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

Whole-exome sequencing in moyamoya patients of Northern-European origin identifies gene variants involved in Nitric Oxide metabolism: A pilot study

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular steno-occlusive disease of largely unknown etiology. Variants in the RNF213 gene are strongly associated with MMD in East-Asia. In MMD patients of Northern-European origin, no predominant susceptibility variants have been identified so far. Research question: Are there specific candidate genes associated with MMD of Northern-European origin, including the known RNF213 gene? Can we establish a hypothesis for MMD phenotype and associated genetic variants identified for further research? Material and methods: Adult patients of Northern-European origin, treated surgically for MMD at Oslo University Hospital between October 2018 to January 2019 were asked to participate. WES was performed, with subsequent bioinformatic analysis and variant filtering. The selected candidate genes were either previously reported in MMD or known to be involved in angiogenesis. The variant filtering was based on variant type, location, population frequency, and predicted impact on protein function. Results: Analysis of WES data revealed nine variants of interest in eight genes. Five of those encode proteins involved in nitric oxide (NO) metabolism: NOS3, NR4A3, ITGAV, GRB7 and AGXT2. In the AGXT2 gene, a de novo variant was detected, not previously described in MMD. None harboured the p.R4810K missense variant in the RNF213 gene known to be associated with MMD in East-Asian patients. Discussion and conclusion: Our findings suggest a role for NO regulation pathways in Northern-European MMD and introduce AGXT2 as a new susceptibility gene. This pilot study warrants replication in larger patient cohorts and further functional investigations

The effect of a pre- and postoperative orthogeriatric service on cognitive function in patients with hip fracture: randomized controlled trial (Oslo Orthogeriatric Trial)

BACKGROUND: Delirium is a common complication in patients with hip fractures and is associated with an increased risk of subsequent dementia. The aim of this trial was to evaluate the effect of a pre- and postoperative orthogeriatric service on the prevention of delirium and longer-term cognitive decline. METHODS: This was a single-center, prospective, randomized controlled trial in which patients with hip fracture were randomized to treatment in an acute geriatric ward or standard orthopedic ward. Inclusion and randomization took place in the Emergency Department at Oslo University hospital. The key intervention in the acute geriatric ward was Comprehensive Geriatric Assessment including daily interdisciplinary meetings. Primary outcome was cognitive function four months after surgery measured using a composite outcome incorporating the Clinical Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD). Secondary outcomes were pre- and postoperative delirium, delirium severity and duration, mortality and mobility (measured by the Short Physical Performance Battery (SPPB)). Patients were assessed four and twelve months after surgery by evaluators blind to allocation. RESULTS: A total of 329 patients were included. There was no significant difference in cognitive function four months after surgery between patients treated in the acute geriatric and the orthopedic wards (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P = 0.65). There was also no significant difference in delirium rates (49% versus 53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the intervention and the control group. In a pre-planned sub-group analysis, participants living in their own home at baseline who were randomized to orthogeriatric care had better mobility four months after surgery compared with patients randomized to the orthopedic ward, measured with SPPB (median 6 versus 4, 95% confidence interval for the median difference 0 to 2; P = 0.04). CONCLUSIONS: Pre- and postoperative orthogeriatric care given in an acute geriatric ward was not effective in reducing delirium or long-term cognitive impairment in patients with hip fracture. The intervention had, however, a positive effect on mobility in patients not admitted from nursing homes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01009268 Registered November 5, 2009

Eph/ephrin-B-mediated cell-to-cell interactions govern MTS20+ thymic epithelial cell development

Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B+) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20+ cells but fewer MTS20− cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell nteractions between either thymocytes–TECs or TECs–TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20+ TECs. This confirms, for the first time, that the presence of CD45+ cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20+ TECs

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

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