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Objective: To evaluate the benefit of cochlear implantation in patients with Pendred syndrome., Design: Retrospective study., Setting: Tertiary centre., Participants and Main Outcome Measures: Speech perception was measured using a phonetically balanced word list at a sound pressure level of 65 dB. Post-operative phoneme scores at 12-month for adults and 36-month for children with Pendred syndrome were compared to scores of patients with an enlarged vestibular aqueduct (EVA) and a reference group with an unknown cause of hearing impairment. Quality of life was measured with the Nijmegen Cochlear Implant Questionnaire to evaluate the differences between pre- and post-implantation., Results: The mean post-operative phoneme scores were as follows: in the Pendred group, 91% (n = 16; SD = 10) for children and 78% (n = 7; SD = 14) for adults; in the reference group, 79% (n = 59; SD = 20) for children and 73% (n = 193; SD = 18) for adults; and in the EVA group, 84% (n = 6; SD = 7) for children and 66% (n = 12; SD = 22) for adults. A significant difference in speech perception was found between the children of the Pendred group and the reference group of 11.4% (SE = 5.2; P = 0.031). Between the adults, a difference of 11.2% (SE = 6.7; P = 0.094) was found. The difference between the Pendred group and the EVA group was 5.7%(SE = 4.5; P = 0.22) for children and 9.9% (SE = 8.7; P = 0.28) for adults. A significant improvement post-implantation in four of the six subdomains of the quality of life questionnaire was found: basic sound perception (P = 0.002), advanced sound perception (P = 0.004), speech production (P = 0.018) and activity limitations (P = 0.018). The two not significant subdomains were self-esteem (P = 0.164) and social interaction (P = 0.107)., Conclusions: After cochlear implantation, children with Pendred syndrome performed better than the reference group with respect to speech perception, however, adults performed similar. No significant differences were found between the Pendred and EVA group. Consequently, during pre-operative counselling, the two groups of patients may be considered comparable in terms of expected speech perception performance after cochlear implantation., (© 2015 John Wiley & Sons Ltd.)

Objective: To analyse the benefit of cochlear implantation in young deaf children with Waardenburg syndrome (WS) compared to a reference group of young deaf children without additional disabilities., Method: A retrospective study was conducted on children with WS who underwent cochlear implantation at the age of 2 years or younger. The post-operative results for speech perception (phonetically balanced standard Dutch consonant-vocal-consonant word lists) and language comprehension (the Reynell Developmental Language Scales, RDLS), expressed as a language quotient (LQ), were compared between the WS group and the reference group by using multiple linear regression analysis., Results: A total of 14 children were diagnosed with WS, and 6 of them had additional disabilities. The WS children were implanted at a mean age of 1.6 years and the 48 children of the reference group at a mean age of 1.3 years. The WS children had a mean phoneme score of 80% and a mean LQ of 0.74 at 3 years post-implantation, and these results were comparable to those of the reference group. Only the factor additional disabilities had a significant negative influence on auditory perception and language comprehension., Conclusions: Children with WS performed similarly to the reference group in the present study, and these outcomes are in line with the previous literature. Although good counselling about additional disabilities concomitant to the syndrome is relevant, cochlear implantation is a good rehabilitation method for children with WS., (© 2016 S. Karger AG, Basel.)

