We hypothesised that a large acromial cover with an upwardly tilted glenoid fossa would be associated with degenerative rotator cuff tears (RCTs), and conversely, that a short acromion with an ...inferiorly inclined glenoid would be associated with glenohumeral osteoarthritis (OA). This hypothesis was tested using a new radiological parameter, the critical shoulder angle (CSA), which combines the measurements of inclination of the glenoid and the lateral extension of the acromion (the acromion index). The CSA was measured on standardised radiographs of three groups: 1) a control group of 94 asymptomatic shoulders with normal rotator cuffs and no OA; 2) a group of 102 shoulders with MRI-documented full-thickness RCTs without OA; and 3) a group of 102 shoulders with primary OA and no RCTs noted during total shoulder replacement. The mean CSA was 33.1° (26.8° to 38.6°) in the control group, 38.0° (29.5° to 43.5°) in the RCT group and 28.1° (18.6° to 35.8°) in the OA group. Of patients with a CSA > 35°, 84% were in the RCT group and of those with a CSA < 30°, 93% were in the OA group. We therefore concluded that primary glenohumeral OA is associated with significantly smaller degenerative RCTs with significantly larger CSAs than asymptomatic shoulders without these pathologies. These findings suggest that individual quantitative anatomy may imply biomechanics that are likely to induce specific types of degenerative joint disorders.
Magnetically controlled growing rods (MCGRs) allow non-invasive correction of the spinal deformity in the treatment of early-onset scoliosis. Conventional growing rod systems (CGRS) need repeated ...surgical distractions: these are associated with the effect of the 'law of diminishing returns'. The primary aim of this study was to quantify this effect in MCGRs over sequential distractions.
A total of 35 patients with a maximum follow-up of 57 months were included in the study. There were 17 boys and 18 girls with a mean age of 7.4 years (2 to 14). True Distraction (TD) was determined by measuring the expansion gap on fluoroscopy. This was compared with Intended Distraction (ID) and expressed as the 'T/I' ratio. The T/I ratio and the Cobb angle were calculated at several time points during follow-up.
The mean follow-up was 30 months (6 to 57). There was a significant decrease in the mean T/I ratio over time (convex rod at 3 months 0.81, sd 0.58
51 months 0.17, sd 0.16, p = 0.0001; concave rod at 3 months 0.93, sd 0.67
51 months 0.18, sd 0.15, p = 0.0001). A linear decline of the mean T/I ratios was noted for both convex rods (r
= 0.90, p = 0.004) and concave rods (r
= 0.81, p = 0.015) over 51 months. At the 24-month follow-up stage, there was a significant negative correlation between the mean T/I ratio of the concave rod with weight (r = -0.59, p = 0.01), age (r = -0.59, p = 0.01), and BMI of the child (r = -0.54, p = 0.01).
The 'law of diminishing returns' is also seen after serial distraction using MCGR. Compared to previously published data for CGRS, there is a gradual linear decline rather than a rapid initial decline in lengthening. In older, heavier children a reduced distraction ratio in the concave rod of the MCGR device is noted over time. Cite this article:
2017;99-B:1658-64.
Abstract The extracellular matrix (ECM) exerts powerful control over many cellular phenomena, including stem cell differentiation. As such, design and modulation of ECM analogs to ligate specific ...integrin is a promising approach to control cellular processes in vitro and in vivo for regenerative medicine strategies. Although fibronectin (FN), a crucial ECM protein in tissue development and repair, and its RGD peptide are widely used for cell adhesion, the promiscuity with which they engage integrins leads to difficulty in control of receptor-specific interactions. Recent simulations of force-mediated unfolding of FN domains and sequences analysis of human versus mouse FN suggest that the structural stability of the FN's central cell-binding domains (FN III9–10) affects its integrin specificity. Through production of FN III9–10 variants with variable stabilities, we obtained ligands that present different specificities for the integrin α5 β1 and that can be covalently linked into fibrin matrices. Here, we demonstrate the capacity of α5 β1 integrin-specific engagement to influence human mesenchymal stem cell (MSC) behavior in 2D and 3D environments. Our data indicate that α5 β1 has an important role in the control of MSC osteogenic differentiation. FN fragments with increased specificity for α5 β1 versus αv β3 results in significantly enhanced osteogenic differentiation of MSCs in 2D and in a clinically relevant 3D fibrin matrix system, although attachment/spreading and proliferation were comparable with that on full-length FN. This work shows how integrin-dependant cellular interactions with the ECM can be engineered to control stem cell fate, within a system appropriate for both 3D cell culture and tissue engineering.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BackgroundRecent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding ...whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results.MethodsWe retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle dʼAubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups.ResultsAt one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009).ConclusionsPatients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.Level of EvidenceTherapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.
Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained ...elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Objective Evaluation of the internal construct validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index adapted for use in patients with femoro-acetabular ...impingement (FAI) and osteoarthritis (OA) of the hip. Methods Distribution of a German version of WOMAC to patients upon first consultation. Patients with FAI n = 100, mean age 31.7 years, standard deviation (SD) 9.7 and OA ( n = 57, mean age 60.3 years, SD 11.7) and without comorbidities or prior hip surgery were included and compared to age- and gender-matched control population to FAI ( n = 200, mean age 32.6 years, SD 5.6). WOMAC data of 157 questionnaires were evaluated by Rasch analysis using RUMM2020 software. Results Summation of total WOMAC shows misfit to the Rasch model as well as multidimensionality. While the pain subset shows adequate fit and is unidimensional, item reduction is required to fit a unidimensional subset of functional items to the Rasch model. Summating the two fitting subsets yields again slight model misfit and multidimensionality requiring further item reduction. Finally, a 12-item version of the total WOMAC shows good model fit and unidimensionality, i.e., internal construct validity, for assessment of patients with FAI and OA without differential item functioning (DIF). A person separation index (PSI) = 0.93 indicates a high internal consistency reliability for the 12-item subscale. Scores for FAI are significantly higher than control ( P < 0.001, effect size 0.71) and lower than OA group ( P < 0.001, effect size 0.45). Adequate statistical power is shown discriminating the three groups, therefore indicating some evidence also for external construct validity. Conclusions The WOMAC as a total construct is multidimensional and summating the subsets into a total score is not valid. The reduced 12-item WOMAC is demonstrated to have internal construct validity for assessing patients with FAI and OA on the same scale and high internal consistency reliability. Discrimination of the groups with adequate statistical power also indicates external construct validity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the cost-effectiveness of dibotermin alfa compared with autologous iliac crest bone graft (ICBG) for patients undergoing single level lumbar interbody spinal fusion in a UK hospital ...setting.
An individual patient data (IPD) meta-analysis of six randomized controlled clinical trials and two single arm trials compared dibotermin alfa on an absorbable collagen implantation matrix (ACIM) (n = 456) and ICBG (n = 244) on resource use, re-operation rates, and SF-6D (Short form 6-dimension) health utility (total N = 700). Failure-related second surgery, operating time, post-operative hospital stay, and quality-adjusted life years (QALYs) derived from the IPD meta-analysis were included as inputs in an economic evaluation undertaken to assess the cost-effectiveness of dibotermin alfa/ACIM versus ICBG for patients undergoing single level lumbar interbody spinal fusion. A four year time horizon and the United Kingdom (UK) National Health Service (NHS) and Personal Social Services (PSS) perspective was adopted in the base case, with sensitivity analyses performed to gauge parameter uncertainty.
In the base case analysis, patients treated using dibotermin alfa/ACIM (12 mg pack) accrued 0.055 incremental QALYs at an incremental cost of £737, compared with patients treated with ICBG. This resulted in an incremental cost-effectiveness ratio (ICER) of £13,523, indicating that at a willingness-to-pay threshold of £20,000, dibotermin alfa/ACIM is a cost-effective intervention relative to ICBG from the NHS and PSS perspective.
In a UK hospital setting, dibotermin alfa/ACIM is a cost-effective substitute for ICBG for patients who require lumbar interbody arthrodesis.
Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented ...fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.
As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients.
Of the 90 patients screened, 77 passed the initial screening criteria. A total of 27 patients had a PI-LL mismatch and 23 had a dynamic spondylolisthesis. Following secondary inclusion and exclusion criteria, 31 patients were eligible for the study. Six patients were randomized and one underwent surgery during the study period. Given the low number of patients recruited and randomized, it was not possible to assess completion rates, quality of life, imaging, or health economic outcomes as intended.
This study provides a unique insight into the prevalence of dynamic spondylolisthesis and PI-LL mismatch in patients with symptomatic spinal stenosis, and demonstrates that there is a need for a definitive RCT which stratifies for these groups in order to inform surgical decision-making. Nonetheless a definitive study would need further refinement in design and implementation in order to be feasible.
Polymeric nanoparticle technology has evolved from drug carrier design to advanced multifunctional macromolecular structures. They enable drug delivery and release of a bioactive under ...spatio-temporal control rather than just passive release by a long-circulating carrier. As such, the carrier is enabling the biomolecule or the bioactive to carry out its designed biological function. Due to their small size nanoparticles may also induce perturbations of biological systems different from any other biomaterials, therefore opening up new biomedical applications as well as raising concerns about adverse effects.
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