Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

RATIONALE: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia and primary immunodeficiency disorders), but most cases remain idiopathic. OBJECTIVES: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. METHODS: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived, cells, cell cultures and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. MEASUREMENTS AND MAIN RESULTS: We identified bi-allelic pathogenic variants in WFDC2 in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and thus secretion of mature WFDC2. CONCLUSIONS: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Perception of Specific Musical Attributes in Dependence of the Insertion Depth of Cochlear Implant Electrodes Using the Montreal Battery of Evaluation of Amusia.

HYPOTHESIS: The insertion angle of the electrode array has an influence on the perception of different musical features. BACKGROUND: A deeper insertion of the electrodes is associated with a greater coverage of the cochlea with possible stimulus locations. This could lead to an improved or extended perception of pitches and pitch changes as well as to a better perception of contours in musical pieces. METHODS: A Montreal Battery of Evaluation of Amusia test battery was conducted with a collective of 19 cochlear implant (CI) users and 9 normal-hearing subjects. For the CI users, the insertion angles of the intracochlear electrode arrays were calculated using Otoplan software. RESULTS: Compared with normal-hearing users, CI users performed worse in the detection of melodic features of music. CI users performed better with temporal features than with melodic features. An influence of the insertion depth of the electrodes on the results of the Montreal Battery of Evaluation of Amusia could be proven neither for Cochlear nor for MED-EL CI users. CONCLUSION: Deeper insertion of electrode arrays may only better approximate the spatial-frequency map. Alone, it does not have an effect on better detection and identification of pitch and tonality and, consequently, better perception of musical attributes. Anatomy-based calculation of electrode locations and matching to characteristic frequencies will be sought in subsequent studies.

[Fundamentals and practice of the application of nasal packing in sinonasal surgery]. / Grundlagen und Praxis der Anwendung von Nasentamponaden in der endonasalen Chirurgie.

BACKGROUND AND OBJECTIVES: This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice. MATERIALS AND METHODS: Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature. RESULTS AND CONCLUSIONS: Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

Measurement of Ocular Vestibular Evoked Myogenic Potentials: Nasion Reference Montage as an Alternative to the Clinical Standard Montage.

OBJECTIVE: To compare two novel electrode montages for ocular, vestibular evoked myogenic potential using single-nasion reference electrodes with the clinical standard montage. STUDY DESIGN: Randomized crossover experiment. SETTING: Tertiary referral center. PARTICIPANTS: Sixty healthy participants. INTERVENTION: Normal hearing and vestibular function were confirmed with an extensive test-battery. All ocular, vestibular evoked myogenic potential settings were measured with air-conducted tone bursts at 100-dB normal hearing level and a frequency of 500 Hz. Three electrode montages were measured in randomized order: the clinical standard montage ("S"), the nasion reference montage ("N"), and the nasion reference montage with a more lateral active electrode ("L"). Upgaze was standardized to 35 degrees. MAIN OUTCOME MEASURES: Detection rate, latency of N1 and P1, peak-to-peak amplitude of N1 and P1, signal-to-noise ratio (SNR), asymmetry ratio (AR), concordance of expert assessment, and reliability. RESULTS: All electrode montages showed detection rates greater than 90%. Latencies for "L" were shorter than for "S" and "N." Amplitudes and SNR for "S" and "N" were higher than for "L," whereas the values for "S" and "N" did not differ significantly. For AR, no significant differences between the montages were assessed. Concordance of experts ranged from 78% for "L" and 89.8% for "N." All montages provided excellent day-to-day reliability (intraclass correlation coefficient ≥0.9) for amplitudes and SNR. CONCLUSIONS: Montage N could be a useful alternative to the clinical standard montage: although results are roughly equivalent, montage N requires one less electrode to do so.

Effects of squamous cell carcinoma and smoking status on oropharyngeal and laryngeal microbial communities.

BACKGROUND: Still, little is known about microbial dysbiosis in oropharyngeal and laryngeal tissue as risk factor for development of local squamous cell carcinoma. The site-specific microbiota at these regions in healthy and cancer tissue and their modulation by environmental factors need to be defined. METHODS: The local microbiota of cancer tissue and healthy controls was profiled by 16S rRNA gene amplicon sequencing and statistical analysis using 111 oropharyngeal and 72 laryngeal intraoperative swabs. RESULTS: Oropharynx and larynx harbor distinct microbial communities. Clear effects of both smoking and cancer were seen in the oropharynx whereas effects in the larynx were minor. CONCLUSION: The distinct microbial communities at larynx and oropharynx partially explain why the effects of cancer and smoking were distinct at those sites. Thus, the use of microbiota supposed to mirror community changes in another target location should be avoided and more studies on the actual cancerous environment are necessary.

Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis.

Background: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmark symptom of PCD. Data on genotype-phenotype correlations in the upper airways are scarce. Materials and methods: We investigated the prevalence, radiologic severity, and impact on health-related quality of life (HrQoL) of CRS in 58 individuals with genetically confirmed PCD. Subgroup analysis was performed according to the predicted ultrastructural phenotype based on genetic findings. Results: Among 58 individuals harboring pathogenic variants in 22 distinct genes associated with PCD, all were diagnosed with CRS, and 47% underwent sinus surgery. A total of 36 individuals answered a German-adapted version of the 20-item Sinonasal Outcome Test (SNOT-20-GAV) with a mean score of 35.8 ± 17, indicating a remarkably reduced HrQoL. Paranasal sinus imaging of 36 individuals showed moderate-to-severe opacification with an elevated Lund-Mackay Score (LMS) of 10.2 ± 4.4. Bilateral agenesis of frontal sinus (19%) and sphenoid sinus (9.5%) was a frequent finding in individuals aged 16 years or older. Subgroup analysis for predicted ultrastructural phenotypes did not identify differences in HrQoL, extent of sinus opacification, or frequency of aplastic paranasal sinuses. Conclusion: PCD is strongly associated with CRS. The high burden of disease is indicated by decreased HrQoL. Therefore, the upper airways of PCD individuals should be evaluated and managed by ear-nose-throat (ENT) specialists. Genetically determined PCD groups with predicted abnormal versus (near) normal ultrastructure did not differ in disease severity. Further studies are needed to gain evidence-based knowledge of the phenotype and management of upper airway manifestations in PCD. In addition, individuals with agenesis of the frontal and sphenoid paranasal sinuses and chronic respiratory symptoms should be considered for a diagnostic evaluation of PCD.

[Functional disorders of the nose - definition, diagnostics and treatment options]. / Funktionelle Formstörungen der Nase ­ Definition, Diagnostik und Therapieoptionen.

The surgical spectrum of functional rhinosurgery includes nasal septum surgery, septorhinoplasty and nasal concha surgery. Based on the German guideline "Disorders of the inner and/or external nose (with functional and/or aesthetic impairment)" published in April 2022, which was prepared on behalf of the German Society of Otorhinolaryngology, Head and Neck Surgery, we discuss the indications, diagnostic approaches, the planning of the surgery and postoperative care. The most common findings of the external nose with a functional impairment include crooked nose, saddle nose, and tension nose. Combined pathologies occur. Well-documented in-depth consultation is essential for rhinosurgical procedures. In the case of revision surgery, the possible necessity of autologous ear or rib cartilage should be considered. Despite correct surgical performance, no "guarantee" can be given for the surgical (long-term) result in rhinosurgery.

[Treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with monoclonal antibodies (biologics): S2k guideline of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German College of General Practitioners and Family Physicians (DEGAM)]. / Therapie der chronischen Rhinosinusitis mit Polyposis nasi (CRScNP) mit monoklonalen Antikörpern (Biologika): S2k-Leitlinie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) und der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM).

Monoclonal antibodies (so-called biologics) can be prescribed for chronic rhinosinusitis with nasal polyps (CRSwNP) within the scope of their market authorization. However, their prescription is limited to severe CRSwNP without disease control, whereby certain requirements must be met. Dupilumab, omalizumab, and mepolizumab have currently gained market authorization, with adequate evidence for their efficacy and safety available in the literature. It can be assumed that other biologics will be approved for this indication in the future. The severity of disease and the efficacy of treatment should be assessed objectively and subjectively before treatment initiation and after an appropriate duration, respectively. The documentation sheet proposed in this guideline chapter can be used for the assessments. In the presence of relative contraindications, a treatment should only be initiated after differentiated consideration by an experienced physician in the sense of a case-by-case decision. In summary, this guideline chapter aims to contribute to high-quality care of adult patients with these therapies in view of the increasing evidence for treatment with these substances and the increasing number of market authorizations of different biologics.

