Vitamin C demand is increased after total knee arthroplasty: a double-blind placebo-controlled-randomized study.

PURPOSE: This study was designed to determine whether perioperative supplementation of vitamin C (VC) improves range of motion (ROM) and reduces the risk of arthrofibrosis (AF) following total knee arthroplasty (TKA). METHODS: Ninety-five patients undergoing TKA were randomized to either oral VC (1000 mg daily) or placebo for 50 days (48 VC group, 47 placebo group). The effect of VC supplementation was tested on ROM, AF, WOMAC, FJS-12, and VC plasma concentrations (VCc). VCc were analyzed in both patient groups before surgery, 4 and 7 days after surgery. RESULTS: ROM at 1 year was not different between study groups. The prevalence of AF was 5 of 48 (10.4%) in the VC group compared to 11 of 47 (23.4%) in the placebo group (p = 0.09). VCc decreased post-operatively in the placebo group (49-12 µmol/l on day 7, p < 0.001), but not in the VC group (53-57 µmol/l). Patients with a perioperative drop of VCc ≥ 30 µmol/l developed significantly more AF at 1 year compared to patients with a VCc drop of < 30 µmol/l (p = 0.007). CONCLUSIONS: TKA results in VC depletion. Perioperative VC supplementation prevents VCc drop in most patients undergoing TKA and may lower the incidence of AF. The clinical relevance of this study is that VC supplementation seems to be a cheap and safe adjunct to improve functional outcome after TKA. LEVEL OF EVIDENCE: I. TRIAL REGISTRY: The study was registered at the ISRCTN registry with study ID ISRCTN40250576.

Efficacy of hinged and carbon fiber ankle-foot orthoses in children with unilateral spastic cerebral palsy and drop-foot gait pattern.

BACKGROUND: In children with unilateral spastic cerebral palsy (USCP), ankle-foot orthoses (AFOs) are widely used to correct common gait deviations such as a drop-foot pattern. Most studies on this topic have investigated specific time points while omitting other parts of the gait cycle. OBJECTIVES: This study investigated the separate effects of prefabricated carbon fiber AFOs and custom-made hinged AFOs compared with barefoot walking in children with USCP with a drop-foot gait pattern using statistical parametric mapping. STUDY DESIGN: Retrospective, cross-sectional, repeated measures study. METHODS: Twenty ambulatory children (9.9 ± 2.5 years) with USCP and a drop-foot gait pattern were included. Kinematics, kinetics, and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking. Statistical parametric mapping was used to compare joint angles and moment waveforms. Kinematics, kinetics and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking for each AFO type but not between the 2 AFO types. RESULTS: Compared with barefoot walking, there was a steeper sole angle at initial contact, corresponding to a heel strike pattern, and an increased ankle dorsiflexion in swing with the use of both AFOs. The ankle plantar flexion moment during loading response increased. Ankle power generation during pre-swing decreased in the carbon fiber AFO group when walking with AFOs. CONCLUSIONS: Both AFOs were beneficial for improving a drop-foot gait pattern in these small patient groups and can, therefore, be recommended to treat this gait deviation in patients with unilateral cerebral palsy. However, the reduction in ankle power generation during push-off and additional goals targeted by AFOs, such as correction of structural or flexible foot deformities, should be considered for prescription.

Chronic Lateral Ankle Instability with Os Subfibulare in a Child Treated with Modified Broström/Gould Surgical Technique - A Case Report.

Introduction: Patients with lateral instability of the ankle have a much higher prevalence of an os subfibulare compared with the general population. In children and adolescents with known os subfibulare and chronic instability of the ankle, surgical resection of the os subfibulare and the Broström/Gould procedure to reattach the ATFL to the fibula has been described if conservative therapy fails. Case Report: Our case is about a 10-year-old girl with chronic instability of the ankle and a symptomatic os subfibulare, with additional cystic and edematous changes in the distal fibula in the MRI. Due to the reduced bone density, we assumed a higher risk of anchor pullout with the normal refixation at the distal fibula. Therefore, the surgical technique according to Broström/Gould was modified and the ATFL was refixed on the talar side. Conclusion: In cases of symptomatic os subfibulare with clinical instability of the ankle, a Broström/Gould operation and resection of the os subfibulare is recommended after failure of conservative therapy. Our case showed that a very satisfying post-operative result can be achieved with a modification of the Broström/Gould operation, with reattachment of the ATFL to the talus instead of the fibula.

Effects of ankle-foot orthoses on different gait patterns in children with spastic cerebral palsy: A statistical parametric mapping study.

