and visualization of endoscopically recorded vocal fold dynamics. MATERIALS AND METHODS: The setup contains a high-speed camera (HSC) and a laser projection system (LPS). The LPS projects a regular grid on the vocal fold surfaces and in combination with the HSC allows a three-dimensional reconstruction of the vocal fold surface. Hence, quantitative information on displacements and velocities can be provided. The applicability of the method is presented for one ex-vivo human larynx, one ex-vivo porcine larynx and one synthetic silicone larynx. RESULTS: The setup introduced allows the reconstruction of the entire visible vocal fold surfaces for each oscillation status. This enables a detailed analysis of the three dimensional dynamics (i. e. displacements, velocities, accelerations) of the vocal folds. CONCLUSIONS: The next goal is the miniaturization of the LPS to allow clinical in-vivo analysis in humans. We anticipate new insight on dependencies between 3D dynamic behavior and the quality of the acoustic outcome for healthy and disordered phonation.