Characteristics of CI children with complicated middle ear infections.

OBJECTIVE: To describe cases of complicated middle ear infections in children with cochlear implants (CI), i.e., episodes of acute otitis media (AOM) and acute mastoiditis (AM), resulting in hospitalization. METHODS: A total of 206 children under 16 years (300 implantations) were implanted between 1 January 2008 and 31 December 2014 at the West Danish CI Center, Department of Otorhinolaryngology Head and Neck Surgery, Aarhus, Denmark. By means of two prospective local databases, episodes of AOM or AM and demographics were retrieved including biochemistry, microbiology, length of follow- up, and variable treatment modalities (intravenous (IV) antibiotics, revision mastoidectomy, and insertion of ventilation tubes). RESULTS: Overall rate of AOM and/or AM was 9.2% (AOM: 9%, AM: 1.9%). Mean age at CI was 46 months. Mean follow-up was 45 months. Mean time from CI operation to AOM or AM was 3 and 4 months, respectively. Children younger than 2 years were at highest risk of AOM and/or AM. All had antibiotics prescribed before admittance, and two- thirds of infected ears had already ventilation tubes inserted. Bacteria could not be detected in more than half of cases. The most frequently isolated strains were pneumococci and nontypable Haemophilus influenzae. The majority of patients were successfully treated with IV cefuroxime (64% of cases) and insertion of ventilation tubes. None of the children developed facial nerve paralysis, intracranial infections, or septicemia. DISCUSSION: Almost 10% of CI children required at least one hospitalization due to AOM and/or AM compared with 0.1 per thousand of non-CI children. This discrepancy can be explained by a low threshold for active treatment of otitis media in CI children and hence referral to a CI center. The results suggest that benzylpenicillin might be an appropriate initial treatment of AOM and AM. However, cephalosporin was the most preferred antibiotic. Most CI children were already treated with ventilation tubes at admission and almost all children without ventilation tubes, had a tube inserted during admission. Insertion of ventilation tubes is still much debated and more research in this field is needed. CONCLUSION: AOM and/or AM were seen in Danish children with CI as often as in other western countries. Treatment of complicated middle ear infections was sufficient with IV cephalosporin and ventilation tube insertion. Special attention should be paid to children younger than 4 years and the associated microbiology including serotyping should be monitored.

The DR6 protein from human herpesvirus-6B induces p53-independent cell cycle arrest in G2/M.

HHV-6B infection inhibits cell proliferation in G2/M, but no protein has so far been recognized to exert this function. Here we identify the protein product of direct repeat 6, DR6, as an inhibitor of G2/M cell-cycle progression. Transfection of DR6 reduced the total number of cells compared with mock-transfected cells. Lentiviral transduction of DR6 inhibited host cell DNA synthesis in a p53-independent manner, and this inhibition was DR6 dose-dependent. A deletion of 66 amino acids from the N-terminal part of DR6 prevented efficient nuclear translocation and the ability to inhibit DNA synthesis. DR6-induced accumulation of cells in G2/M was accompanied by an enhanced expression of cyclin B1 that accumulated predominantly in the cytoplasm. Pull-down of cyclin B1 brought down pCdk1 with the inactivating phosphorylation at Tyr15. Together, DR6 delays cell cycle with an accumulation of cells in G2/M and thus might be involved in HHV-6B-induced cell-cycle arrest.