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mutation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlying WS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants., (Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Aims: We aim to investigate the association between different types of statins, in particular simvastatin and atorvastatin, and long-term mortality after percutaneous coronary intervention (PCI)., Methods and Results: Between 2000 and 2005, a prospective cohort was constituted of 5,647 patients who underwent PCI. Type and doses of statin use were collected after the PCI procedure. Survival status was obtained from municipal civil registries. The primary endpoint was all-cause mortality. Secondary endpoints were cardiac and cancer mortality. Median follow-up was 5.0 years (range three to nine years). During follow-up 738 patients (13.1%) died. In total, 4,970 patients (88%) were on statin therapy four weeks after PCI of whom the majority used either atorvastatin (34%) or simvastatin (29%). Cumulative survival rates at eight years in the atorvastatin group were 83%, and 79% in the simvastatin group (log-rank, p=0.004). After adjustment, statin use was associated with a 50% mortality reduction (HR 0.49, 95% CI 0.40-0.59) and atorvastatin use was associated with lower total mortality than simvastatin use (adjusted HR 0.77, 95% CI 0.61-0.97). This was largely driven by cancer mortality (adjusted HR 0.59, 95% CI 0.38-0.91)., Conclusions: In patients undergoing PCI the use of statins is associated with reduced mortality during prolonged follow-up. Patients using atorvastatin had a 23% lower mortality than those using simvastatin.

Aims: To assess the long-term outcome of patients who underwent radioactive stent (RS) implantation., Methods and Results: The RS study population consisted of 133 consecutive patients who underwent RS implantation between November 1997 and July 2000. They were matched using the propensity score method with 266 patients who underwent bare metal stenting (BMS) in the same span. Long-term survival status and information on MACE (death, non-fatal myocardial infarction or any re-intervention) was retrospectively obtained. Eight-year cumulative survival (90.2% vs. 87.4%, p = 0.57) was similar between the RS and BMS group respectively, while 8-year cumulative MACE-free survival was significantly lower in RS patients (42.1% vs. 64.3%, p < 0.001) due to the difference in events (mainly target lesion revascularisations [TLRs]) during the first year of follow-up (cumulative 1-year MACE-free survival: 59.4% vs. 86.7%, p < 0.001); there was no difference in the MACE rate after the first year (p = 0.71). The TLR rate at six months in the RS group was 29.3%, mainly due to edge restenosis and at one year 36.2% (control group: 9.5%, p < 0.001)., Conclusions: A high incidence of MACE and re-intervention was observed during the first year following RS implantation, mainly related to TLR for edge restenosis. After the first year, the clinical outcome of RS patients was similar to the control group indicating that there are no late adverse effects related to low dose-rate intracoronary radiation therapy.

Background: Health status has become increasingly important as an outcome measure in patients with cardiovascular disease. Poor patient-rated health status has been shown to predict mortality in patients with coronary artery disease and heart failure. In patients treated with percutaneous coronary intervention (PCI), we examined whether poor health status predicts 6-year mortality and whether a decline in health status is associated with adverse clinical outcome., Methods: Consecutive patients (N = 872) treated with PCI as part of the RESEARCH registry, completed the 36-item Short-Form Health Survey (SF-36) at 1 and 12 months post-PCI., Results: The SF-36 domains physical functioning (hazard ratio [HR] 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) were associated with 6-year mortality. A decline in health status was not related with higher 6-year mortality., Conclusions: Health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. In contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting.

Purpose: We examined the association between negative and positive affect and 12-month health status in patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents., Methods: Consecutive PCI patients (n = 562) completed the Global Mood Scale at baseline to assess affect and the EuroQoL-5D (EQ-5D) at baseline and 12-month follow-up to assess health status., Results: Negative affect [F(1, 522) = 17.14, P < .001] and positive affect [F(1, 522) = 5.11, P = .02] at baseline were independent associates of overall health status at 12-month follow-up, adjusting for demographic and clinical factors. Moreover, there was a significant interaction for negative by positive affect [F(1, 522) = 6.11, P = .01]. In domain-specific analyses, high negative affect was associated with problems in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with the risk being two to fivefold. Low positive affect was only associated with problems in self-care (OR: 8.14; 95% CI: 1.85-35.9; P = .006) and usual activities (OR: 1.87; 95% CI: 1.17-3.00; P = .009)., Conclusions: Baseline negative and positive affect contribute independently to patient-reported health status 12 months post PCI. Positive affect moderated the detrimental effects of negative affect on overall health status. Enhancing positive affect might be an important target to improve patient-centered outcomes in coronary artery disease.