Association of plexiform and diffuse neurofibromas with malignant peripheral nerve sheath tumor in NF I patients: a whole-body MRI assessment.

OBJECTIVE: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs). MATERIALS AND METHODS: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs. RESULTS: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis. CONCLUSION: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors.

Double-pass consistency for amplitude- and frequency-modulation detection in normal-hearing listeners.

Amplitude modulation (AM) and frequency modulation (FM) provide crucial auditory information. If FM is encoded as AM, it should be possible to give a unified account of AM and FM perception both in terms of response consistency and performance. These two aspects of behavior were estimated for normal-hearing participants using a constant-stimuli, forced-choice detection task repeated twice with the same stimuli (double pass). Sinusoidal AM or FM with rates of 2 or 20 Hz were applied to a 500-Hz pure-tone carrier and presented at detection threshold. All stimuli were masked by a modulation noise. Percent agreement of responses across passes and percent-correct detection for the two passes were used to estimate consistency and performance, respectively. These data were simulated using a model implementing peripheral processes, a central modulation filterbank, an additive internal noise, and a template-matching device. Different levels of internal noise were required to reproduce AM and FM data, but a single level could account for the 2- and 20-Hz AM data. As for FM, two levels of internal noise were needed to account for detection at slow and fast rates. Finally, the level of internal noise yielding best predictions increased with the level of the modulation-noise masker. Overall, these results suggest that different sources of internal variability are involved for AM and FM detection at low audio frequencies.

Impact of nasalis muscle repair in unilateral cleft lip patients.

BACKGROUND: Although the role of nasalis muscle in the establishment of nasal deformity is well recognized; its abnormal anatomy and role in the correction of alar deformity in cleft lip patients have not been adequately studied. This work aimed to study the effect of nasalis muscle repair on the postoperative nasal symmetry. PATIENTS AND METHODS: A controlled prospective randomized study was conducted on 45 cases of unilateral complete pre-alveolar cleft. Patients were divided into two groups; Group 1 (repair of the Orbicularis muscle only), Group 2 was further divided into 2 subgroups: Subgroup A (repair of the orbicularis oris muscle and dissection and repair the origin of the nasalis muscle). Subgroup B (repair of the orbicularis oris muscle and dissection of both origin and abnormal insertion of the nasalis and repair of the origin). Evaluation was conducted both subjectively and objectively through cleft lip evaluation profile and nostril angles measurement. RESULTS: Group 2B patients showed significantly better shape and symmetry of nasal tip, size and symmetry of nostrils and size, form and lateral displacement of the ala. Objective evaluation showed that group 2B had the closest results to the non-cleft side, with statistically significant difference, when compared to other groups. CONCLUSION: Dissection and repair of both origin and insertion of nasalis muscle produced a nasal width, columellar height, and nasal tip projection close to the normal population of the same age.

Isotretinoin exposure during pregnancy: assessment of spontaneous reports in France.

BACKGROUND: In three previous studies, we have shown that pregnant women were still being exposed to isotretinoin and that compliance with recommendations was incomplete. The relaxation of these recommendations (summary of product characteristics 2004), combined with the release of generic brands, encouraged us to carry out a fourth study. OBJECTIVE: To assess isotretinoin exposure during pregnancy following the application of less stringent recommendations and the marketing of generic isotretinoin brands. METHODS: All cases of isotretinoin exposure during pregnancy, between 1 January 2003 and 31 December 2006, spontaneously reported to pharmacovigilance centres, the Teratogenic Agent Information Centre, and pharmaceutical companies in France were assessed. Cases were classified for analysis into the following groups: 'conception <1 month after isotretinoin discontinuation', 'conception during isotretinoin treatment' and 'patient already pregnant when isotretinoin was started'. The rate of spontaneously reported isotretinoin exposure during pregnancy was estimated by dividing the number of isotretinoin-exposed pregnancies by the number of women of childbearing age treated with isotretinoin. RESULTS: Over 4 years, 147 cases of isotretinoin exposure during the teratogenic risk period were spontaneously reported, i.e. 'conception <1 month after isotretinoin discontinuation' (23%), 'conception during isotretinoin treatment' (61%), and 'patient already pregnant when isotretinoin was started' (16%). Nineteen percent of the patients did not use any form of contraception. In 23% of the patients, the method of contraception used did not comply with recommendations, while in 86% of the cases, isotretinoin was prescribed by a dermatologist. Among the 44 pregnancies with available data on fetuses or neonates, there were two (4.5%) malformations compatible with the time of exposure and with isotretinoin embryopathy. The rate of spontaneously reported isotretinoin exposure during pregnancy has increased by approximately 30%, from 0.32 (95% CI 0.26, 0.38) to 0.41 (95% CI 0.34, 0.49) per 1000 women of childbearing age treated since 1999-2002. CONCLUSIONS: We suggest that recommendations be tightened, with specific information regarding the most effective contraceptive method combined with compulsory monthly pregnancy testing during treatment. The French Drug Agency has informed the European Medicines Agency of the need for measures aimed at improving compliance.