Outcome of periacetabular osteotomy for the management of acetabular dysplasia: experience in an academic centre.

Periacetabular osteotomy (PAO) is a very effective reconstructive procedure for treatment of acetabular dysplasia. An orthopaedic paediatric surgeon and a reconstructive hip arthroplasty surgeon performed this procedure together in the early phase of their learning curve and then performed it individually. The early clinical and radiographic results of 85 consecutive PAOs performed in this academic orthopaedic unit were reviewed. The mean Merle-d\u27Aubigné score increased from 12.4 preoperatively to 16 at follow-up. Pre-operatively 73 hips were anteverted and 12 were neutral or retroverted. The mean angle of Wiberg improved from 5 degrees to 21 degrees (p \u3c 0.0001) in anteverted hips, and from 9 degrees to 30 degrees in neutral or retroverted hips. The mean angle of Lequesne and de Sèze improved from 6 degrees to 35 degrees (p \u3c 0.0001) in anteverted hips, and in neutral or retroverted hips from 9 degrees to 30 degrees (p \u3c 0.0001). The acetabular index improved from 26 degrees to 8 degrees (p \u3c 0.0001) in anteverted hips, and from 21 degrees to 7 degrees (p \u3c 0.0001) in neutral or retroverted hips. Over the 7 year period the blood loss and operative time improved from 2000 ml to 900 ml and 4 hours to 2 hours respectively. Four hips (four patients) required conversion to total hip replacement. The radiographic correction and improved clinical scores are similar to those in previous studies. This study shows a survival rate of 94% at 58 months following periacetabular osteotomy. The learning curve and the early results of this procedure performed in our academic unit are encouraging

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Review of Arthur E. Ellison's work on anterolateral rotatory laxity of the knee: The classic.

This classic discusses Arthur E. Ellison's (1926-2010) contributions to our understanding of anterolateral rotatory laxity of the knee. Ellison was a distinguished orthopaedic surgeon and one of the founding members of the American Orthopaedic Society for Sports Medicine (AOSSM). He served as the team physician for the United States ski team and Williamsburg football team. Ellison's publications focussed on the pathodynamics of knee stability, shedding light on the biomechanical functions of the iliotibial band. This led to the development of his lateral extra-articular procedure designed to control excessive tibial rotation in the anterior cruciate ligament (ACL) deficient knee. His work has made a significant contribution to our understanding of knee stability today, and many surgeons still use a modified version of Ellison's original technique to augment ACL reconstruction. This article summarises Ellison's original publications and the first description of his operative technique. The impact of his work is discussed in the context of modern practice. The aim of this study is to add these valuable insights to the current discussion regarding the optimal method for lateral extra-articular tenodesis. LEVEL OF EVIDENCE: V - Expert Opinion

Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation

<p>Abstract</p> <p>Background</p> <p>The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.</p> <p>Methods</p> <p>Primary human osteoblasts were exposed in vitro to 10^-8M dexamethasone over a 72 h time course. The phenotypic marker of osteoblast differentiation was analyzed was alkaline phosphatase activity. Intracellular β-catenin trafficking was assessed using immunoflourescence staining and TCF/LEF mediated transcription was analyzed using a Wnt luciferase reporter assay. Dkk1 expression was silenced using small interfering RNA (siRNA).</p> <p>Results</p> <p>Primary human osteoblasts exposed to dexamethasone displayed a significant reductions in alkaline phosphatase activity over a 72 h time course. Immunoflourescence analaysis of β-catenin localization demonstrated a significant reduction in intracytosolic and intranuclear β-catenin in response to dexamethasone exposure. These changes were associated with a reduction of TCF/LEF mediated transcription. Silencing Dkk1 expression in primary human osteoblasts exposed to dexamethasone resulted in an increase in alkaline phosphatase activity when compared to scrambled control.</p> <p>Conclusions</p> <p>Wnt/β-catenin signaling plays a key role in regulating glucocorticoid-induced osteoporosis <it>in vitro</it>. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. Targeting of the Wnt/β-catenin signaling pathway offers an exciting opportunity to develop novel anabolic bone agents to treat osteoporosis and disorders of bone mass.</p

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly