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Objective: Women with HIV (WWH) have an increased risk to develop recurrent cervical intraepithelial neoplasia grade 2/3 (rCIN2/3) after treatment compared with HIV-negative women. Therefore, appropriate posttreatment monitoring of WWH is important. This study evaluates the performance of ASCL1 and LHX8 methylation analysis as posttreatment monitoring test in WWH treated for CIN2/3, as alternative to cytology or human papillomavirus (HPV) as follow-up test., Design: Prospective observational cohort study., Methods: WWH treated for CIN2/3 by large loop excision of the transformation zone (LLETZ) (n  = 61) were invited for follow-up study visits at 1, 2.5 and 4 years after baseline. Baseline and follow-up cervical scrapes were tested for cytology, HPV and DNA methylation of ASCL1 and LHX8 genes. The performance of these strategies for the detection of rCIN2/3 was evaluated in the first follow-up cervical scrape., Results: Thirteen (21.3%) rCIN2/3 lesions were detected within 4 years of follow-up. In women without rCIN2/3 in follow-up, methylation levels of ASCL1 and LHX8 decreased significantly after LLETZ treatment (P  = 0.02 and 0.007, respectively). In women with rCIN2/3, methylation levels remained high after LLETZ treatment. The 4-year rCIN2/3 risk was 4.9% (95% CI: 0.6-16.5) for ASCL1/LHX8-negative women, 8.1% (95% CI: 1.7-21.9) for HPV-negative women and 7.7% (95% CI: 2.1-18.5) for cytology-negative women., Conclusion: A negative ASCL1/LHX8 methylation test in follow-up is associated with a low rCIN2/3 risk and could serve as an objective test of cure and well tolerated alternative for HPV and/or cytology screening in the posttreatment monitoring of WWH., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Results and success measures of cholesteatoma surgery are generally described using objective data whereas subjective data are mostly lacking. Patients experiences and complaints are becoming more important alongside clinical and audiometric outcome measures in cholesteatoma care., Objective: To investigate the course of patient-reported complaints, the impact of complaints, audiometric measures and the stability of audiometric measures, and complaints over time after primary and recurrent/residual cholesteatoma surgery., Methods: Postoperative patients were prospectively included and divided into primary acquired and recurrent/residual cholesteatoma. The EuroQol 5D (EQ-5D-3L), Otology Questionnaire Amsterdam (OQUA), and the Speech Spatial Questionnaire (SSQ) were completed by 144 patients up to 2 years postoperative. Patient-reported complaints divided in eight separate domains, postoperative hearing and impact on daily life were longitudinally assessed by means of linear mixed models., Results: Hearing loss and tinnitus are the most reported postoperative complaints over time. Patient-reported loss of taste and the impact of all complaints decline over time. All other patient-reported complaints remain stable over time, only itch complaints fluctuate. Primary cholesteatoma patients score significantly higher on hearing loss complaints compared with recurrent/residual patients although they have comparable mean audiometric hearing loss. Furthermore, pure-tone hearing threshold, instead of asymmetric hearing loss, is correlated with the localization domain of the SSQ., Conclusion: This study provides important insights in the course of complaints and its impact on daily life after cholesteatoma surgery. Overall, the postoperative patient-reported complaints after cholesteatoma surgery are generally low in the studied population., Competing Interests: Conflicts of Interest and Source of Funding: F.A.t.T., S.E.K., R.J.P., and P.M. were financially supported by The Netherlands Organisation for Health Research and Development (ZonMw) (grant 80-83700-9816504), Zorgverzekeraars Nederland (ZN), and Stichting Het Heinsius- Houbolt foundation. For the remaining authors none were declared., (Copyright © 2022, Otology & Neurotology, Inc.)

Objective: To determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS)., Methods: This was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase., Results: Sixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%-7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%-7.4%) or relapses (95% CI 0%-7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0-5.0) and after follow-up (3.0, IQR 2.0-5.0)., Conclusion: Personalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations., Classification of Evidence: This study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS., (© 2020 American Academy of Neurology.)

Objective: Natalizumab is effective in treating relapsing-remitting multiple sclerosis (RRMS). However, many patients report an increase of multiple sclerosis symptoms at the end of the natalizumab cycle: a wearing-off effect. The objective of this study was to evaluate the prevalence of the wearing-off effect in patients with standard and extended intervals and to study possible associations with pharmacokinetic/dynamic measurements and patient characteristics in a prospective, monocenter, cross-sectional cohort study., Methods: Patients with RRMS, with a minimum of 6 natalizumab infusions, were asked to complete 3 questionnaires: the Multiple Sclerosis Impact Scale, the 36-Item Short Form Health Survey, and a general questionnaire regarding the wearing-off effect. Natalizumab concentration and α4-integrin receptor saturation were measured before redosing., Results: Ninety-three patients were included. A total of 54% experienced a wearing-off effect during natalizumab treatment and 32% experienced a current wearing-off effect at time of measurement. The self-reported wearing-off effect was not associated with natalizumab concentration nor with α4-integrin receptor saturation. The wearing-off effect was more frequently reported in the standard interval group (39%) than in the extended interval group (19%); the duration of symptoms was comparable between both groups. The wearing-off effect was not associated with number of infusions, disease duration, age, or sex., Conclusion: The wearing-off effect is a frequently reported phenomenon but is unlikely to reflect a nonoptimal pharmacokinetic/dynamic state. We did not find risk factors predicting the wearing-off effect., (© 2019 American Academy of Neurology.)

