Publications by authors named "Heidi Olze"

95 Publications

Challenges of Cochlear Implantation in Intralabyrinthine Schwannoma Patients: Surgical Procedures and Auditory Outcome.

J Clin Med 2021 Aug 30;10(17). Epub 2021 Aug 30.

Department of Otorhinolaryngology, Head and Neck Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Intralabyrinthine schwannoma (ILS) is a rare benign tumor of the inner ear potentially causing unilateral sensorineural hearing loss and vertigo. This study evaluated the outcome of one surgical session comprising microsurgical ILS resection and cochlear implantation in terms of surgical feasibility, complications, and auditory outcome. Ten clinically and histologically confirmed ILS patients included in this study (three women and seven men; mean age 56.4 ± 8.6) underwent surgery between July 2015 and February 2020. Eight patients had intracochlear tumor location; the remaining two had vestibulocochlear and intravestibular ILS. One of the three following methods was used for tumor removal: an extended cochleostomy, subtotal cochleoectomy, or a translabyrinthine approach. Although negligible improvement was observed in two of the patients, two patients were lost to follow-up, and one opted out from using CI, the speech perception of the five remaining ILS patients improved as per the Freiburg Monosyllable Test (FMT) from 0% before surgery to 45- 50% after the implantation. Our study supports the presented surgical approach's feasibility and safety, enabling tumor removal and hearing restoration shortly after surgery.
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http://dx.doi.org/10.3390/jcm10173899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432191PMC
August 2021

Improvement of Working Memory and Processing Speed in Patients over 70 with Bilateral Hearing Impairment Following Unilateral Cochlear Implantation.

J Clin Med 2021 Jul 31;10(15). Epub 2021 Jul 31.

Department of Otorhinolaryngology, Head and Neck Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Several studies demonstrated the association of hearing disorders with neurocognitive deficits and dementia disorders, but little is known about the effects of auditory rehabilitation on the cognitive performance of the elderly. Therefore, the research question of the present study was whether cochlear implantation, performed in 21 patients over 70 with bilateral severe hearing impairment, could influence their cognitive skills. The measuring points were before implantation and 12 months after the first cochlear implant (CI) fitting. Evaluation of the working memory (WMI) and processing speed (PSI) was performed using the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV). The audiological assessment included speech perception (SP) in quiet (Freiburg monosyllabic test; FMT), noise (Oldenburg sentence test; OLSA), and self-assessment inventory (Oldenburg Inventory; OI). Twelve months after the first CI fitting, not only the auditory parameters (SP and OI), but also the WMI and PSI, improved significantly ( < 0.05) in the cohort. The presented results imply that cochlear implantation of bilaterally hearing-impaired patients over 70 positively influences their cognitive skills.
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http://dx.doi.org/10.3390/jcm10153421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347702PMC
July 2021

Classifying and Predicting Surgical Complications After Laryngectomy: A Novel Approach to Diagnosing and Treating Patients.

Ear Nose Throat J 2021 Jul 30:1455613211029749. Epub 2021 Jul 30.

Department of Otolaryngology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Objectives: The total laryngectomy is one of the most standardized major surgical procedures in otolaryngology. Several studies have proposed the Clavien-Dindo classification (CDC) as a solution to classifying postoperative complications into 5 grades from less severe to severe. Yet more data on classifying larger patient populations undergoing major otolaryngologic surgery according to the CDC are needed. Predicting postoperative complications in clinical practice is often subject to generalized clinical scoring systems with uncertain predictive abilities for otolaryngologic surgery. Machine learning offers methods to predict postoperative complications based on data obtained prior to surgery.

Methods: We included all patients (N = 148) who underwent a total laryngectomy after diagnosis of squamous cell carcinoma at our institution. A univariate and multivariate logistic regression analysis of multiple complex risk factors was performed, and patients were grouped into severe postoperative complications (CDC ≥ 4) and less severe complications. Four different commonly used machine learning algorithms were trained on the dataset. The best model was selected to predict postoperative complications on the complete dataset.

Results: Univariate analysis showed that the most significant predictors for postoperative complications were the Charlson Comorbidity Index (CCI) and whether reconstruction was performed intraoperatively. A multivariate analysis showed that the CCI and reconstruction remained significant. The commonly used AdaBoost algorithm achieved the highest area under the curve with 0.77 with high positive and negative predictive values in subsequent analysis.

Conclusions: This study shows that postoperative complications can be classified according to the CDC with the CCI being a useful screening tool to predict patients at risk for postoperative complications. We provide evidence that could help identify single patients at risk for complications and customize treatment accordingly which could finally lead to a custom approach for every patient. We also suggest that there is no increase in complications with patients of higher age.
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http://dx.doi.org/10.1177/01455613211029749DOI Listing
July 2021

Ultrasound Shear Wave Elastography of the Tongue during Selective Hypoglossal Nerve Stimulation in Patients with Obstructive Sleep Apnea Syndrome.

