Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

1. Download : Download high-res image (207KB)
2. Download : Download full-size image

     

Total Hip Arthroplasty in Ankylosing Spondylitis With Extension Contracture of Hips

Background

Despite significant pain relief following total hip arthroplasty (THA) in patients with ankylosing spondylitis, a small subset of patients presenting with extra-articular extension contracture of hips remains unsatisfied.

Anatomically contoured large femoral heads can reduce iliopsoas impingement: A cadaver verification study

While use of large heads in total hip arthroplasty (THA) continues to grow, concerns have been raised regarding anterior hip pain resulting from impingement of the prosthetic head against soft-tissues like the iliopsoas. To address these concerns, a new anatomically contoured head (ACH) was developed. In this study cadaver tests were utilized to show that iliopsoas impingement/tenting caused by conventional heads is significantly relieved with the more rounded and reduced distal profile of the ACH. Thus, the ACH implant may be able to decrease the risk of soft-tissue impingement with conventional heads, particularly in the smaller hip.     

Accuracy and Precision of Acetabular Component Placement With Imageless Navigation in Obese Patients

Background

Obesity is a risk factor for acetabular component malposition when total hip arthroplasty is performed with manual techniques. The utility of imageless navigation in obese patients remains unknown. This study compared the accuracy and precision of imageless navigation for component orientation between obese and nonobese patients.

不同手术方法治疗复杂胫骨平台骨折临床疗效观察

目的探讨不同手术方法治疗复杂胫骨平台骨折临床疗效。方法选择2016年1月—2018年12月84例复杂胫骨平台骨折患者,随机分组。单侧锁定钢板内固定组选择单侧锁定钢板内固定手术,双侧切口双侧解剖钢板内固定组选择双侧切口双侧解剖钢板内固定。分析手术操作时间、手术失血、平均住院天数以及复杂胫骨平台骨折愈合时间;治疗前后患者视觉模拟评分和Rasmussen膝关节功能评分;膝关节僵硬发生率。结果双侧切口双侧解剖钢板内固定组视觉模拟评分和Rasmussen膝关节功能评分、手术操作时间、手术失血、平均住院天数以及复杂胫骨平台骨折愈合时间、膝关节僵硬发生率和单侧锁定钢板内固定组比较有优势,P<0.05。结论复杂胫骨平台骨折患者实施双侧切口双侧解剖钢板内固定可获得较好效果。