Retrospective study of cochlear implantations at a single facility focusing on postoperative complications

ObjectiveAlthough cochlear implantation (CI) is a relatively safe operation, postoperative complications sometimes occur. We reviewed the frequency and severity of complications of CI at our hospital. We compared our results with previously reported complications and considered measures to improve patient outcomes.MethodsThis retrospective study examined the medical records of 70 patients who received CI between March 2005 and December 2018. We collected the following data: age at the time of the first surgery, etiology of hearing impairment, date of implantation, type of implanted devices, and complications. Surgical complications were divided by time into perioperative, early, and late, and by severity into major or minor.ResultsRecords of 38 adults and 32 children were analyzed. Bilateral CI was performed in 16 patients, 8 of whom were sequential, and unilateral CI was performed in 54 patients. The total number of operations was 78 for 86 CI. Complications were observed in 15 of 78 operations (19%), and the rates of minor and major complications were 15% and 4%, respectively. Complication rates were 21% (8/39) for children and 10% (4/39) for adults. All of the perioperative and early complications were minor. There were three major complications, all of which were infections presenting with mastoiditis and subcutaneous or subperiosteal abscesses. One case required reimplantation twice because of recurrent mastoiditis and temporal abscess.ConclusionsThere was no significant difference in the incidence of complications between children and adults, but all major complications were infection in pediatric cases. Careful attention is needed to prevent postoperative infection.     

Minor contribution of CYP3A5 to the metabolism of hepatitis C protease inhibitor paritaprevir in vitro

1. Paritaprevir (PTV) is a non-structural protein 3/4A protease inhibitor developed for the treatment of hepatitis C disease as a fixed dose combination of ombitasvir (OBV) and ritonavir (RTV) with or without dasabuvir.

2. The aim of this study was to evaluate the effects of cytochrome P450 (CYP) 3A5 on in vitro PTV metabolism using human recombinant CYP3A4, CYP3A5 (rCYP3A4, rCYP3A5) and human liver microsomes (HLMs) genotyped as either CYP3A5*1/*1, CYP3A5*1/*3 or CYP3A5*3/*3.

3. The intrinsic clearance (CL_int, V_max/K_m) for the production of a metabolite from PTV in rCYP3A4 was 1.5 times higher than that in rCYP3A5. The PTV metabolism in CYP3A5*1/*1 and CYP3A5*1/*3 HLMs expressing CYP3A5 was comparable to that in CYP3A5*3/*3 HLMs, which lack CYP3A5.

4. CYP3A4 expression level was significantly correlated with PTV disappearance rate and metabolite formation. In contrast, there was no such correlation found for CYP3A5 expression level.

5. This study represents that the major CYP isoform involved in PTV metabolism is CYP3A4, with CYP3A5 having a minor role in PTV metabolism. The findings of the present study may provide foundational information on PTV metabolism, and may further support dosing practices in HCV-infected patients prescribed PTV-based therapy.