Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The role of the sterol sensing domain in HMG-CoA reductase regulation in Saccharomyces cerevisiae

Sterol sensing domain (SSD) containing proteins are required for lipid regulation, and are conserved among different organisms. 3-hydroxy-3-methyglutaryl-CoA reductase (HMGR) is a key enzyme for sterol synthesis that contains an SSD. In both mammals and yeast, HMGR undergoes regulated degradation in response to feedback of the mevalonate pathway. The configuration of HMGR changes when regulated by mevalonate molecules, which targets the protein for regulated degradation in the endoplasmic reticulum. The N-terminus of HMGR is necessary and sufficient for regulated degradation. The SSD of HMGR ranges from 5 out of 8 transmembrane spans of the N- terminus, and the SSD of HMGR is conserved between many organisms. In this work we investigated the role of the SSD in regulation of HMGR in Saccharomyces cerevisiae. We made 30 mutations in highly conserved residues of the SSD of budding yeast HMGR, and examined their phenotypes with respect to HMGR regulated degradation. To do this we used flow cytometry to measure HMGR levels in response to pharmacological manipulations of the mevalonate pathway that either increase or decrease degradation signals. We found that the SSD is involved in sensing FPP-derived molecule and oxysterol molecules. The SSD also contributed to the destabilization of HMGR during regulated degradation of the protei

The role of the sterol sensing domain in HMG-CoA reductase regulation in Saccharomyces cerevisiae

Sterol sensing domain (SSD) containing proteins are required for lipid regulation, and are conserved among different organisms. 3-hydroxy-3-methyglutaryl-CoA reductase (HMGR) is a key enzyme for sterol synthesis that contains an SSD. In both mammals and yeast, HMGR undergoes regulated degradation in response to feedback of the mevalonate pathway. The configuration of HMGR changes when regulated by mevalonate molecules, which targets the protein for regulated degradation in the endoplasmic reticulum. The N-terminus of HMGR is necessary and sufficient for regulated degradation. The SSD of HMGR ranges from 5 out of 8 transmembrane spans of the N- terminus, and the SSD of HMGR is conserved between many organisms. In this work we investigated the role of the SSD in regulation of HMGR in Saccharomyces cerevisiae. We made 30 mutations in highly conserved residues of the SSD of budding yeast HMGR, and examined their phenotypes with respect to HMGR regulated degradation. To do this we used flow cytometry to measure HMGR levels in response to pharmacological manipulations of the mevalonate pathway that either increase or decrease degradation signals. We found that the SSD is involved in sensing FPP-derived molecule and oxysterol molecules. The SSD also contributed to the destabilization of HMGR during regulated degradation of the protei

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar