BackgroundAcute otitis media (AOM) is one of the most common forms of bacterial infection and cause for clinic visits in children. The incidence of AOM was 0.9–1.2 episodes per person-year during the first 2 years of life in previous reports conducted before 2000. The aim of this study was to 1) evaluate the latest AOM incidence in pediatric outpatients and 2) identify the bacterial pathogens from these patients and ascertain their serotypes and resistance.MethodsThe study was conducted in a closed population, involving all pediatricians and otolaryngologists in Sado Island allowing accurate determination of AOM incidence. In each month, one week was assigned as “surveillance week”, and all outpatients with acute illness aged 0–18 years examined during the surveillance weeks were enrolled. AOM was diagnosed on the basis of otoscopic findings and clinical symptoms were recorded. Specimens were collected from the nasopharynx or middle ear cavity of AOM patients and examined for bacteria. Antimicrobial susceptibilities, serotypes, and molecular typing for resistance were determined among Streptococcus pneumoniae and Haemophilus influenzae. ResultsIn total, 8,283 clinic visits were conducted, and 354 episodes (4.3%, 95% CI: 3.9–4.7%) among 312 children were diagnosed as AOM. The incidence of AOM was highest in children of 1 year of age (0.54 episodes/child/year, 95% CI: 0.44–0.64). Serotype coverage of 7- and 13-valent pneumococcal conjugate vaccines in this study were 38.0% (95% CI: 29.3–47.3) and 62.8% (95% CI: 53.6–71.4), respectively. Of 122 H.influenzae isolates available for typing, 120 were nontypeable and 2 were type b. A high proportion of S. pneumoniae isolates (46%) showed resistance to penicillin. Approximately half of H. influenzae isolates had genetic markers for beta-lactamase-negative ampicillin-resistance.ConclusionsApproximately 4–5% of pediatric outpatients, even without AOM-related symptoms, had AOM in our study. Pediatricians as well as otolaryngologists should check the tympanic membrane findings of all pediatric outpatients.

This study examined the differences between congenital cholesteatoma (CC) and acquired cholesteatomas (AC) in children by comparing clinical features and treatment courses. This was a retrospective study which retrospectively evaluated 127 children with middle ear cholesteatomas using medical records from January 1999 to December 2012 in the Department of Otolaryngology, Niigata University Hospital. The study comprised 69 and 58 cases of CC and AC, respectively. The main outcome measures include patient backgrounds, the opportunities for consultations, mastoid cell development, intraoperative finding of stapes, surgical procedure and number of surgeries. The average age at operation was 6.4 and 9.8 years in CC and AC, respectively. AC was more prevalent in boys. Mastoid development was better in CC than in AC. We adopted a two-stage operation in 17 cases (25 %) of CC and in 22 cases (38 %) of AC. The repeat surgery rate was 11.6 % in CC and 27.6 % in AC. Three times as many operations were required for three cases (4.3 %) of CC and 10 cases (17.2 %) of AC. The lesions in AC were more difficult to control. In the treatment of pediatric middle ear cholesteatoma, we had to keep the outcome in mind.

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The CTLA4-Ig therapeutics abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) co-stimulatory ligands. Both compounds preferentially bind CD80, yet CD86 has been implicated as the dominant co-stimulatory ligand. Using directed evolution methods, novel CTLA4-Ig variants were created with selective CD86 binding affinity, a property that confers increased immunosuppressive potency and potentially improved efficacy and safety profiles. Relative to abatacept (wild-type CTLA4-Ig), ASP2408 and ASP2409 have 83-fold and 220-fold enhanced binding affinity to CD86 while retaining 1.5-fold and 5.6-fold enhanced binding affinity to CD80, respectively. Improvements in CD86 binding affinity correlates with increased immunosuppressive potencyin vitroandin vivo Our results highlight the power of directed evolution methods to obtain non-intuitive protein engineering solutions and represent the first examples of CD86-selective CTLA4-Ig compounds that have entered clinical trials.

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