Phytomedicine ELOM-080 in Acute Viral Rhinosinusitis: A Randomized, Placebo-Controlled, Blinded Clinical Trial.

BACKGROUND: ELOM-080 is a phytomedicine approved for the treatment of acute and chronic inflammatory diseases of the respiratory tract, sinusitis, and bronchitis in particular. This prospective, randomized, placebo-controlled, double-blind clinical trial was conducted to assess efficacy and safety of ELOM-080 in the treatment of acute viral rhinosinusitis (AVRS). METHODS: Patients with AVRS received oral treatment (4 × 1 capsule per day) with either ELOM-080 or matching placebo. Primary endpoints were the change in major symptom score (MSS) after 7 and 14 days of treatment assessed by the investigator (MSSINV ). Secondary endpoints were changes in MSS assessed by the patients (MSSPAT ), olfactory function (12-item Sniffin' Sticks), 20-Item Sino-Nasal Outcome Test (SNOT-20 GAV; German adapted version), influence of treatment on viral load, and safety. RESULTS: Four hundred and sixty-three patients were randomized. At day 4, subjective burden of disease (MSS) was significantly ameliorated compared to placebo (p = 0.012). During the first treatment week MSS scores improved about 1 day earlier, and 3 days earlier in the second week. Effect with ELOM-080 on mean MSSINV was statistically significantly superior to placebo at visit 3 (p = 0.016) and visit 4 (p = 0.014). In chemosensory testing identification scores improved comparably in both treatments. The improvement of the SNOT-20 GAV was more pronounced in ELOM-080 patients. Treatment with ELOM-080 indicated a potential for decreasing viral load. Both treatments were well tolerated. CONCLUSION: ELOM-080 improves the burden of AVRS significantly in comparison to placebo, remission of symptoms occurred 3 days earlier. The results confirm the efficacy and safety of ELOM-080 for treatment of AVRS. LEVEL OF EVIDENCE: 1 Laryngoscope, 133:1576-1583, 2023.

Population Based Average Parotid Gland Volume and Prevalence of Incidental Tumors in T1-MRI.

Representative epidemiologic data on the average volume of the parotid gland in a large population-based MRI survey is non-existent. Within the Study of Health in Pomerania (SHIP), we examined the parotid gland in 1725 non-contrast MRI-scans in T1 weighted sequence of axial layers. Thus, a reliable standard operating procedure (Intraclass Correlation Coefficient > 0.8) could be established. In this study, we found an average, single sided parotid gland volume of 27.82 cm3 (95% confidence interval (CI) 27.15 to 28.50) in male and 21.60 cm3 (95% CI 21.16 to 22.05) in female subjects. We observed positive associations for age, body mass index (BMI), as well as male sex with parotid gland size in a multivariate model. The prevalence of incidental tumors within the parotid gland regardless of dignity was 3.94% in the Northeast German population, slightly higher than assumed. Further epidemiologic investigations regarding primary salivary gland diseases are necessary.

Framework and baseline examination of the German National Cohort (NAKO).

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

Detecting myositis as a cause of unexplained dysphagia: Proposal for a diagnostic algorithm.

BACKGROUND AND PURPOSE: Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia. METHODS: Over a period of 4 years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted. RESULTS: Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients. CONCLUSIONS: Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures.

Awake Rhinology Surgery in Response to the COVID-19 Pandemic in Europe.

BACKGROUND: European health-care systems are faced with a backlog of surgical procedures following the suspension of routine surgery during the COVID-19 crisis. Routine rhinology surgery under general anaesthetic (GA) is now faced with significant challenges which include limited theatre capacity, the negative ramifications of surgical prioritization, reduced patient throughput in secondary care, and additional personal protective equipment requirements. Delayed surgery in rhinology, particularly with regards to chronic rhinosinusitis, has previously been shown to have poorer surgical outcomes, a detrimental effect on quality of life and long-term negative health socio-economic effects. Awake rhinology surgery under local anaesthetic (LA) provides an ideal alternative to GA. It provides a means of operating on patients in a setting alternative to currently oversubscribed main theatres, by utilizing satellite facilities, while ensuring identical surgical outcomes for patients who may otherwise have been forced to wait a long time for their procedure. It also confers additional benefits in terms of shorter recovery time and hospital stay for patients. OBJECTIVES: We have developed a set of recommendations that are intended to help support clinicians and managers to better adopt LA rhinology protocols and minimize the risk to the patient and health-care professionals involved. METHODOLOGY: International roundtable forums were conducted and supplemented by individual interviews. The international board consisted of 12 rhinologists experienced in awake rhinology surgery. Feedback was analysed and shared to develop a consensus of best practice. RECOMMENDATIONS: Local and national guidelines need to be adhered to with specific focus on patient and clinician safety. When performing awake rhinology procedures in the COVID-19 recovery process, consider implementing specific safety measures and workflow practices to safeguard patients and staff and minimize the risk of infection. CONCLUSION: Awake surgery potentially provides quicker access to routine rhinology surgery in the post-COVID-19 recovery phase, ensuring patients are treated in a timely matter, thereby avoiding higher downstream costs, and improving outcomes.

