Cohesin complex-associated holoprosencephaly

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly

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

Knee rotation during a weightbearing activity: influence of turning

Kinematic studies, in which mobile- and fixed-bearing total knee arthroplasty (TKA) were compared, showed controversial results with respect to axial femorotibial rotation. However, all studies focused only on straight ahead tasks, which may underestimate possible differences in freedom of rotation. The purpose of this study was to investigate the influence of turning on normal axial knee rotation. If large differences across tasks were to be found, this would support the use of this task in the evaluation of in-vivo TKA kinematics. In 15 healthy persons, crossover and sidestep turns were added to a standardized chair rise. Three-dimensional knee angles were recorded using an optoelectronic motion analysis system, and a noninvasive epicondylar frame was developed to track the femur. Compared to knee rotation during the straight ahead task, average peak tibial internal rotation increased during a crossover turn ( p < 0.001), as did peak external tibia rotation during a sidestep turn ( p < 0.001). The combined range of axial rotation for both turning tasks together was 20.9°, versus 13.5° for the straight ahead task ( p < 0.001). The turning maneuvers in this study induced a large range of axial knee rotation, so they could be important in studies comparing freedom of rotation in mobile- and fixed-bearing TKA. © 2008 Elsevier B.V. All rights reserved

The Femoral Epicondylar Frame to track femoral rotation in optoelectronic gait analysis

Relative movement of skin markers to underlying bone limits a valid interpretation of axial femorotibial rotation in noninvasive optoelectronic gait analysis. A distal femoral clamp is a practical solution for thigh marker placement, however, existing devices are still susceptible to measurement errors at increased angles of knee flexion. We developed the Femoral Epicondylar Frame (FEF), which should result in less femoral rotational measurement error due to its anatomic fitting and controlled pressure adjustment. Seven subjects with a total knee replacement in situ, mean age 71 years, mean body mass index 28, were equipped with the frame mounted with a set of tantalum markers. Fluoroscopic data was collected during a step-up motion. A three-dimensional model fitting technique was used to compare the in vivo position and orientation of the frame and the femoral prosthesis component of the prosthesis. The frame rotational measurement error appeared to be linearly dependent on the knee flexion angle. When considering knee flexion angles lower than 40° of flexion, the highest measurement error was 3.3° on average, with an absolute extreme of 6.2° It is concluded that the accuracy of the FEF is sufficient to evaluate axial knee rotation with optoelectronic gait analysis at group level in clinical studies. © 2010 Elsevier B.V

Mobile-bearing total knee arthroplasty: More rotation is evident during more demanding tasks

Background: Some reports showed few but significant more axial femorotibial rotation in favor of mobile-bearing (MB) versus fixed-bearing (FB) total knee arthroplasty (TKA), mostly during knee bend fluoroscopic studies. The goal of the current study was to submit MB and FB groups of TKA patients to a turning activity, in which additional rotation was to be expected. Methods: Two consecutive cohorts of patients after TKA (10 FB and 11 MB knees in a total of 18 patients) were assessed using motion analysis five year postoperatively, while performing gait and sit-to-walk (STW) movements with and without turning steps. Results: Mean range of rotation in the FB group increased from 9.7° during gait, to 11.7° during STW straight, and to 14.3° during STW turning. Mean range of rotation in the MB group increased from 13.4° during gait to 21.0° during STW straight, and stayed at 21.1° during STW turning. Conclusions: Too many uncontrolled variables in the current study hinder a meaningful discrimination of MB from FB TKA rotation. However, the study does illustrate how more demanding task loads could be helpful in exploring the geometric constraints of TKA variants. Level of Evidence: Level III, therapeutic study

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

Item does not contain fulltex

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