BACKGROUND: Ankle-foot orthoses (AFOs) are a common treatment to correct gait deviations in children with spastic cerebral palsy (SCP). Studies on the outcome of AFOs on gait often do not account for different gait patterns. OBJECTIVES: The aim of this study was to investigate the effects of AFOs on specific gait patterns in children with cerebral palsy. STUDY DESIGN: Retrospective, unblinded, controlled, cross-over study. METHODS: Twenty-seven children with SCP were assessed in the conditions walking barefoot or with shoes and AFO. AFOs were prescribed based on usual clinical practice. Gait patterns for each leg were classified as excess ankle plantarflexion in stance (equinus), excess knee extension in stance (hyperextension), or excess knee flexion in stance (crouch). Differences in spatial-temporal variables and sagittal kinematics and kinetics of the hip, knee, and ankle between the 2 conditions were determined using paired t-tests and statistical parametric mapping, respectively. The effect of AFO-footwear neutral angle on knee flexion was tested using statistical parametric mapping regression. RESULTS: AFO use improved spatial-temporal variables and reduced ankle power generation in preswing. For "equinus" and "hyperextension" gait patterns, AFOs decreased ankle plantarflexion in preswing and initial swing and decreased ankle power in preswing. Ankle dorsiflexion moment increased in all gait pattern groups. Knee and hip variables did not change in any of the 3 groups. AFO-footwear neutral angle had no effect on changes in sagittal knee angle. CONCLUSION: Although improvements in spatial-temporal variables were seen, gait deviations could only partially be corrected. Therefore, AFO prescriptions and design should individually address specific gait deviations and their effectiveness in children with SCP should be controlled.

Does pathologically increased or decreased tibial torsion affect muscle activations during walking in typically developing adolescents?

A reduced capacity of plantar flexors and other muscles to extend the hip and knee during gait was shown in modelling studies when the tibial torsion angle is > 30° than normal. The aim of the current study was to determine if patients with increased or decreased tibial torsion show deviating muscle activations in knee and hip extensors in surface electromyography (EMG). Patients with CT confirmed increased tibial torsion (n = 19, ITT), decreased tibial torsion (n = 21, DTT) and age-matched healthy controls (n = 20) were included in this retrospective study. Additionally, kinematic and kinetic data were recorded during three-dimensional gait analysis. Surface EMG was recorded for vastus medialis and medial hamstrings. Statistical parametric mapping with a one-way ANOVA and post-hoc Bonferroni corrected two-sample t-tests were used to obtain differences in joint angles and moments. ITT and DTT showed an increased and decreased external foot progression angle, respectively. No additional muscle activations in vastus medialis and medial hamstrings were found in both patient groups compared to controls. DTT showed an increased hip flexion through parts of the gait cycle and both patient groups had a decreased knee extension moment in terminal stance. Our hypothesis of deviating muscle activation had to be rejected. It could be that in most orthopaedic patients the amount of exceeding tibial torsion is too low to cause substantial deviations in gait and muscle activation patterns.

Compensatory gait deviations in patients with increased outward tibial torsion pre and post tibial derotation osteotomy.

BACKGROUND: Tibial torsion describes the rotation between the proximal and distal joint axis along the shaft, which can be, as rotational deformity, pathologically increased or decreased. Some patients might increase hip internal rotation during walking to compensate increased outward tibial torsion. RESEARCH QUESTION: The aim of this study was to assess the effect of tibial derotation osteotomy on gait deviations in patients with increased outward tibial torsion. METHODS: Thirteen patients (13.5 ± 1.4 yrs, 22 limbs) with increased tibial torsion (CT confirmed 49.2 ± 4.8°) were analyzed pre and post tibial derotation osteotomy and compared with 17 typically developing children (TDC, 13.5 ± 2.3 yrs, 32 limbs). Kinematic and kinetic data were recorded. Subgroup analyses were performed whether patients showed compensatory hip internal rotation (Comp) or not (NoComp). Principal component (PC) analysis was used to achieve data transformation. A linear mixed model was used to estimate the main effect of PC-scores of retained PCs explaining 90% of the cumulative variance. RESULTS: Compensatory hip internal rotation (Comp, present in 45.5% of limbs analyzed) led to a lower external foot progression angle compared to patients without compensatory hip internal rotation (NoComp). In both patient groups foot progression angle was normalized after tibial derotation osteotomy. Post-operative NoComp had normalized frontal plane joint loadings, while Comp showed an increased hip and knee adduction moment. SIGNIFICANCE: Future studies should investigate if more time is needed for Comp to normalize gait patterns post-operative or if a pre and post-operative gait training might help. Otherwise the increased knee adduction moment might be clinically relevant due to previous studies reporting a possible association with knee osteoarthritis.

