The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses.

Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has so far remained controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generating and analyzing a conditional knockout mouse model allowing a targeted postnatal deletion of Snap-25 in IHCs. Mice subjected to IHC Snap-25 inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of Snap-25 in these mutant mice rescued their hearing function by restoring IHC exocytosis and preventing synapses and hair cells from degeneration. These results demonstrate that SNAP-25 is essential for normal hearing function, most likely by ensuring IHC exocytosis and ribbon synapse maintenance.

[Therapeutic strategies for upper aerodigestive tract cancers]. / Stratégies thérapeutiques dans les cancers des voies aérodigestives supérieures.

Upper aerodigestive tract squamous cell carcinomas are the most frequent head and neck cancers. They are generally associated with alcohol and tobacco, but can also be HPV-induced for the oropharynx. Their diagnosis is often late and at a locally advanced stage, making treatment more complex. After a complete primary assessment, the most suitable therapeutic sequence is proposed to the patient after a case-by-case discussion in a multidisciplinary meeting. The therapeutic arsenal for head and neck cancers is mainly composed of surgery, radiotherapy, chemotherapy, and recently immunotherapy. The latter renewed the management of patients with unresectable locoregional recurrence or metastatic.

RÉSUMÉ STRATÉGIES THÉRAPEUTIQUES DANS LES CANCERS DES VOIES AÉRODIGESTIVES SUPÉRIEURES. Les carcinomes épidermoïdes des voies aérodigestives supérieures (VADS) sont les plus fréquents des cancers de la région de la tête et du cou. Ils sont généralement associés à la consommation d'alcool et de tabac mais peuvent aussi être induits par les papillomavirus, notamment les tumeurs oropharyngées. Leur diagnostic est le plus souvent réalisé à un stade localement avancé, rendant le traitement plus complexe. Après un bilan initial complet, la séquence thérapeutique la plus adaptée est proposée au patient après une discussion au cas par cas en réunion de concertation pluridisciplinaire. L'arsenal thérapeutique des cancers des VADS est principalement composé de la chirurgie, la radiothérapie et la chimiothérapie, auxquelles s'est récemment ajoutée l'immunothérapie. Cette dernière a renouvelé la stratégie de prise en charge des patients en situation de récidive locorégionale non résécable ou en situation métastatique.

Fusobacterium necrophorum, a major provider of sinus thrombosis in acute mastoiditis: A retrospective multicentre paediatric study.

OBJECTIVE: To evaluate in children the clinical severity and evolution of otogenic lateral sinus thrombosis (OLST) due to Fusobacterium necrophorum compared with other bacterial otogenic thrombosis and propose a specific management flowchart for Fusobacterium OLST. DESIGN: A retrospective multicentre cohort study. SETTINGS: Four French ENT paediatric departments. PARTICIPANTS: A total of 260 under 18 years old admitted for acute mastoiditis were included. Initial imaging was reviewed to focus on complicated mastoiditis and 52 OLST were identified. Children were then divided into two groups according to bacteriological results: 28 in the "OLST Fusobacterium group" and 24 in the "OLST other bacteria group". RESULTS: There was a significant association between F necrophorum and OLST (P < .001). When compared to the OLST other bacteria group, children in the OLST Fusobacterium group were significantly younger (61 months vs 23 months, P < .01) and had a more severe clinical presentation: higher CRP (113 mg/L vs 175.7 mg/L, P = .02) and larger subperiosteal abscess (14 mm vs 21 mm, P < .01). Medical management was also more intensive in the OLST Fusobacterium group than in the OLST other bacteria group: increased number of conservative surgeries (66.7% vs 92.9%, P = .03) and longer hospital stay (13.7 days vs 19.8 days, P = .02). At the end of follow-up, the clinical course was good in both groups without any neurological sequelae. CONCLUSIONS: Thrombotic complications are very frequent in case of Fusobacterium mastoiditis and clinicians should be aware of the initial severity of the clinical presentation. Under appropriate management, the clinical course of Fusobacterium OLST is as good as that of other bacterial otogenic thrombosis.