Ultrasound Med Biol 2021 Oct 21;47(10):2869-2879. Epub 2021 Jul 21.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Radiology, Berlin Institute of Health, Berlin, Germany.

Currently, there is no established technique to directly measure extrinsic tongue muscle activation during selective hypoglossal stimulation therapy (sHNS) in patients with obstructive sleep apnea syndrome (OSAS) in a simple, non-invasive clinical setting. Ultrasound shear-wave elastography (US-SWE) enables quantitative measurement of tissue stiffness. We investigated whether US-SWE is able to detect changes in muscle stiffness of the tongue during sHNS. Patients with OSAS treated with sHNS were prospectively enrolled. A standardized US-SWE protocol was used to selectively measure tissue stiffness of the geniohyoid muscle (GH) and genioglossus (GG) muscles on the side of stimulator implantation (sGH, sGG) and on the contralateral side (nGH, nGG) without and with sHNS. Eighteen patients were included (median age = 62 years, interquartile range: 56-65, 83.3% male). Median shear-wave velocity (SWV) increased during contraction with each patient's clinically prescribed therapeutic regimen in the sGH (+19%, p = 0.020) and sGG (+81%, p < 0.001) and decreased during contraction in the nGH (-8%, p = 0.107) and nGG (-8%, p = 0.396). Differences in SWV during contraction were significant only on the side of stimulation (sGG +81%, sGH +19%). SWE measurements had excellent reliability as reflected by a Cronbach α value ≥0.9 for all target muscles pre- and post-contraction and an item-total correlation ≥0.5. US-SWE allows reliable measurement of SWV as an indicator of muscle stiffness of extrinsic tongue muscles. This non-invasive method provides new possibilities to distinguish and characterize responders from non-responders in hypoglossal stimulation therapy. Compared with the regular visual assessment of tongue movement, US-SWE of individual muscle groups provides a new non-invasive imaging tool in patients with OSAS.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.06.009DOI Listing
October 2021

Untersuchung genetischer Einflüsse auf Riechstörungen bei Patienten mit hereditärem Angioödem Typ 1 und 2.

J Dtsch Dermatol Ges 2021 Jul;19(7):1060-1063

Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland.

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http://dx.doi.org/10.1111/ddg.14417_gDOI Listing
July 2021

The Diagnostic Yield of Excisional Biopsy in Cervical Lymphadenopathy: A Retrospective Analysis of 158 Biopsies in Adults.

Ear Nose Throat J 2021 Jun 7:1455613211023009. Epub 2021 Jun 7.

Department of Otorhinolaryngology, 14903Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Objectives: Cervical lymph nodes are the most common site of peripheral lymphadenopathy. The underlying etiologies are usually benign and self-limiting but may include malignancies or other severe life-threatening diseases. The aim of the current study was to investigate the various underlying pathologies of cervical lymphadenopathy as assessed by the diagnostic yield of excisional lymph node biopsies of the neck in a tertiary adult practice. The evaluation was performed in light of previous literature and regional epidemiological patterns.

Methods: Retrospective analysis of hospital charts of 158 adult patients who underwent an excisional biopsy for suspected cervical lymphadenopathy at a tertiary referral head and neck service between January 2017 and December 2019.

Results: The most common underlying pathology was unspecific and/or reactive lymphadenitis in 44.5% of specimens, followed by malignant disease in 38.6% of cases. An age above 40 years was significantly correlated with an increased likelihood of malignant disease. Lower jugular and posterior triangle lymph nodes showed higher malignancy rates than other groups (100% and 66.7%, respectively). The overall surgical complication rate was 2.5%.

Conclusions: The results of the current study serve as an indicator of the variety of etiologies causing cervical lymphadenopathy. In particular, given the increasing incidence of malignant diseases in recent decades, the findings should alert physicians to the importance of lymph node biopsy for excluding malignancy in persistent cervical lymphadenopathy especially in older adults. The findings emphasize the value of excisional lymph node biopsy of the neck as a useful diagnostic tool in adult patients with peripheral lymphadenopathy.
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http://dx.doi.org/10.1177/01455613211023009DOI Listing
June 2021

White Matter Lesions as Possible Predictors of Audiological Performance in Adults after Cochlear Implantation.

Brain Sci 2021 May 8;11(5). Epub 2021 May 8.

