Lumbar spinal fusion with β-TCP granules and variable Escherichia coli–derived rhBMP-2 dose

Background contextThe ideal tissue-engineered solution for any bone graft substitute is to assist in the rapid formation of bone and facilitate fusion.PurposeThe present study aims to evaluate this E-BMP-2 (Escherichia coli–derived human bone morphogenetic protein-2) in ovine posterolateral lumbar fusion (PLF) to examine the influence of dose and overall performance in a model with similar graft size and diffusive challenges to the human.Study design/settingIn vivo large animal model study.MethodsAn adult ovine PLF was performed in 30 animals with groups of E-BMP-2 with a beta-tricalcium phosphate (β-TCP) carrier at three different dosages, β-TCP alone, and autograft from the iliac crest. The fusions were assessed by radiography (X-ray and microcomputed tomography), mechanical testing, and hard-tissue histology with bone labels at 6, 8, and 10 weeks along with routine paraffin histology at 12 weeks.ResultsResults showed increasing new bone and fusion rate with E-BMP-2 dose, whereas β-TCP alone was largely resorbed and did not achieve fusion in this model at 12 weeks. Autograft showed similar grading for the amount of bone between the transverse processes but a lower fusion rate than β-TCP/E-BMP-2 groups. Bone labels revealed new bone formation at all time points for the E-BMP2 groups, whereas the autograft group showed active bone formation at 10 weeks. Beta-tricalcium phosphate displayed reliable incorporation into the decorticated host bone, whereas limited new bone was found between the transverse processes. At the center of the fusion mass, increased E-BMP-2 dose led to increased incorporation of β-TCP by new bone.ConclusionsThese results suggest that E-BMP-2 was capable of producing posterolateral fusion in the ovine model that is equal to or superior to autologous graft in terms of fusion rate and mechanical strength. E-BMP-2 dose had considerable influence on β-TCP granule resorption.     

Omitting pre-operative coagulation screening tests in hip fracture patients: Stopping the financial cascade?

BackgroundCoagulation screening continues as a standard of care in many hip fracture pathways despite the 2011 guidelines from the Association of Anaesthetists of Great Britain and Ireland (AAGBI) which recommend that such screening be performed only if clinically indicated. This study aims to evaluate the use of pre-operative coagulation screening and explore its financial impact.MethodsProspective data was collected in accordance with the “Standardised Audit of Hip Fractures in Europe” (SAHFE) protocol. All patients admitted to our hospital with hip fractures during a 12-month period from November 2011 to November 2012 were analysed. Data including coagulation results and the use of vitamin K or blood products were collected retrospectively from the hospital computer system. Patient subgroup analysis was performed for intraoperative blood loss, post-operative blood units transfused, haematoma formation and gastrointestinal haemorrhage.Results814 hip fractures were analysed. 91.4% (n = 744) had coagulation tests performed and 22.0% (n = 164) had an abnormal result. Of these, 55 patients were taking warfarin leaving 109 patients who had abnormal results and were not taking warfarin. When this group (n = 109) was compared to those who had normal test results (n = 580) and to all other patients (n = 705) there was no difference in intraoperative blood loss (p = 0.79, 0.78), postoperative transfusion (p = 0.38, 0.30), postoperative haematoma formation (p = 0.79, 1.00), or gastrointestinal haemorrhage (p = 0.45, 1.00), respectively. In those who were not taking warfarin, but had abnormal results, none had treatment to reverse their coagulopathy with either vitamin K or blood products. By omitting pre-operative coagulation tests in patients who are not taking warfarin, we estimate a financial saving of between £66,500 and £432,250 per annum.ConclusionsThis study supports the hypothesis that routine pre-operative coagulation screening is unnecessary in hip fracture patients unless they take warfarin or have a known coagulopathy. Moreover, its omission represents significant cost-saving potential.     

Exploratory analysis of cold,heat, deficiency,or excess pattern distribution in women with dysmenorrhea

ObjectiveTo understand the impact and implications of cold, heat, deficiency, or excess pattern identification in relation to dysmenorrhea, comparing the prevalence of these patterns between women with and without dysmenorrhea is needed.MethodsWe gathered data from the Korea Constitutional Multicenter Bank. A total of 508 patients were recruited and provided with cold, heat, deficiency, or excess pattern and dysmenorrhea questionnaires. On the basis of their responses, they were divided into the dysmenorrhea group (moderate or severe dysmenorrheic pain; n = 90) and non-dysmenorrhea group (no dysmenorrheic pain; n = 155). We analyzed the characteristics of the groups and compared the cold, heat, deficiency, or excess pattern scores. Comparisons were performed using the independent t-test. We also performed multiple comparisons of each individual symptom between the groups to explore which symptoms appear with dysmenorrhea using the Bonferroni adjustment method.ResultsThere was a high positive correlation between deficiency pattern scores and excess pattern scores (p < 0.001). The cold, deficiency, and excess pattern scores were significantly higher in the dysmenorrhea group than in the non-dysmenorrhea group (p < 0.001). Twenty among the 76 pattern items showed significant differences between the groups (p < 0.001). Among all items, there was a large effect size only in sleep quality (mean difference 1.07, 95% confidence interval 0.75–1.39, p < 0.001).ConclusionsWomen with dysmenorrhea have higher cold, deficiency, and excess pattern scores than those without dysmenorrhea. The longitudinal observation of these symptoms needs to be evaluated using a clinical prospective study design in accordance with pattern differentiation in the future.     

Porous membrane with reverse gradients of PDGF-BB and BMP-2 for tendon-to-bone repair: In vitro evaluation on adipose-derived stem cell differentiation

Polycaprolactone (PCL)/Pluronic F127 membrane with reverse gradients of dual platelet-derived growth factor-β (PDGF-BB) and bone morphogenetic protein 2 (BMP-2) concentrations was fabricated using a diffusion method to investigate the effect of reverse gradients of dual growth factor concentrations on adipose-derived stem cell (ASC) differentiations, such as tenogenesis and osteogenesis. The PDGF-BB and BMP-2 were continuously released from the membrane for up to 35 days, with reversely increasing/decreasing growth factors along the membrane length. Human ASCs were seeded on the membrane with reverse PDGF-BB and BMP-2 gradients. The cells were confluent after 1 week of culture, regardless of growth factor types or concentrations on the membrane. Gene expression (real-time polymerase chain reaction), Western blot and immunohistological analyses after 1 and 2 weeks of ASC culture showed that the membrane sections with higher PDGF-BB and lower BMP-2 concentrations provided a better environment for ASC tenogenesis, while the membrane sections with higher BMP-2 and lower PDGF-BB concentrations were better for promoting osteogenesis. The results suggest that the membrane with reverse gradients of PDGF-BB and BMP-2 may be promising for tendon-to-bone repair, as most essential biological processes are mediated by gradients of biological molecules in the body.     

Proportion of deproteinized bovine bone and autogenous bone affects bone formation in the treatment of calvarial defects in rabbits

This study assessed new bone formation generated using three different proportions of autogenous bone (AB) and deproteinized bovine bone (DBB). Thirty bicortical skull defects were prepared in 15 rabbits, divided into 3 groups: Group 1, critical size defect (CSD) versus AB as controls; Group 2, DBB versus a composite of AB and DBB using a proportion of 1:1; and Group 3, a composite of AB and DBB using a proportion of 1:2 versus a proportion of 1:4. After 8 weeks, radiographic evaluation was assessed using densitometry and new bone formation by histomorphometry. The mean optical density of the CSD (0.108 ± 0.238) and AB (0.352 ± 0.161) groups differed significantly from the DBB group (1.044 ± 0.093) and the groups using a proportion of 1:1 (0.905 ± 0.078), 1:2 (0.865 ± 0.294) and 1:4 (0.867 ± 0.304). Histomorphometry revealed a higher percentage of new bone in the AB group (30.223 ± 16.722) than in the groups using proportions of 1:2 (22.639 ± 5.659), 1:1 (20.929 ± 6.169), 1:4 (9.621 ± 2.400), DBB (14.441 ± 2.742) and CSD (10.645 ± 8.868), respectively. The 1:2 group had significantly higher bone content than the 1:4 group. The proportions of 1:1 and 1:2 resulted in greater bone formation than the proportion of 1:4, DBB and CSD.     

Dependency of disc degeneration on shear and tensile strains between annular fiber layers for complex loads

BackgroundOne of the first signs of disc degeneration is the formation of circumferential tears within the annulus fibrosus. It is assumed that high shear and tensile strains between the lamellae mainly cause the initiation of these failures. However, it is not known which load application and which degree of disc degeneration could lead to the highest strains and therefore, might induce the formation of tears. Therefore, the aim of this finite element (FE) study was, to find load combinations that would yield highest shear and tensile strains in differently degenerated discs.Materials and methodsA three-dimensional FE-model of a motion segment L4-5 was utilized in different degrees of disc degeneration (healthy, mild, moderate, and severe). The degenerated models consider the reduction of disc height, endplate curvatures, the osteophyte formation, the increase of nucleus compressibility, and the decrease of fiber and ligament stiffness. An axial compression load of 500 N together with moments of 7.5 Nm in single and combined load directions were simulated.ResultsHigh strains for the healthy and degenerated discs were predicted for load combinations, particularly for the combination of lateral bending plus flexion or extension. The maximum strains were located in the postero-lateral region of the disc. In comparison to the healthy disc, the maximum strains increased slightly for the mildly and moderately degenerated disc. Strains decreased strongly for the severely degenerated disc. With progressive degeneration, the size of the region of maximum strains diminished and the location transferred from the inner annulus to the adjacent bony endplates.ConclusionsThe results could be a possible explanation for the initiation of circumferential tears. The mildly degenerated disc model, which represents early stages of life, suggests that circumferential tears could primarily occur at these stages, especially for the load combinations of lateral bending plus axial rotation and lateral bending plus flexion.     

Surgical instrumentation for the in vivo determination of human lumbar spinal segment stiffness and viscoelasticity

The definition of spinal instability is still controversial. For this reason, it is essential to better understand the difference in biomechanical behaviour between healthy and degenerated human spinal segments in vivo. A novel computer-assisted instrument was developed with the objective to characterize the biomechanical parameters of the spinal segment. Investigation of the viscoelastic properties as well as the dynamic spinal stiffness was performed during a minimally invasive procedure (microdiscectomy) on five patients. Measurements were performed intraoperatively and the protocol consisted of a dynamic part, where spinal stiffness was computed, and a static part, where force relaxation of the segment under constant elongation was studied. The repeatability of the measurement procedure was demonstrated with five replicated tests. The spinal segment tissues were found to have viscoelastic properties. Preliminary tests confirmed a decrease in stiffness after decompression surgery. Patients with non-relaxed muscles showed higher stiffness and relaxation rate compared to patients with relaxed muscles, which can be explained by the contraction and relaxation reflex of muscles under fast and then static elongation. The results show the usefulness of the biomechanical characterization of the human lumbar spinal segment to improve the understanding of the contribution of individual anatomical structures to spinal stability.