Cross-cultural adaptation and validation of the 22-item sinonasal outcome test (SNOT-22) in German-speaking patients: a prospective, multicenter cohort study.

PURPOSE: Chronic rhinosinusitis (CRS) is a common condition associated with a significant reduction of the health-related quality of life. One of the most widely used assessment tools in CRS is the disease-specific, health-related questionnaire SNOT-22. The aim of this study was to translate and validate the SNOT-22 into the German language. METHODS: The questionnaire was translated using the forward-backward translation technique. After the translation its reliability, validity, and sensitivity were evaluated. For this purpose, the questionnaire was completed by patients diagnosed with CRS before, 3 months and 1 year after endoscopic sinus surgery and by healthy individuals as controls at three university hospitals in Germany. The individual scores of the questionnaire before surgery was correlated with the Lund-Mackay score as well as a global disease-specific question. RESULTS: A total of 139 CRS patients and 31 healthy individuals participated in the study. Internal consistency at all timepoints was very good, with Cronbach's alpha scores of 0.897, 0.941, and 0.945. The questionnaire was able to discriminate between CRS patients and control subjects (p < 0.0001) and scores improved significantly 3 month and 1 year after sinus surgery (p < 0.0001), indicating a good test-retest reliability, validity, and responsiveness. A significant correlation to the single global disease-specific question could be found (p < 0.0001), but no correlation with the Lund-Mackay score. CONCLUSION: The German Version of the SNOT-22 is a reliable, valid, and sensitive instrument for measuring health-related quality of life in patients with CRS. It can be recommended for clinical practice and outcome research for German-speaking patients.

Improvement of patient stratification in human papilloma virus-associated oropharyngeal squamous cell carcinoma by defining a multivariable risk score.

BACKGROUND: Precise risk stratification models are necessary to determine patient selection for deintensifying treatment trials in human papilloma virus (HPV)-associated oropharyngeal squamous cell cancer (HPV+ OPSCC). METHODS: We examined 526 cases with OPSCC treated at our department between 2002 and 2017. Every patient was classified after the 7th and 8th edition UICC staging manual. For HPV+ OPSCC, we calculated a simple risk score with four risk groups based on multivariable Cox regression analysis of clinical and lifestyle parameters (UICC 8th edition stage, tobacco/alcohol abuse, age, gender). RESULTS: Two hundred and thirty-nine patients with OPSCC (45.4%) showed a positive histological HPV status. In comparison to UICC 8th edition stages, our proposed risk model showed a tendency for better stratification between risk strata I/III, I/IV, and II/IV (each p < 0.002) and I/II, II/III, and III/IV (each p < 0.09). CONCLUSION: Age, gender, tobacco, and alcohol abuse should be added to the current UICC staging system in order to improve risk stratification in HPV+ OPSCC.

Follow-up of a national web-based survey on the SARS-CoV-2 infectious state of otorhinolaryngologists in Germany.