Department of Otorhinolaryngology, Head and Neck Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

The presented prospective study investigated whether structural brain damage, measured with the Fazekas score, could predict hearing rehabilitation outcomes with cochlear implantation (CI). With a follow-up period of 24 months, this study included 49 bilaterally, postlingually hearing impaired CI candidates for unilateral CI (67.3 ± 8.7 years; 20 men, 29 women) older than 50 at the time of implantation. The differences in the predictive value between two age groups, 50-70 year-olds (mid-age; = 26) and over 70-year-olds (elderly; = 23), were analyzed. The patients were evaluated using speech perception (SP) measured in quiet (Freiburg monosyllabic test; FMT) and noise (Oldenburg sentence test; OLSA). The subjective hearing ability was assessed using Oldenburg inventory (OI). The Fazekas PVWM score predicted postoperative speech perception two years after CI in the mid-age population. The periventricular white matter lesions (PVWM) could explain 27.4% of the speech perception (FMT) variance. Our findings support the hypothesis about the influence of pre-existing WMLs on CI outcome. We recommend the evaluation of Fazekas score as a predictive factor for post-implantation hearing ability.
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http://dx.doi.org/10.3390/brainsci11050600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150980PMC
May 2021

Analysis of genetic impact on smell impairment in patients with hereditary angioedema type 1 and 2.

J Dtsch Dermatol Ges 2021 Jul 20;19(7):1060-1062. Epub 2021 May 20.

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1111/ddg.14417DOI Listing
July 2021

Duration of deafness impacts auditory performance after cochlear implantation: A meta-analysis.

Laryngoscope Investig Otolaryngol 2021 Apr 4;6(2):291-301. Epub 2021 Feb 4.

Department of Otorhinolaryngology, Head and Neck Surgery Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Germany.

Objective: Hearing loss is a highly disabling condition. Cochlear implantation is an established remedy if conventional hearing aids have failed to alleviate the level of disability. Unfortunately, cochlear implant (CI) performance varies dramatically. This study aims to examine the effects of duration of deafness (DoD) prior to cochlear implantation and the postoperative duration of implant experience with resulting hearing performance in postlingually deaf patients.

Methods: A systematic literature review and two meta-analyses were conducted using the search terms AND . Included studies evaluate the correlation between the DoD and auditory performance after cochlear implantation using monosyllabic and sentence tests. Correlation coefficients were determined using Pearson's correlation and Spearman rho.

Results: A total of 36 studies were identified and included data on cochlear implantations following postlingual deafness and postoperative speech testing of hearing outcomes for 1802 patients. The mean age ranged from 44 to 68 years with a DoD of 0.1 to 77 years. Cochlear implant use varied from 3 months to 14 years of age. Speech perception, which was assessed by sentence and monosyllabic word perception, was negatively correlated with DoD. Subgroup analyses revealed worse outcomes for longer DoD and shorter postoperative follow-up.

Conclusion: DoD is one of the most important factors to predict speech perception after cochlear implantation in postlingually deaf patients. The meta-analyses revealed a negative correlation between length of auditory deprivation and postoperative sentence and monosyllabic speech perception. Longer DoD seems to lead to worse CI performance, whereas more experience with CI mitigates the effect.
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http://dx.doi.org/10.1002/lio2.528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035957PMC
April 2021

Carcinoma of Unknown Primary and the 8th Edition TNM Classification for Head and Neck Cancer.

Laryngoscope 2021 09 18;131(9):E2534-E2542. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.

Objective: In the 8th Edition TNM Classification for Head and Neck Cancer, the classification for carcinoma of unknown primary (CUP) changed in addition to oropharyngeal carcinomas. The current classification considers extranodal extension (ENE), determination of p16 (surrogate marker for human papillomavirus), and detection of Epstein-Barr virus (EBV). The aim of this study was to investigate the influence of the new classification on the prognosis of p16-positive and p16-negative CUP and the impact of EBV proof.

Methods: Clinical and pathological data from patients with CUP of the head and neck between 2009 and 2018 were evaluated. The 7th (UICC7) and 8th (UICC8) edition of the Union for International Cancer Control staging system were applied and compared.

Results: There were 97 patients treated, 26.8% women and 73.2% men. The average age at initial diagnosis was 64.6 years. Of which, 58.8% had a documented history of smoking, 37.1% were positive for p16, 4.1% were positive for EBV, and 66% had ENE. Most of the patients were at stage III/IVa (78.4% according to UICC7). According to UICC8, p16+ patients were mainly at stage I (86.1%), and p16- at stage IVb (56.1%). P16 status (P = .002), ENE (P = .001), nodal category (TNM7, P < .001), UICC stage (TNM7, P < .001) and UICC stage (TNM8, P < .001) had a significant impact on survival in the univariate analysis. The 8th TNM classification resulted in a downstaging of p16-positive CUP syndromes and an upstaging of p16-negative syndromes.

Conclusion: The 8th TNM classification shows the lower UICC stage in p16-positive CUP syndromes. The prognostic significance for survival has improved from the 7th to the 8th TNM classification. LEVEL OF EVIDENCE USING THE 2011 OCEBM: Level 3. Laryngoscope, 131:E2534-E2542, 2021.
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http://dx.doi.org/10.1002/lary.29499DOI Listing
September 2021

Impact of Smoking on the Survival of Patients With High-risk HPV-positive HNSCC: A Meta-analysis.

In Vivo 2021 Mar-Apr;35(2):1017-1026

Department of Otorhinolaryngology, Head and Neck Surgery (CVK and CCM), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;

Background/aim: High risk Human papillomavirus (hr-HPV) and smoking are independant risk factors for head and neck squamous cell carcinomas (HNSCC). While hr-HPV HNSCC has a better prognosis than smoking-associated HNSCC no systematic data are yet available about the combined risk.

Patients And Methods: We performed a meta-analysis to assess the overall survival of HNSCC patients relative to the hr-HPV and smoking status. A literature review up to November 2019 was conducted in PubMed and Cochrane Library using the search terms 'HPV, Smoking and HNSCC'.

Results: Nine out of 748 articles were included, 1,436 out of 2,080 patients were hr-HPV The prevalence of hr-HPV smokers was 36%. The meta-analysis showed a significantly better 5-year overall survival for HPV non-smokers compared to smokers with risk ratio of 1.94 (95% confidence intervaI=1.46-2.58).

Conclusion: Smoking is a negative prognostic factor for overall survival in patients with hr-HPV HNSCC and should thus be an important part of staging and treatment.
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http://dx.doi.org/10.21873/invivo.12345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045080PMC
June 2021

Bilateral Hearing Loss Due to Metastatic Gastric Signet Cell Adenocarcinoma Involving the Internal Auditory Canal and Cerebellopontine Angle.

J Int Adv Otol 2021 Jan;17(1):87-90

Department of Otorhinolaryngology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Intracranial metastases of stomach cancers are very rare and are associated with a poor prognosis. Of those, metastases of gastric cancers in the internal auditory canal and cerebellopontine angle represent an extremely rare subgroup. Such metastatic lesions may be indistinguishable from vestibular schwannomas in imaging studies and clinical presentation. In this report, we describe a case of gastric signet cell adenocarcinoma metastasizing to the internal auditory canal and cerebellopontine angle bilaterally and causing bilateral hearing loss, including a unilateral sudden deafness. Due to the co-detection of multiple other intracranial masses in the magnetic resonance imaging scan, the suspected diagnosis of leptomeningeal metastatic disease was clear, and the patient was referred to palliative whole brain radiotherapy. The case further highlights the importance of prompt diagnosis and treatment of metastatic cerebellopontine angle lesions to prevent permanent neurological sequelae. Metastatic tumors should therefore be considered in the differential diagnosis of cerebellopontine angle lesions, especially in patients with a known history of malignant disease.
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http://dx.doi.org/10.5152/iao.2020.8415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901424PMC
January 2021

Methods for Testing the Subjective Visual Vertical during the Chronic Phase of Menière's Disease.

Diagnostics (Basel) 2021 Feb 5;11(2). Epub 2021 Feb 5.

Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität, Berlin Humboldt Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte, Chariteplatz 1, 10117 Berlin, Germany.

The subjective visual vertical (SVV) evaluates the function of the utricle, which, in patients with Menière's disease (MD), can be affected by endolymphatic hydrops. This study aimed to determine the SVV in MD patients during the chronic phase of illness compared to healthy participants. The second aim was to compare the SVV measurement tools: the analog bucket test, digital bucket test, and C-SVV© goggles. The SVV scores differed significantly between MD patients and the control group for the analog bucket test ( < 0.001) and the C-SVV goggles ( = 0.028), but no significance was shown when using the digital bucket test ( = 0.062). When comparing the analog bucket test and the C-SVV goggles applying the calculated threshold (1.125° in analog bucket test, 2.5° in C-SVV goggles), the bucket test showed higher accuracy (bucket test 73.84%, C-SVV goggles 69.23%). When examining the influence of betahistine on SVV scores, there were no statistically significant differences in both the analog bucket test and C-SVV© goggles. We conclude that SVV test can be used as an additional tool to evaluate utricle function during the chronic phase of MD and that the analog bucket test produces the most reliable results. The intake of betahistine does not influence the perception of SVV.
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http://dx.doi.org/10.3390/diagnostics11020249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915072PMC
February 2021

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

Eur Arch Otorhinolaryngol 2021 Oct 25;278(10):3941-3953. Epub 2021 Jan 25.

Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum and Campus Charité Mitte, Augustenburger Platz 1, 13353, Berlin, Germany.

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients.

Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019).

Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients.

Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.
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http://dx.doi.org/10.1007/s00405-020-06573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382606PMC
October 2021

Can nasal acetylsalicylic acid challenge predict the severity of non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD)?
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Allergol Select 2020 23;4:135-143. Epub 2020 Dec 23.

CVK Department of Otorhinolaryngology, Head and Neck Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD) complicates the clinical course of chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma. We aimed to determine the detection rate of NERD in patients with CRSwNP, asthma, and history of NSAID intolerance using nasal challenge with acetylsalicylic acid (ASA) and the relationship between the severities of response to ASA challenges and the grade of N-ERD.

Materials And Methods: Three groups of patients were included: CRSwNP with asthma and clinical history of analgesics intolerance (CRSwNP-AAI n = 18), CRSwNP with asthma but without a clinical history of analgesics intolerance (CRSwNP-A n = 20), and CRSwNP without asthma or analgesics intolerance (n = 18). All subjects were challenged nasally with 16 mg ASA and monitored with active anterior rhinomanometry. Rhinological (nasal polyp score), pulmonary (spirometry, Asthma Control Test (ACT), and asthma treatment), and psychometric questionnaire scores were recorded and correlated with rhinomanometric data following nasal challenges (flow depressions and symptom scores).

Results: Nasal ASA challenge detected N-ERD in 96.7% of CRSwNP-AAI patients and 45% of CRSwNP-A patients. No N-ERD was seen in the CRSwNP group. The control grade of asthma measured with ACT scores was significantly lower in the groups CRSwNP-AAI (MV 18.22) and CRSwNP-A (MV 19.75) when compared to the CRSwNP group (MV 24.39) (p = 0.000). In the CRSwNP-AAI group, 11 patients had uncontrolled asthma (61%), and in the CRSwNP-A group, 9 patients had uncontrolled asthma (45%). No correlation was found between rhinology and pulmonary parameters, nasal symptoms, and the severity of nasal ASA challenges. Specific reactions were detectable under the therapy of prednisolone and omalizumab.

Conclusion: N-ERD might not always be detected by screening a patient's medical history. Nasal ASA challenges are recommended in patients with CRSwNP and asthma. The nasal challenge with ASA positively confirms the N-ERD diagnosis. Moreover, N-ERD is a differential diagnosis in patients with severe asthma with the need for prednisolone or omalizumab therapy. The severity of the reaction to the ASA challenge in controlled and uncontrolled asthma patients is independent of the grade of N-ERD.
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http://dx.doi.org/10.5414/ALX01996E
DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771579PMC
December 2020

Auditory Brainstem Responses (ABR) of Rats during Experimentally Induced Tinnitus: Literature Review.

Brain Sci 2020 Nov 24;10(12). Epub 2020 Nov 24.

Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Tinnitus is a subjective phantom sound perceived only by the affected person and a symptom of various auditory and non-auditory conditions. The majority of methods used in clinical and basic research for tinnitus diagnosis are subjective. To better understand tinnitus-associated changes in the auditory system, an objective technique measuring auditory sensitivity-the auditory brainstem responses (ABR)-has been suggested. Therefore, the present review aimed to summarize ABR's features in a rat model during experimentally induced tinnitus. PubMed, Web of Science, Science Direct, and Scopus databanks were searched using Medical Subject Heading (MeSH) terms: auditory brainstem response, tinnitus, rat. The search identified 344 articles, and 36 of them were selected for the full-text analyses. The experimental protocols and results were evaluated, and the gained knowledge was synthesized. A high level of heterogeneity between the studies was found regarding all assessed areas. The most consistent finding of all studies was a reduction in the ABR wave I amplitude following exposure to noise and salicylate. Simultaneously, animals with salicylate-induced but not noise-induced tinnitus had an increased amplitude of wave IV. Furthermore, the present study identified a need to develop a consensus experimental ABR protocol applied in future tinnitus studies using the rat model.
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http://dx.doi.org/10.3390/brainsci10120901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760291PMC
November 2020

Mast Cells in the Auditory Periphery of Rodents.

Brain Sci 2020 Oct 1;10(10). Epub 2020 Oct 1.

Department of Human Medicine, MSH Medical School Hamburg, University of Applied Sciences and Medical University, 20457 Hamburg, Germany.

Mast cells (MCs) are densely granulated cells of myeloid origin and are a part of immune and neuroimmune systems. MCs have been detected in the endolymphatic sac of the inner ear and are suggested to regulate allergic hydrops. However, their existence in the cochlea has never been documented. In this work, we show that MCs are present in the cochleae of C57BL/6 mice and Wistar rats, where they localize in the modiolus, spiral ligament, and stria vascularis. The identity of MCs was confirmed in cochlear cryosections and flat preparations using avidin and antibodies against c-Kit/CD117, chymase, tryptase, and FcεRIα. The number of MCs decreased significantly during postnatal development, resulting in only a few MCs present in the flat preparation of the cochlea of a rat. In addition, exposure to 40 µM cisplatin for 24 h led to a significant reduction in cochlear MCs. The presence of MCs in the cochlea may shed new light on postnatal maturation of the auditory periphery and possible involvement in the ototoxicity of cisplatin. Presented data extend the current knowledge about the physiology and pathology of the auditory periphery. Future functional studies should expand and translate this new basic knowledge to clinics.
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http://dx.doi.org/10.3390/brainsci10100697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601519PMC
October 2020

Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.

