Anacetrapib lowers LDL by increasing ApoB clearance in mildly hypercholesterolemic subjects

BACKGROUND. Individuals treated with the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib exhibit a reduction in both LDL cholesterol and apolipoprotein B (ApoB) in response to monotherapy or combination therapy with a statin. It is not clear how anacetrapib exerts these effects; therefore, the goal of this study was to determine the kinetic mechanism responsible for the reduction in LDL and ApoB in response to anacetrapib.METHODS. We performed a trial of the effects of anacetrapib on ApoB kinetics. Mildly hypercholesterolemic subjects were randomized to background treatment of either placebo (n = 10) or 20 mg atorvastatin (ATV) (n = 29) for 4 weeks. All subjects then added 100 mg anacetrapib to background treatment for 8 weeks. Following each study period, subjects underwent a metabolic study to determine the LDL-ApoB-100 and proprotein convertase subtilisin/kexin type 9 (PCSK9) production rate (PR) and fractional catabolic rate (FCR).RESULTS. Anacetrapib markedly reduced the LDL-ApoB-100 pool size (PS) in both the placebo and ATV groups. These changes in PS resulted from substantial increases in LDL-ApoB-100 FCRs in both groups. Anacetrapib had no effect on LDL-ApoB-100 PRs in either treatment group. Moreover, there were no changes in the PCSK9 PS, FCR, or PR in either group. Anacetrapib treatment was associated with considerable increases in the LDL triglyceride/cholesterol ratio and LDL size by NMR.CONCLUSION. These data indicate that anacetrapib, given alone or in combination with a statin, reduces LDL-ApoB-100 levels by increasing the rate of ApoB-100 fractional clearance.TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00990808","term_id":"NCT00990808"}}NCT00990808.FUNDING. Merck & Co. Inc., Kenilworth, New Jersey, USA. Additional support for instrumentation was obtained from the National Center for Advancing Translational Sciences (UL1TR000003 and UL1TR000040).     

Orbital Fracture in a Professional Diver: Issues and Management

Background

We present a case report of a professional diver who sustained a fracture of the left orbital medial wall as well as floor exceeding 50% with orbital fat herniation blocking the maxillary sinus ostium. This may result in a closed cavity within the maxillary sinus that could potentially result in barotraumas during future diving. The aim of his surgery consists of repairing the orbital fracture and to aerating the sinus at the same sitting.

Method

A transconjunctival approach was used combined with endoscopic sinus surgery approach to the maxillary sinus. The orbital floor fracture was repaired with a titanium plate. A wide middle meatal antrostomy was performed. A size eight Foley’s catheter was inserted into the maxillary sinus and the balloon inflated to elevate and support the displaced inferior orbital floor bone fragment. The balloon was left in situ for 4 weeks to support the mobile inferior orbital fragment till adequate bone healing and stability.

Results

Patient recovered well. At 3 months post-operatively, the maxillary antrostomy remained patent, and a hyperbaric oxygen challenge test was performed with success. A repeat orbital CT scan 1 day after hyperbaric challenge showed no signs of air leakage, and the bony inferior orbital floor fracture has healed completely with the titanium plate in situ.

Conclusion

This is the first case report of repair of orbital floor fracture with simultaneous aeration of the maxillary sinus in a professional diver using a combined approach. The patient was able to resume his occupation as a professional diver following surgery.

     

Enhanced recovery following liver surgery: a systematic review and meta-analysis

Background

Enhanced recovery after surgery (ERAS) programmes aim to improve postoperative outcomes. They are being utilized increasingly in hepatic surgery. This review aims to evaluate the impact of ERAS programmes on outcomes following liver surgery.

Methods

EMBASE, MEDLINE, PubMed and the Cochrane Database were searched for trials comparing outcomes in patients undergoing liver surgery utilizing ERAS principles with those in patients receiving conventional care. The primary outcome was occurrence of postoperative complications within 30 days. Secondary outcomes included length of stay (LoS), functional recovery and adherence to ERAS protocols.

Results

Nine articles were included in the review, of which two were randomized controlled trials (RCTs). Overall complication rates were 25.0% (range: 11.5–46.4%) in ERAS patients, and 31.0% (range: 11.8–46.2%) in conventional care patients. Significantly reduced overall complication rates following ERAS care were demonstrated by a meta-analysis of the data reported in the two RCTs (odds ratio: 0.49, 95% confidence interval 0.28–0.84; P = 0.01) The median LoS reported by the studies was 5.0 days (range: 2.5–7.0 days) in ERAS patients, and 7.5 days (range: 3.0–11.0 days) in non-ERAS patients. Recovery milestones, when reported, were improved following ERAS care.

Conclusions

The adoption of ERAS protocols improves morbidity and LoS following liver surgery. Future ERAS programmes should accommodate the unique requirements of liver surgery in order to optimize postoperative outcomes.