Hearing preservation outcomes with different cochlear implant electrodes: Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422.

OBJECTIVES: In recent years, it has been possible to preserve hearing after cochlear implantation in patients with significant amounts of low-frequency residual hearing. Due to the dimensions and characteristics of the cochlear implants (CIs) Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422, both can be used to preserve residual hearing. The aim was to investigate the degree and progression of hearing preservation over a longitudinal postoperative period in a large consecutive cohort of implanted patients with preoperative residual hearing who received either the Nucleus Hybrid-L24 or the Nucleus Freedom CI422 implant. The intention was to examine potential characteristics and triggers of resulting postoperative hearing loss which may support a differentiation of CI candidacy criteria for a certain implant type. METHODS: A retrospective data analysis of patient files on consecutively implanted subjects presenting with a severe-to-profound sensorineural hearing loss at frequencies>1,500 Hz and substantial residual hearing at frequencies≤1,500 Hz, implanted with a Nucleus Hybrid-L24 (n=97) or a CI422 implant (n=100), was undertaken. A single-subject repeated-measure design comparing the mean threshold shift for pure-tone thresholds under headphones up to 24 months after implantation was used. RESULTS: Hearing preservation is observed in the majority of subjects with either implant (250-1,500 Hz frequency range). Hybrid-L24 patients exhibited a median hearing loss of 10 dB at initial fitting (n=97) and of 15 dB after 24 months (n=51). A 14.4-dB decrease in median hearing loss at initial fitting (n=100) and a 30-dB decrease after 24 months (n=28) was observed with the CI422 electrode. At initial fitting, 54.6% of the Hybrid-L24 (n=97) and 49.0% of the CI422 (n=100) subjects showed a mean threshold shift<15 dB. After 24 months, 58.8% (Hybrid-L24, n=51) and 28.6% (CI422, n=28) of the patients showed a mean threshold shift<15 dB. CONCLUSIONS: The results indicate that residual hearing was preserved for the majority of implanted patients with the Hybrid-L24 and the CI422 implant. Patients implanted with the Hybrid-L24 implant demonstrate greater stability and less median hearing loss over time than those with the CI422 implant. Assessments of onset and stability of hearing loss prior to implantation are important factors to consider during candidacy evaluation for electrode selection to potentially maximize the performance outcome for each patient.

Effects of dipeptidyl peptidase-4 inhibition in an animal model of experimental asthma: a matter of dose, route, and time.

The CD26-associated enzymatic activity of dipeptidyl peptidase-4 (DPP4) as well as the recruitment of CD26(+) T cells increase under allergic airway inflammation. Furthermore, genetic deficiency of CD26/DPP4 exerts protective effects in experimental asthma. Therefore, CD26/DPP4 might represent a novel therapeutic target in asthma. To study the effects of pharmacological inhibition of DPP4 on allergic airway inflammation the DPP4-inhibitor isoleucine thiazolidide was tested using different doses at different time points (at sensitization, immediately before and simultaneously with the allergen challenge, as well as continuously via drinking water), and different routes (intraperitoneal, oral, and by inhalation). Allergic-like airway inflammation was induced in Fischer 344 rats (Charles River) sensitized against ovalbumin (OVA) using OVA aerosols. Intraperitoneal application of the DPP4 inhibitor showed effects neither at sensitization nor at challenge, whereas a continuous application via drinking water using high doses of the inhibitor led to an aggravation of the histomorphological signs of airway inflammation. In contrast, aerosolization of the DPP4 inhibitor simultaneously with the allergen significantly reduced airway hyperresponsiveness and ameliorated histopathological signs compared to controls. In addition, this treatment resulted in increased mRNA levels of surfactant proteins, suggesting an involvement of DPP4 inhibitors in surfactant metabolism in OVA-challenged rats. Continuous systemic inhibition of DPP4 via the oral route aggravates allergic airway inflammation. In contrast, topical inhibition of DPP4 exerts potential protective effects, and further research in humans is needed.

Kinetics of regulatory T cells in the ovalbumin asthma model in the rat.

BACKGROUND: The kinetics of regulatory T cells (T(Reg)) in allergic diseases such as asthma are only partly known. METHODS: The asthma model in the Fischer rat with ovalbumin (OVA) sensitization and aerosol challenge was used. The relative and absolute numbers of leukocytes, lymphocytes and T(Reg) subsets were determined by flow cytometry in the lung interstitium and draining bronchial lymph nodes at different time points after two challenges, and lung function was tested in parallel. RESULTS: The progressive number of challenges resulted in increased relative and absolute numbers of lymphocytes and in particular of T(Reg). The T(Reg) number was augmented with each aerosol challenge and was already significantly increased 6 h after the second challenge. The relative (%) and absolute numbers of CD4+ and CD8+ T(Reg) and dendritic cells showed different kinetics after two challenges. The leukocyte numbers in the lung did not correlate with lung function. CONCLUSION: T(Reg) increased surprisingly early after challenge in the lung tissue. Relative and absolute numbers of leukocyte subsets should always be calculated. The kinetics of different leukocyte subsets can only be determined when several time points are studied.