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Objective: In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Here, we evaluate a four‐generation family linked to a novel SDHB gene variant with the manifestation of a HNPGL. Design: A family‐based study. Setting: The VU University Medical Center (VUmc) Amsterdam, a tertiary clinic for Otolaryngology and Head and Neck Surgery. Participants and main outcome measures: The index patients presented with an embryonic rhabdomyosarcoma and a non‐Hodgkin lymphoma. Array‐based comparative genomic hybridisation (aCGH) analysis and multiplex ligation‐dependent probe amplification (MLPA) revealed a novel deletion of exon 1‐3 in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Subsequently, genetic counselling and DNA testing were offered to all family members at risk. Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO. Results: The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon 1‐3 deletion in the SDHB gene. One carrier was diagnosed with a carotid body PGL and serum catecholamine excess, which was surgically excised. Negative SDHB immunostaining of the carotid body tumour confirmed that it was caused by the SDHB variant. The remaining 9 carriers showed no evidence of PGL/PHEO. Conclusion: Deletion of exon 1‐3 in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL. [ABSTRACT FROM AUTHOR]

Germline mutations in succinate dehydrogenase B ( SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma ( PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+ 1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori cure rates vary in different geographical regions because of differences in hosts as well as in H. pylori strains. Objective: To review systematically all available data in the literature to determine H. pylori eradication rates in The Netherlands. Methods: A search of all published trials on H. pylori eradication therapy performed in The Netherlands was conducted via electronic database search, hand-searching of abstracts from scientific meetings and checking reference lists of pharmaceutical companies. Full papers and abstracts were included. Data on anti-H. pylori therapies were pooled based on duration and combination of drugs. Only triple and quadruple eradication regimens were studied. Dual therapies were excluded, except for ranitidine bismuth citrate-based dual therapies. Results: We analysed 38 study arms, involving 2197 patients. Twenty different pooled regimens were studied with a mean intention-to-treat eradication rate of 83% (range 35-96%). There were no significant differences in the percentage of patients that stopped treatment due to adverse events between the groups. In these pooled regimens only bismuth combined with tetracycline and metronidazole for 1 or 2 weeks was significantly lower in efficacy in metronidazole-resistant strains than in metronidazole-sensitive strains. The prevalence of metronidazole-resistant strains in The Netherlands showed large regional differences (7-50%). Conclusions: A therapy should be tested in a defined population before becoming standard. Several eradication regimens studied in The Netherlands yield acceptable cure rates of 80% or more on an intention-to-treat basis. We advise taking the local prevalence of metronidazole resistance into account when choosing a first-line eradication regimen. [ABSTRACT FROM AUTHOR]

The increasing antimicrobial resistance among pathogens frequently isolated from patients with bacterial meningitis formed the rationale to perform a surveillance study to determine the prevalence of resistance in The Netherlands. Haemophilus influenzae strains (n=316) isolated from cerebrospinal fluid (CSF), 1125 meningococcal strains isolated from blood or CSF and 398 pneumococcal strains isolated from CSF in 1993 and 1994 were tested by the Etest for susceptibility to commonly prescribed antibiotics for the treatment of community-acquired meningitis. In H. influenzae strains ampicillin-resistance occurred in 7.0%, resistance to chloramphenicol in 2.2%, and resistance to both antibiotics in 0.9%. The prevalence of intermediate penicillin-resistance in meningococci was 3.3%. Resistance to rifampicin was rarely found (0.1%). Intermediate penicillin-resistance in pneumococci was found in only 0.5% of isolates. All 1839 isolates were susceptible to ceftriaxone. Based on these results, we conclude that empirical therapy of childhood community-acquired bacterial meningitis with amoxycillin and chloram phenicol is no longer justified in children who have not been vaccinated against H. influenzae type b. In vaccinated or older children and adults, amoxycillin is a rational choice for empirical treatment of meningitis. The prophylactic use of rifampicin in contacts of patients with meningococcal disease is still applicable. [ABSTRACT FROM PUBLISHER]

In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin susceptibility was additionally tested for N. meningitidis. Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin. One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin. All strains were susceptible to meropenem. We conclude that meropenem is in vitro highly active against N. meningitidis and S. pneumoniae. [ABSTRACT FROM AUTHOR]

Objectives: Patient-reported experience measures (PREMs) can be used for the improvement of quality of care. In this study, the outcome of an open-ended question PREM combined with computer-assisted analysis is compared to the outcome of a closed-ended PREM questionnaire., Methods: This survey study assessed the outcome of the open-ended questionnaire PREM and a close-ended question PREM of patients with unilateral vestibular schwannoma in a tertiary vestibular schwannoma expert centre., Results: The open-ended questions PREM, consisting of five questions, was completed by 507 participants and resulted in 1508 positive and 171 negative comments, categorised into 27 clusters. The close-ended questions PREM results were mainly positive (overall experience graded as 8/10), but did not identify specific action points. Patients who gave high overall scores (>8) on the close-ended question provided points for improvement in the open-ended question PREM, which would have been missed using the close-ended questions only., Conclusions: Compared to the close-ended question PREM, the open-ended question PREM provides more detailed and specific information about the patient experience in the vestibular schwannoma care pathway., Innovation: Automated analysis of feedback with the open-ended question PREM revealed relevant insights and identified topics for targeted quality improvement, whereas the close-ended PREM did not., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective  The aim of this study was to assess the ability to smile following a hypoglossal-facial nerve transfer (N12-N7). Design  This is a retrospective chart review. Setting  National tertiary referral center for skull base pathology. Participants  Seventeen patients. Main Outcome Measures  The ability to smile following an N12-N7 transfer was assessed by five medical doctors on photographs of the whole face and frontal, orbital, and oral segments. The (segmented) photographs were scored for the symmetry, asymmetry, and correct or incorrect assessment of the affected side. Results  Seventeen patients were analyzed by 5 assessors providing 85 assessments. The whole face at rest was judged symmetrical in 26% of the cases and mildly asymmetrical in 56%. Frontal, orbital, and oral segments were symmetrical in 63, 20, and 35%, respectively. The affected side was correctly identified in 76%. When smiling, the whole face was symmetrical in 6% and mildly asymmetric in 59%. The affected side was correctly identified in 94%. The frontal, orbital, and oral segments during smiling were symmetrical in 67, 15, and 6%, respectively. The affected side of the frontal, orbital, and buccal facial segments during smiling was correctly identified in 89, 89, and 96%, respectively. Interobserver variability with Fleiss' kappa analysis showed that the strength of the agreement during smile of the total face was good (0.771) Conclusion  Following an N12-N7 transfer, a good facial symmetry at rest can be achieved. During smiling, almost all patients showed asymmetry of the face, which was predominantly determined by the orbital and oral segments. To improve the ability to smile after an N12-N7 transfer, additional procedures are needed., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: To evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA)., Study Design: Multicenter retrospective cohort study., Setting: Three tertiary otology and audiology referral centers., Patients and Diagnostic Interventions: A total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry., Mean Outcome Measures: Radiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results., Results: All patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%., Conclusion: About a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using PubMed, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the clinically relevant abnormalities as visualized on CT and MR imaging in children with symmetric and asymmetric bilateral sensorineural hearing loss (SNHL), in relation to age and the severity of hearing loss., Study Design: Retrospective cohort study., Setting: Tertiary referral otology and audiology center., Patients and Diagnostic Interventions: From January 2006 until January 2016, a total of 207 children diagnosed with symmetric and asymmetric bilateral SNHL were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss., Main Outcome Measures: Radiologic abnormalities associated with SNHL., Results: 302 scans were performed in 207 children (median age of 0.8 years old) with bilateral SNHL. The most frequently identified cause of bilateral SNHL was a malformation of the labyrinth. The combined diagnostic yield of CT and MR imaging was 32%. The diagnostic yield of MR (34%) was considerably higher than that of CT (20%). We found a higher rate of abnormalities in children with profound hearing loss (41%) compared to milder hearing loss (8-29%), and in asymmetric SNHL (52%) compared to symmetric SNHL (30%)., Conclusion: Imaging is essential in the etiologic evaluation of children with bilateral SNHL. The highest diagnostic yield is found in children with bilateral asymmetric SNHL or profound SNHL. Based on our findings, MR is the primary imaging modality of choice in the etiological evaluation of children with bilateral SNHL because of its high diagnostic yield., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Evaluation of causal abnormalities identified on CT and MR imaging in children with unilateral sensorineural hearing loss (USNHL), and the association with age and severity of hearing loss., Study Design: Retrospective cohort study., Setting: Tertiary referral otology/audiology center., Patients and Diagnostic Interventions: 102 children diagnosed with USNHL between 2006 and 2016 were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss., Main Outcome Measures: Radiologic abnormalities of the inner ear and brain associated with USNHL., Results: Using CT and/or MR imaging, causal abnormalities were identified in 49%, which is higher than previously reported (25-40%). The most frequently affected site was the labyrinth (29%), followed by the cochlear nerve (9%) and brain (7%). No significant difference in the number or type of abnormalities was found for the degree of hearing loss or age categories., Conclusions: Imaging is essential in the etiologic analysis of USNHL because of the high prevalence of causative abnormalities that can be identified with radiology, irrespective of the patients' age or degree of hearing loss. CT and MR imaging are complementary imaging options. The ideal imaging algorithm is controversial. Based on our findings, we conclude that there is limited additional diagnostic value of simultaneous dual modality imaging over sequential diagnostics. We therefore perform a stepwise radiological workup in order to maximize the diagnostic yield while minimizing impact and costs. If the primary imaging modality does not identify a cause for USNHL, performing the alternative imaging modality should be considered., Level of Evidence: Retrospective cohort study 2b., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the laser assisted ratio analyser (LARA) system for detection of Helicobacter pylori infection in breath samples., Design: Descriptive., Method: Diagnostic gastroscopy with biopsies for histopathology and culture was performed in consecutive dyspeptic patients in the Department of Gastroenterology of the Academic Medical Centre of Amsterdam in January-May 1996. Subsequently, a LARA test was carried out, which measures the degradation by H. pylori of 13C urea using the ratio of 12CO2/13CO2 in the exhaled air. The combination of the results of the examination of gastric biopsies was regarded as the golden standard for the demonstration of H. pylori infection. After this comparison, the cut-off level above which the LARA system demonstrated H. pylori infection was established in the basis of a receiver operator characteristics (ROC) analysis. An area was defined round this value within which the results were inconclusive and outside of which the reliability increased., Results: 208 patients were included in the study; the data of nine of them could not be analysed (CO2 level in the exhaled air too low: 8; withdrawal: 1). The remaining 199 patients were 105 males and 94 females with a mean age of 48 years (range 19-75). Ninety-three of them (47%) were H. pylori positive according to the golden standard. With the breath analysis infection was detected in 86 of them, while in 97 patients breath analysis was correctly negative; it was false-negative in four, false-positive in three and unreliable in nine patients. The sensitivity was 96%, the specificity 97%. The positive and negative predictive values were 97% and 96%, respectively.