Background: Genotype attribution in high-grade cervical lesions (CIN3+) can be calculated by the hierarchical or proportional method, but these do not account for the genotype distribution in the general population and cannot assess the number of genotype-specific high-grade cervical lesions (CIN3+)., Methods: We present a statistical method for estimating genotype-specific CIN3+ risks and genotype attribution in CIN3+ from cervical screening samples. A key assumption is that genotype-specific infections in women with multiple infections have independent progression risks. We applied the method to 512 human papillomavirus (HPV)-positive women referred for colposcopy and validated it by laser-capture microscopy-polymerase chain reaction. We also compared performance by simulation., Results: For endpoint CIN3+, the summed deviation of attributable fractions between the estimated genotype-specific attributable fractions and laser-capture microscopy polymerase chain reaction-based attributable fractions was similar for the three methods: 0.17 for the new method (95% confidence interval [CI] = 0.091, 0.28), 0.19 (95% CI = 0.11, 0.33) for the hierarchical method and 0.15 (95% CI = 0.085, 0.26) for the proportional method. Simulations indicated that the new method outperformed the other methods for endpoint CIN3+ when the number of HPV-positive women was large. Exclusion of HPV16-positive women had only a small effect on the estimated genotype-specific risks, supporting the independence assumption., Conclusions: Genotype-specific attribution in CIN3+ can be accurately predicted by a model that assumes independence between genotypes with respect to disease progression. The method can be used to monitor HPV vaccine effectiveness for prevention of genotype-specific CIN3+ and to assess disease risk after vaccination.

Objective: Objective evaluation of the efficacy of tongue lip adhesion (TLA) in the management of Robin sequence (RS)., Study Design: Retrospective cohort study., Setting: Tertiary referral hospital., Patients, Participants: The craniofacial database of Amsterdam UMC, Vrije Universiteit Amsterdam was searched to identify infants with RS who underwent tong lip adhesion (TLA). Forty-one RS infants who underwent TLA from 1993 to 2016 were identified., Interventions: TLA., Main Outcome Measure: The outcome measures were pre- and postoperative polysomnography results, nutritional status, weight gain, age at operation, hospital stay length, extubation time after TLA, and complications., Results: Forty-one RS patients were included who had TLA at an average age of 26.6 days. In 16 cases a pre- and postoperative polysomnography was performed. In 13 of these cases (81.3%) improvement was observed, in 2 (12.5%) the results were inconclusive, and in 1 (6.3%) no improvement was seen. Patients were extubated after a mean of 2.2 days.The mean hospital stay was 40.2 days. Reintervention was needed in 7 patients because of a wound dehiscence. The mean age of TLA release was 9.7 months. At discharge, 9 (22%) children still needed total nutritional support for persistent feeding difficulties. The average growth from birth to adhesion release was 4.6 kg., Conclusion: This cohort demonstrates that TLA is a successful procedure in children with RS in terms of respiratory, feeding, and growth outcome. Only minor complications were seen in our cohort.

Objective: In the work-up of patients presenting with a clinically isolated syndrome (CIS), 3T MRI might offer a higher lesion detection than 1.5T, but it remains unclear whether this affects the fulfilment of the diagnostic criteria for multiple sclerosis (MS)., Methods: We recruited 66 patients with CIS within 6 months from symptom onset and 26 healthy controls in 6 MS centers. All participants underwent 1.5T and 3T brain and spinal cord MRI at baseline according to local optimized protocols and the MAGNIMS guidelines. Patients who had not converted to MS during follow-up received repeat brain MRI at 3-6 months and 12-15 months. The number of lesions per anatomical region was scored by 3 raters in consensus. Criteria for dissemination in space (DIS) and dissemination in time (DIT) were determined according to the 2017 revisions of the McDonald criteria., Results: Three-Tesla MRI detected 15% more T2 brain lesions compared to 1.5T ( p < 0.001), which was driven by an increase in baseline detection of periventricular (12%, p = 0.015), (juxta)cortical (21%, p = 0.005), and deep white matter lesions (21%, p < 0.001). The detection rate of spinal cord lesions and gadolinium-enhancing lesions did not differ between field strengths. Three-Tesla MRI did not lead to a higher number of patients fulfilling the criteria for DIS or DIT, or subsequent diagnosis of MS, at any of the 3 time points., Conclusion: Scanning at 3T does not influence the diagnosis of MS according to McDonald diagnostic criteria., (© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)