Curr Protoc Mouse Biol 2020 Dec;10(4):e84

Department of Otorhinolaryngology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

The mouse is the most widely used animal model in hearing research. Immunohistochemistry and immunofluorescent staining of murine cochlear sections have, thus, remained a backbone of inner ear research. Since many primary antibodies are raised in mouse, the problem of "mouse-on-mouse" background arises due to the interaction between the anti-mouse secondary antibody and the native mouse immunoglobulins. Here, we describe the pattern of mouse-on-mouse background fluorescence in sections of the postnatal mouse cochlea. Furthermore, we describe a simple double-blocking immunofluorescence protocol to label mouse cochlear cryosections. The protocol contains a conventional blocking step with serum, and an additional blocking step with a commercially available anti-mouse IgG blocking reagent. This blocking technique virtually eliminates the "mouse-on-mouse" background in murine cochlear sections, while adding only a little time to the staining protocol. We provide detailed instructions and practical tips for tissue harvesting, processing, and immunofluorescence-labeling. Further protocol modifications are described, to shorten the duration of the protocol, based on the primary antibody incubation temperature. Finally, we demonstrate examples of immunofluorescence staining performed using different incubation times and various incubation temperatures with a commercially available mouse monoclonal primary antibody. © 2020 The Authors. Basic Protocol: Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.
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http://dx.doi.org/10.1002/cpmo.84DOI Listing
December 2020

Single-centre experience and practical considerations of the benefit of a second cochlear implant in bilaterally deaf adults.

Eur Arch Otorhinolaryngol 2021 Jul 5;278(7):2289-2296. Epub 2020 Sep 5.

Department of Otorhinolaryngology, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Purpose: Bilateral cochlear implant (CI) implantation is increasingly used in the auditory rehabilitation of bilaterally deafened adults. However, after successful unilateral implantation, objective patient counselling is essential.

Methods: We investigated the extra benefit of a second CI in adults in terms of health-related quality of life, tinnitus, stress, anxiety, depression, quality of hearing, and speech recognition. Hearing ability was assessed by using the Freiburg monosyllable speech discrimination test (FB MS) and the Oldenburg sentence test with azimuth variations. In a prospective patient cohort, we administered validated questionnaires before a CI, after a first CI and after a second CI implantation.

Results: The study included 29 patients, made up of nine women and 20 men. The median time between the first and the second implantation was 23 months. The mean total NCIQ score and TQ before a CI improved significantly after both implantations. Stress, anxiety, and depression were stable over time and were not significantly affected by CI implantations. Speech recognition with noise significantly improved after the first and again after the second CI. Correlation analysis showed a strong connection between auditory performance and HRQoL.

Conclusion: We demonstrated that a unilateral CI benefitted many fields and that the second sequential CI leads again to additional improvement. Bilateral CI implantation should, therefore, be the standard form of auditory rehabilitation in deafened adults.
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http://dx.doi.org/10.1007/s00405-020-06315-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165073PMC
July 2021

Incus Dislocation and Traumatic Tympanic Membrane Perforation as a Complication of Middle Cranial Fossa Repair of Tegmen Dehiscence.

Ear Nose Throat J 2020 Aug 25:145561320950595. Epub 2020 Aug 25.

Department of Otorhinolaryngology, 14903Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

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http://dx.doi.org/10.1177/0145561320950595DOI Listing
August 2020

Safety and effectiveness in explantation and re-implantation of hypoglossal nerve stimulation devices.

Eur Arch Otorhinolaryngol 2021 Feb 26;278(2):477-483. Epub 2020 Jun 26.

Department of Otorhinolaryngology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

Purpose: Since 2001, hypoglossal nerve stimulators have been implanted in patients with obstructive sleep apnea around the world, initially in trial situations but more recently also in regular care settings. Medium term data indicate effectiveness and tolerability of treatment. However, when assessing the safety of the procedure, the safe feasibility of explantation or reimplantation must also be considered.

Patients And Methods: Nine patients with an implanted respiratory-driven hypoglossal nerve stimulator. We have evaluated the feasibility and safety of explantation or re-implantation with another stimulation system.

Results: In 2012, nine patients were implanted with a respiratory-driven hypoglossal nerve stimulator as part of the Apnex Medical Pivotal Study. The study was ended in 2013. For a variety of reasons, the system was explanted from all nine patients by the year 2019. Three of these patients were re-implanted with a different system with respiratory sensing during the same session (mean incision to closure time for explantation 88.2 ± 35.01 min., mean incision to closure time for re-implantation 221.75 ± 52.73 min.). Due to extensive scar tissue formation, all procedures were technically challenging. Complication rate was significantly higher when re-implantation was performed or attempted in the same surgical session (0 of 5 patients with explantation versus 3 of 4 patients with attempted re-implantation; p = 0.018). There was no significant difference between the AHI values before and after implantation in patients with re-implantation.

Conclusion: Explantation and re-implantation are technically challenging though possible procedures. The single-staged equilateral reimplantation of another hypoglossal nerve stimulation system can, but need not, be successful.
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http://dx.doi.org/10.1007/s00405-020-06170-wDOI Listing
February 2021

COVID-19 in a patient with severe chronic rhinosinusitis with nasal polyps during therapy with dupilumab.

J Allergy Clin Immunol 2020 Jul 15;146(1):218-220.e2. Epub 2020 May 15.

Department of Otorhinolaryngology, Head and Neck Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt- Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228693PMC
July 2020

Repeat Radiation for Local Recurrence of Head and Neck Tumors and in Prostate Cancer.

Dtsch Arztebl Int 2020 Mar;117(10):167-174

Department of Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin,Campus Virchow-Klinikum; Charité CyberKnife Center Berlin, Charité-Universitätsmedizin Berlin,Campus Virchow-Klinikum; Klinik für Strahlentherapie Universitätsklinikum Leipzig; Department of Urology, Charité-Universitätsmedizin Berlin; Department of Otolaryngology, Charité-Universitätsmedizin Berlin,Campus Virchow-Klinikum.

Background: Recent advances in diagnostic methods and in radiotherapy now increasingly enable repeat radiotherapy with curative intent for the treatment of previously irradiated lesions. In this review, we present data on oncological outcomes and on acute and late sequelae, as far as these are currently known, in patients with head and neck tumors (HNT) or prostate cancer (PCa) who underwent repeat radiotherapy after prior radiotherapy with curative intent.

Methods: This review is based on clinical series with over 20 patients that were published between May 1998 and April 2018 (HNT) or between October 1998 and October 2018 (PCa) and were retrieved by a search in the PubMed database.

Results: Most of the clinical series retrieved were retrospective and uncontrolled. There were 16 studies that included 2678 patients with recurrent head and neck tumors, and 8 that included 245 patients with recurrent prostate cancer. In patients with squamous cell carcinoma of the head and neck, intensity-modulated radio - therapy (IMRT) and stereotactic body radiotherapy (SBRT) yielded three-year survival rates of 47-57% but also produced substantial acute and late adverse effects. Most of the studies concerning recurrent PCa involved small patient groups. In these studies, repeat radiotherapy with SBRT yielded tumor control rates of 40-80% after 11-24 months of follow-up, with only mild acute toxicity.

Conclusion: Although no comparative studies are available, it seems that modern external beam radiotherapy techniques can be used for repeat radiotherapy of locally recurrent head and neck tumors with curative intent after careful patient selection. Repeat radiotherapy of PCa must still be considered experimental, but initial results from small-scale trials are encouraging. The long-term adverse effects cannot yet be accessed. Patients should be selected by an interdisciplinary tumor board. This type of treatment is generally carried out in a specialized center.
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http://dx.doi.org/10.3238/arztebl.2020.0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171476PMC
March 2020

Superior Vena Cava Syndrome With Laryngeal Edema Mimicking Drug-Induced Angioedema: Implications for Otolaryngology.

Ear Nose Throat J 2020 Apr 15:145561320920745. Epub 2020 Apr 15.

Department of Otorhinolaryngology, Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

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http://dx.doi.org/10.1177/0145561320920745DOI Listing
April 2020

Digital diaphanoscopy of the maxillary sinuses: A revival of optical diagnosis for rhinosinusitis.

Am J Otolaryngol 2020 May - Jun;41(3):102444. Epub 2020 Feb 24.

BIH Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin Berlin, Berlin, Germany.

Purpose: The non-invasive diagnosis of acute rhinosinusitis (ARS) remains an unresolved problem of modern otolaryngology. Analog diaphanoscopy of reduced transillumination (shading) could be enhanced by a digital image processing of the maxillary sinuses. By this means, the limited ergonomics of this safe and low-cost method can be overcome, and merits renewed the investigation. Here, we compared the diagnostic sensitivity and specificity of digital diaphanoscopy and computed tomography (CT) in detecting shading in the maxillary sinus.

Materials And Methods: We examined 103 adults using both digital diaphanoscopy of the maxillary sinus and native-phase cranial CT. We developed a scoring system for investigation of shading in the maxillary sinus using diaphanoscopy and compared the sensitivity and specificity with that of CT. Also, we documented a follow-up of acute rhinosinusitis.

Results: In diagnosing shading in the maxillary sinus, digital diaphanoscopy had a sensitivity of 86% and a specificity of 88%. Digital diaphanoscopy can be used not only in the screening of ARS but also for documentation of its course.

Conclusion: This study supports the role of modern digital diaphanoscopy in the diagnosis of shading in the maxillary sinus, especially in patients with ARS when CT imaging is not recommended. The ergonomics of analog diaphanoscopy could be significantly improved for physicians and patients by the implementation of modern hardware and software components. Further development of the technique and the use of several discrete wavelengths will improve this method's sensitivity and specificity.
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http://dx.doi.org/10.1016/j.amjoto.2020.102444DOI Listing
September 2020

Binaural Hearing Rehabilitation Improves Speech Perception, Quality of Life, Tinnitus Distress, and Psychological Comorbidities.

Otol Neurotol 2020 06;41(5):e563-e574

Department of Otorhinolaryngology, Head and Neck Surgery, Charité - University Medical Center Berlin, Campus Virchow-Klinikum, Berlin.

Objectives: To determine and compare the benefit of binaural hearing rehabilitation via cochlear implantation (CI) on speech perception, assessment of auditory abilities, tinnitus distress, health-related quality of life (HRQoL) and psychological comorbidities in patients suffering from asymmetric hearing loss (AHL) as well as bilaterally-deafened and sequentially bilaterally-implanted patients.

Methods: 53 patients were implanted between 2011 and 2016. 24 AHL patients were implanted unilaterally, using a hearing aid on the other side. 29 bilaterally-deafened patients were sequentially implanted bilaterally. Speech perception, subjective hearing quality, HRQoL, tinnitus distress, anxiety, depressiveness, perceived stress level and coping abilities were evaluated before implantation, as well as 6 and 24 months postoperatively.

Results: Before CI, AHL and bilaterally-deaf patients showed significant differences regarding assessment of auditory abilities, speech discrimination, tinnitus distress and HRQoL. 24 months after CI both groups significantly improved in those scales. We could not find a significant difference between the groups after 2 years. Tinnitus distress significantly decreased 6 and 24 months postoperatively in both groups.

Conclusions: This study demonstrates the long-term benefit of binaural hearing rehabilitation in AHL and bilaterally-deaf patients not only regarding speech perception but also HRQoL, tinnitus distress and subjective hearing quality. Bilaterally-deafened patients present lower scores preoperatively, but they did not differ from AHL patients 2 years after CI. Up to now, this is the first study evaluating the outcome of CI in AHL patients compared to bilaterally-implanted patients and demonstrating the benefit of binaural hearing rehabilitation in these specific groups.
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http://dx.doi.org/10.1097/MAO.0000000000002590DOI Listing
June 2020

Technical, Medical and Ethical Challenges in Networks of Smart Active Implants.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:1484-1487

Networks of distributed interactive micro-implants could enhance the treatment of otoneurological conditions such as tinnitus or restore impaired complex physiological/ motor functions such as gastrointestinal motility or grasping. For this, an electrical stimulation of neural and muscular tissue is a key prerequisite. Challenges in the development of such interactive micro-implants are the complex human-machine interface, the wireless power supply, and the long-term stability of implants as well as secure and safe signal transmission. This paper addresses all these topics as well as the ethical, legal and social implications of smart implant networks in general. First achievements of the German innovation cluster INTAKT will be presented.
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http://dx.doi.org/10.1109/EMBC.2019.8856977DOI Listing
July 2019

Research platform for medical device development to simplify translation to the market

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:1452-1455

New regulations for medical products complicate research projects for new application fields and translation of innovative product ideas to refundable medical products becomes a high economic risk. All this demands for a CE-marked platform, which offers the possibility to access the recorded data online or even directly the hardware during research applications, to bridge the gap. This paper describes how a CE-marked medical product can be extended by different interfaces to enable basic research or simplify first proof-of-concept studies thus optimizing prototype development in research projects, simplifying the documentation process and reducing the risk for market access.
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http://dx.doi.org/10.1109/EMBC.2019.8857935DOI Listing
July 2019

Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials.

Lancet 2019 11 19;394(10209):1638-1650. Epub 2019 Sep 19.

Sanofi, Bridgewater, NJ, USA.

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.

Methods: LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454.

Findings: Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was -2·06 (95% CI -2·43 to -1·69; p<0·0001) in SINUS-24 and -1·80 (-2·10 to -1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was -0·89 (-1·07 to -0·71; p<0·0001) in SINUS-24 and -0·87 (-1·03 to -0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was -7·44 (-8·35 to -6·53; p<0·0001) in SINUS-24 and -5·13 (-5·80 to -4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo.

Interpretation: In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options.

Funding: Sanofi and Regeneron Pharmaceuticals.
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http://dx.doi.org/10.1016/S0140-6736(19)31881-1DOI Listing
November 2019

Extraoral Osseous Choristoma in the Head and Neck Region: Case Report and Literature Review.

Case Rep Otolaryngol 2019 28;2019:8532356. Epub 2019 May 28.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Otorhinolaryngology, Charitéplatz 1, 10117 Berlin, Germany.

An osseous choristoma is a benign tumor consisting of regular bone tissue in an irregular localization. Choristomas in the head and neck region are rare. Most frequently, they are found in the region of the tongue or oral mucosa. There are also very few reports on osseous choristomas in the submandibular region. We present the case of a woman with a large, caudal osseous choristoma within the lateral cervical triangle. Literature review is given about all of the reported cases in the region of the neck. The pathogenesis is yet unexplained. Our case supports the theory that the development of an osseous choristoma is a reaction to a former trauma. Cervical osseous choristomas are seldom, but they represent an important differential diagnosis when dealing with a cervical tumor.
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http://dx.doi.org/10.1155/2019/8532356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558603PMC
May 2019
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