PURPOSE: The SARS-CoV­2 pandemic has affected the health and practice of otorhinolaryngologists (ORLs) for over 1 year. Follow-up data of a national survey with German ORLs were evaluated regarding differences between the two waves of the pandemic. METHODS: As in the initial survey, German ORLs were addressed via e­mail through the German Society of ORL, Head and Neck Surgery and the German ENT Association. All ORLs afflicted with SARS-CoV­2 were invited to participate in a web-based survey. General data on infections and concomitant parameters were evaluated. RESULTS: Since the start of the pandemic, 129 ORLs reported testing positive for SARS-CoV­2 in Germany. The ORLs infected during the first wave had a relative risk (RR) of 4.07 (95% CI: 3.20; 5.19) of contracting SARS-CoV­2. During the second wave, the RR decreased to 0.35 (95% CI: 0.28; 0.45). The availability of personal protective equipment (PPE) increased from the first to the second wave along with an increased perception of protection in the professional environment. The source of infection shifted from infections via medical staff during the first wave to patients and household exposure during the second wave. Regular medical practice was resumed by clinicians and general practitioners in the second wave. Nevertheless, a proportionally lower infection rate was observed compared with the German population as a whole. CONCLUSION: The data reflect a unique long-term survey of ORLs during the pandemic. Differences in the source of infection were seen between the first and second wave, confirming the need for appropriate PPE for medical professionals working in high-risk environments. Further strategies to reduce the risk of infection include consistent testing for SARS-CoV­2 in healthcare professionals, patients, and the general public as well as vaccination of high-risk medical groups.

Long-Term Follow-Up on Systemic Bevacizumab Treatment in Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a primarily benign disease affecting the entire respiratory tract. Treatment is challenging and usually involves surgical interventions and adjuvant medications. Previously, promising results on systemic administration of bevacizumab have been reported. However, experience on long-term systemic use in patients with RRP is not yet available. Here, we present our long-term follow-up on RRP patients undergoing systemic bevacizumab treatment. STUDY DESIGN: Case series. METHODS: To describe experience on long-term systemic bevacizumab administration, we performed the underlying investigation. Clinical, radiological, and bronchoscopy data were collected. RESULTS: To date, a total of n = 5 patients has been treated with systemic bevacizumab at Muenster University Hospital. With a median follow-up since first systemic bevacizumab administration of 95.5 months long-term follow-up is illustrated. Following bevacizumab treatment partial remission or very good partial remission were achieved in all patients. After papilloma recurrence/progression due to bevacizumab discontinuation, further response was documented in all patients in whom bevacizumab was started again. In one patient, bevacizumab was discontinued due to loss of efficacy. Lung cancer developed in one patient with pulmonary papillomatosis prior to bevacizumab administration whereas three patients suffered from malignant transformation during bevacizumab treatment. Systemic bevacizumab led to long-term reduction in surgical interventions in all patients. Except from mild proteinuria and hypertension in two patients therapy was well tolerated. CONCLUSIONS: Systemic bevacizumab represents a promising long-term treatment option for aggressive forms of papillomatosis. Rate of malignant transformation under bevacizumab treatment, optimal treatment schedule, and influence on survival should be further evaluated in clinical trials. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1926-E1933, 2021.

Results of a national web-based survey on the SARS-CoV-2 infectious state of otorhinolaryngologists in Germany.

PURPOSE: SARS-CoV-2 is detected on the mucosa of the upper airways to a high degree. In the course of the COVID-19 pandemic, otorhinolaryngologists (ORL) are assumed to be at high risk due to close contact with the mucosa of the upper airways. No data are yet available providing evidence that ORLs have an increased risk of infection. METHODS: German ORLs were invited via e-mail through the German Society of ORL, Head and Neck Surgery and the German ENT Association to participate in a web-based survey about infection with SARS-CoV-2 and development of COVID-19. Data of infections and concomitant parameters in German ORLs were collected and compared to the total number of infections in Germany. RESULTS: Out of 6383 German ORLs, 970 (15%) participated. 54 ORLs reported testing positive for SARS-CoV-2. Compared to the total population of Germany, ORLs have a relative risk of 3.67 (95% CI 2.82; 4.79) of contracting SARS-CoV-2. Domestic quarantine was conducted in 96.3% of cases. Two individuals were admitted to hospital without intensive care. No casualties were reported. In 31 cases, the source of infection was not identifiable whereas 23 had a clear medical aetiology: infected patients: n = 5, 9.26%; medical staff: n = 13, 14.1%. 9.26% (n = 5) of the identified cases were related to contact to infected family members (n = 3), closer neighbourhood (n = 1) or general public (n = 1). There was no identified increased risk of infection due to performing surgery. CONCLUSION: German ORLs have an almost 3.7-fold risk of contracting SARS-CoV-2 compared to the population baseline level. Appropriate protection appears to be necessary for this occupational group.