Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (ARSG) gene have been reported to underlie USH type IV. This distinct type of USH is characterized by late-onset RP with predominantly pericentral and macular changes, and late onset SNHL without vestibular dysfunction. In this study, we describe the USH type IV phenotype in three unrelated subjects. We identified three novel pathogenic variants, two novel likely pathogenic variants, and one previously described pathogenic variant in ARSG. Functional experiments indicated a loss of sulfatase activity of the mutant proteins. Our findings confirm that ARSG variants cause the newly defined USH type IV and support the proposed extension of the phenotypic USH classification.

Background Tinnitus is a phantom sensation of sound, which can have a negative impact on quality of life of those affected. No curative treatments are currently known. Neuromodulation by vagus nerve stimulation has emerged as a new treatment option for tinnitus, though till date the effectiveness remains unclear. Therefore, we aim to review the effect of vagus nerve stimulation on tinnitus distress and tinnitus symptom severity in patients with chronic tinnitus. Methods We searched Pubmed, Embase and the Cochrane Library systematically for RCTs, observational studies and case studies on the effect of VNS treatment for tinnitus on October 29, 2019. Studies including adult patients with subjective tinnitus, comparing transcutaneous or implantable VNS to placebo or no treatment or before and after application of VNS treatment on tinnitus distress and tinnitus symptom severity measured with a validated questionnaire were eligible. The risk of bias was assessed with the appropriate tool for each type of study. Results Our search identified 9 primary studies of which 2 RCTs, 5 cohort studies and 2 case series or reports. 5 studies used transcutaneous VNS treatment and 4 used implanted VNS treatment. 6 studies combined VNS treatment with sound therapy. There was a serious risk of bias in all studies, especially on confounding. Most studies reported a small decrease in tinnitus distress or tinnitus symptom severity. Conclusion Due to methodological limitations and low reporting quality of the included studies, the effect of VNS on tinnitus remains unclear. To draw conclusions for which patient population and to what extent (t)VNS is beneficial in the treatment of tinnitus, a randomised controlled trial should be considered.

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WHAT THIS PAPER ADDS This study shows that hybrid revascularisation is feasible and safe in symptomatic patients with an extracranial carotid artery tandem stenosis. This study provides data on purely symptomatic patients including a long-term clinical and imaging follow up period of more than six years. In the future, these surgical outcomes need to be offset against the natural course in patients with a symptomatic carotid tandem lesion. Objectives: Carotid tandem lesions are a multilevel significant (>50%) atherosclerotic disease involving both the internal carotid artery (ICA) and either the ipsilateral common carotid artery (CCA) or the innominate artery (IA). These lesions may be challenging to treat. Current guidelines offer no definitive recommendation on the optimal treatment algorithm. The aim of this analysis was to assess the long-term outcome of patients undergoing surgical revascularisation for tandem lesions. Methods: In two centres, consecutive patients who underwent carotid endarterectomy (CEA) for a symptomatic carotid artery stenosis between 2003 and 2017 were screened retrospectively for the presence of a carotid artery tandem lesion. All eligible patients were treated by a hybrid approach, consisting of retrograde stenting of the proximal CCA or IA followed by CEA. All patients had a yearly clinical check up including duplex ultrasound. The primary outcome was occurrence of any stroke, death, myocardial infarction (MI), or transient ischaemic attack (TIA) within 30 days. Secondary outcomes were any stroke, death, MI, or TIA and occurrence of restenosis 50% during follow up. Results: Sixteen of 2368 symptomatic patients were included. Besides a high grade ICA stenosis, patients had a significant ipsilateral stenosis of the CCA (n ¼ 13) or IA (n ¼ 3). Within 30 days there were no deaths, strokes, or TIAs. Two patients had a clinical MI. During a median follow up of 73 (interquartile range 22e85) months, three patients died. One patient developed a symptomatic restenosis of the ICA (ipsilateral TIA). Two patients (without restenosis) developed an ipsilateral stroke and a MI. Conclusions: In this small case series, hybrid revascularisation of carotid tandem lesions in symptomatic patients seems feasible and safe. Long-term data show a relatively high number of any adverse events. These surgical outcomes need to be offset against the natural course in patients with a symptomatic carotid tandem lesion.

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Background: Spin refers to reporting practices that could distort the interpretation and mislead readers by being more optimistic than the results justify, thereby possibly changing the perception of clinicians and influence their decisions. Because of the clinical importance of accurate interpretation of results and the evidence of spin in other research fields, we aim to identify the nature and frequency of spin in published reports of tinnitus randomized controlled trials (RCTs) and to assess possible determinants and effects of spin.Methods: We searched PubMed systematically for RCTs with tinnitus-related outcomes published from 2015 to 2019. All eligible articles were assessed on actual and potential spin using prespecified criteria.Results: Our search identified 628 studies, of which 87 were eligible for evaluation. A total of 95% of the studies contained actual or potential spin. Actual spin was found mostly in the conclusion of articles, which reflected something else than the reported point estimate (or CI) of the outcome (n = 34, 39%) or which was selectively focused (n = 49, 56%). Linguistic spin (“trend,” “marginally significant,” or “tendency toward an effect”) was found in 17% of the studies. We were not able to assess the association between study characteristics and the occurrence of spin due to the low number of trials for some categories of the study characteristics. We found no effect of spin on type of journal [odds ratio (OR) −0.13, 95% CI −0.56–0.31], journal impact factor (OR 0.17, 95% CI −0.18–0.51), or number of citations (OR 1.95, CI −2.74–6.65).Conclusion: There is a large amount of spin in tinnitus RCTs. Our findings show that there is room for improvement in reporting and interpretation of results. Awareness of different forms of spin must be raised to improve research quality and reduce research waste.

BackgroundA 12-nucleotideRIPOR2in-frame deletion was recently identified as a relatively common and highly penetrant cause of autosomal dominant non-syndromic sensorineural hearing loss, type DFNA21, in the Netherlands. The associated hearing phenotype is variable. The allele frequency (AF) of 0.039% of this variant was determined in a local cohort, and the reported phenotype may be biased because studied families were identified based on index patients with hearing loss (HL). In this study, we determine the AF in a cohort from a different geographical region of the Netherlands. Additionally, we examine the hearing phenotype in individuals with the variant but not selected for HL.MethodsThe AF was determined in participants of the Rotterdam Study (RS), a large cohort study. The phenotype was characterised using individual clinical hearing data, including audiograms.ResultsThe observed AF in the RS cohort was 0.072% and not statistically significantly different from the previously observed 0.039%. The AF in the two cohorts combined was 0.052%. Consistent with previous findings, we found a highly variable audiometric phenotype with non-penetrance of HL in 40% of subjects aged 55–81, which is higher than the 10% at age 50 previously observed.ConclusionWe found an overall higher AF and lower penetrance than previously reported, confirming that DFNA21 is relatively common in the Netherlands. This supports its potential suitability as a target for therapeutic development. Studying possible modifying factors is essential to explain the phenotypical variability and to identify patients eligible for such a therapy.

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