Recent National Institute for Health and Care Excellence (NICE) guidance has advised against the continued use of the
Introduction. Low back pain (LBP) is a worldwide leading cause of disability. This preclinical study evaluated the safety of a combined advanced therapy medicinal product developed during the European iPSpine project (#825925) consisting of mesendoderm progenitor cells (MEPC), derived from human induced pluripotent stem cells, in combination with a synthetic poly(N-isopropylacrylamide) hydrogel (NPgel) in an ovine intervertebral disc degeneration (IDD) model. Method. IDD was induced through nucleotomy in 4 adult sheep, 5 lumbar discs each (n=20). After 5 weeks, 3 alternating discs were treated with NPgel (n=6) or NPgel+MEPC (n=6). Before sacrifice, animals were subjected to: MRI of lumbar spines (disc height and Pfirmann grading); blood sampling (hematological, biochemical, metabolic and lymphocyte/monocytes immunological). After 3 months the sheep were sacrificed. The spines were processed for: macroscopic morphology (Thompson grading), microscopic morphology (Histological grading), and glycosaminoglycan content (GAG, DMMB Assay). Furthermore, at sacrifice biodistribution of human MEPC was assessed by Alu-sequences quantification (qPCR) from three tissue samples of heart, liver, spleen, brain, lungs, and kidneys, and PBMCs collected to assess activation of systemic immune cells. To each evaluation, appropriate statistical analysis was applied. Result. Flow cytometry showed no induction of systemic activation of T cells or monocytes. Alu quantification did not give detection of any cells in any organ. Disc height index was slightly increased in discs treated with NPgel+MEPC. Pfirmann's and
Abstract. Objectives. Up to 19% of patients who undergo surgery for an acute hip fracture are readmitted to the hospital within three months of the index operation. We aimed to identify risk factors for unplanned clinic attendance, readmission, and mortality within the first 12 months postoperatively and subsequently determine if there is a role for routine follow-up. Methods. Patients greater than 65 years old who underwent hip hemiarthroplasty using an uncemented
Reported rates of dislocation in hip hemiarthroplasty
(HA) for the treatment of intra-capsular fractures of the hip, range
between 1% and 10%. HA is frequently performed through a direct
lateral surgical approach. The aim of this study is to determine
the contribution of the anterior capsule to the stability of a cemented
HA through a direct lateral approach. . A total of five whole-body cadavers were thawed at room temperature,
providing ten hip joints for investigation. A
Background. Many factors contribute to the occurrence of edge-loading conditions in hip replacement; soft tissue tension, surgical position, patient biomechanical variations and type of activities, hip design, etc. The aim of this study was to determine the effect of different levels of rotational and translational surgical positioning of hip replacement bearings on the occurrence and severity of edge-loading and the resultant wear rates. Method. The Leeds II Hip-Joint Simulator and 36mm diameter alumina matrix composite ceramic bearings (BIOLOX delta, DePuy Synthes, UK) were used in this study. Different levels of mismatch between the reconstructed rotational centres of the head and the cup were considered (2, 3 and 4mm) in the medial-lateral axis. Two cup inclination angles were investigated; an equivalent to 45 and 65 degrees in-vivo, thus six conditions (n=6 for each condition) were studied in total with three million cycles completed for each condition. The wear of the ceramic-on-ceramic bearings were determined using a microbalance (Mettler Toledo, XP205, UK) and the dynamic microseparation displacement was measured using a Liner Variable Differential Transformer. Results. When a translational joint centre mismatch was coupled with a higher cup inclination angle, the severity of edge-loading increased when compared with the effect of those variables applied individually. Increasing the medial-lateral joint centre mismatch from 2 to 3 to 4mm resulted in increased wear rates under both cup inclination angles, with the 65 degree cup inclination angle having significantly higher wear rate than the cup inclination angle of 45 degree (p=0.02, p=0.02, and p<0.01 respectively). Conclusion. The cups with a 45 degree inclination angle showed greater resistance to dynamic microseparation as a result of joint centre mismatch. This study demonstrated that optimal position should not only consider the rotational position of the acetabular cup but also the relative centres of rotation of the head and the cup. Disclosure. John Fisher is a paid consultant to DePuy Synthes. Jonathan
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.Objectives
Methods
Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.