The impact of increased femoral antetorsion on gait deviations in healthy adolescents.

Increased femoral antetorsion leads to several gait deviations, and amongst others, an increased knee flexion was reported in mid and terminal stance. Therefore, the purpose of this retrospective study was to identify gait deviations caused by increased femoral antetorsion and to perform subgroup analyses based on sagittal knee kinematics. Patients with isolated, CT confirmed increased femoral antetorsion (n = 42) and age-matched typically developing children (TDC, n = 17) were included in this study. Patients were referred to gait analysis because of gait abnormalities going along with an increased femoral antetorsion ≥30°. Kinematic and kinetic data were recorded during 3D gait analysis and three valid gait cycles were analyzed. Principal component (PC) analysis was used to achieve data transformation. A linear mixed model was used to estimate the group effect of PC-scores of retained PCs explaining 90% of the cumulative variance. Group effects of PC-scores revealed that patients walked with more flexed hips and greater anterior pelvic tilt throughout the gait cycle. Knee flexion was increased in patients during mid and terminal stance. Increased frontal plane knee and hip joint moments were found for patients compared to TDC. Furthermore, dividing patients into two subgroups based on their sagittal knee kinematics showed that kinematic gait deviations were more pronounced in patients with higher femoral antetorsion, while deviations in joint moments were more pronounced in patients with lower femoral antetorsion. Increased femoral antetorsion showed alterations in all lower limb joints and may be not only a cosmetic problem. Therefore, 3D gait analysis should be used for clinical management and operative treatment should be considered depending on severity of gait deviations.

Retrospective Evaluation of Changes in Gait Patterns in Children and Adolescents With Cerebral Palsy After Multilevel Surgery.

The purpose of this study was to retrospectively investigate changes in gait patterns after single-event multilevel surgery in children and adolescents with bilateral cerebral palsy. Three-dimensional instrumented pre- and postoperative gait data of 12 patients were compared to data of 12 healthy control subjects using principal component analysis to reduce the dimensionality of kinematic and kinetic gait data and detect gait differences. The differences between pre- and postoperative data and between postoperative data and data of control subjects were calculated using a linear mixed model. The results revealed 14 significant effects for pre- and postoperative waveforms and 11 significant effects for postoperative and control waveforms. Patients after single-event multilevel surgery walked with smaller internal foot progression angle throughout the gait cycle, lower knee flexion at initial swing, and earlier knee extension during terminal swing. Retained gait deviations included excessive pelvic tilt and internally rotated and flexed hips over the entire gait cycle. Contrary to our hypothesis, postoperative waveforms in the sagittal plane differed more from control waveforms than from preoperative waveforms. These results emphasize the importance of carefully planning further conservative therapy 2 years after single-event multilevel surgery.

Homocysteine status and polymorphisms of methylenetetrahydrofolate reductase are not associated with restenosis after stenting in coronary arteries.

OBJECTIVE: We investigated the influence of elevated homocysteine plasma levels and 2 polymorphisms, 677C/T and 1298A/C, of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of restenosis after stenting in patients with symptomatic coronary artery disease. METHODS AND RESULTS: Homocysteine levels and MTHFR genotypes were determined in 800 consecutive patients treated with coronary artery stenting. Angiographic restenosis (> or =50% diameter stenosis at 6-month follow-up) was present in 25.8% of the patients with low homocysteine levels (at or below the median of 11.6 micromol/L; n=400) and 24.1% of the patients with high homocysteine levels (>11.6 micromol/L; n=400; P=0.62). Rates of angiographic restenosis were 26.0%, 23.5%, and 26.9% in carriers of the 677CC, 677CT, and 677TT genotypes (P=0.75), respectively, and 24.4%, 25.9%, and 24.0% in patients with the 1298AA, 1298AC, and 1298CC genotypes (P=0.90), respectively. The need for restenosis-driven reintervention (clinical restenosis) was 18.8% in subjects with low homocysteine concentrations and 19.0% in subjects with high homocysteine concentrations during the first year after the intervention (P=0.93). Rates of clinical restenosis were 19.5%, 17.1%, and 23.3% in carriers of the 677CC, 677CT, and 677TT genotypes (P=0.37), respectively, and 17.6%, 18.6%, and 24.7% in patients with the 1298AA, 1298AC, and 1298CC genotypes (P=0.27), respectively. CONCLUSIONS: Elevated levels of homocysteine and 2 polymorphisms of the MTHFR gene are not associated with restenosis after stenting in coronary arteries.

Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma.

Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy.