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Objective: To evaluate the safety and effectiveness of round window (RW), oval window (OW), CliP and Bell couplers for use with an active middle ear implant. Methods: This is a multicenter, long-term, prospective trial with consecutive enrollment, involving 6 university hospitals in Germany. Bone conduction, air conduction, implant-aided warble-tone thresholds and Freiburger monosyllable word recognition scores were compared with unaided preimplantation results in 28 moderate-to-profound hearing-impaired patients after 12 months of follow-up. All patients had previously undergone failed reconstruction surgeries (up to 5 or more). In a subset of patients, additional speech tests at 12 months postoperatively were used to compare the aided with the unaided condition after implantation with the processor switched off. An established quality-of-life questionnaire for hearing aids was used to determine patient satisfaction. Results: Postoperative bone conduction remained stable. Mean functional gain for all couplers was 37 dB HL (RW = 42 dB, OW = 35 dB, Bell = 38 dB, CliP = 27 dB). The mean postoperative Freiburger monosyllable score was 71% at 65 dB SPL. The postimplantation mean SRT<sub>50</sub> (speech reception in quiet for 50% understanding of words in sentences) improved on average by 23 dB over unaided testing and signal-to-noise ratios also improved in all patients. The International Outcome Inventory for Hearing Aids (IOI-HA)quality-of-life questionnaire was scored very positively by all patients. Conclusion: A significant improvement was seen with all couplers, and patients were satisfied with the device at 12 months postoperatively. These results demonstrate that an active implant is an advantage in achieving good hearing benefit in patients with prior failed reconstruction surgery.
The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.
Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS).
Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated.
Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.