The interaction between muscle pathophysiology, body mass, walking speed and ankle foot orthosis stiffness on walking energy cost: a predictive simulation study.

BACKGROUND: The stiffness of a dorsal leaf AFO that minimizes walking energy cost in people with plantarflexor weakness varies between individuals. Using predictive simulations, we studied the effects of plantarflexor weakness, passive plantarflexor stiffness, body mass, and walking speed on the optimal AFO stiffness for energy cost reduction. METHODS: We employed a planar, nine degrees-of-freedom musculoskeletal model, in which for validation maximal strength of the plantar flexors was reduced by 80%. Walking simulations, driven by minimizing a comprehensive cost function of which energy cost was the main contributor, were generated using a reflex-based controller. Simulations of walking without and with an AFO with stiffnesses between 0.9 and 8.7 Nm/degree were generated. After validation against experimental data of 11 people with plantarflexor weakness using the Root-mean-square error (RMSE), we systematically changed plantarflexor weakness (range 40-90% weakness), passive plantarflexor stiffness (range: 20-200% of normal), body mass (+ 30%) and walking speed (range: 0.8-1.2 m/s) in our baseline model to evaluate their effect on the optimal AFO stiffness for energy cost minimization. RESULTS: Our simulations had a RMSE < 2 for all lower limb joint kinetics and kinematics except the knee and hip power for walking without AFO. When systematically varying model parameters, more severe plantarflexor weakness, lower passive plantarflexor stiffness, higher body mass and walking speed increased the optimal AFO stiffness for energy cost minimization, with the largest effects for severity of plantarflexor weakness. CONCLUSIONS: Our forward simulations demonstrate that in individuals with bilateral plantarflexor the necessary AFO stiffness for walking energy cost minimization is largely affected by severity of plantarflexor weakness, while variation in walking speed, passive muscle stiffness and body mass influence the optimal stiffness to a lesser extent. That gait deviations without AFO are overestimated may have exaggerated the required support of the AFO to minimize walking energy cost. Future research should focus on improving predictive simulations in order to implement personalized predictions in usual care. Trial Registration Nederlands Trial Register 5170. Registration date: May 7th 2015.  http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5170.

Interacting effects of AFO stiffness, neutral angle and footplate stiffness on gait in case of plantarflexor weakness: A predictive simulation study.

To maximize effects of dorsal leaf ankle foot orthoses (AFOs) on gait in people with bilateral plantarflexor weakness, the AFO properties should be matched to the individual. However, how AFO properties interact regarding their effect on gait function is unknown. We studied the interaction of AFO bending stiffness with neutral angle and footplate stiffness on the effect of bending stiffness on walking energy cost, gait kinematics and kinetics in people with plantarflexor weakness by employing predictive simulations. Our simulation framework consisted of a planar 11 degrees of freedom model, containing 11 muscles activated by a reflex-based neuromuscular controller. The controller was optimized by a comprehensive cost function, predominantly minimizing walking energy cost. The AFO bending and footplate stiffness were modelled as torsional springs around the ankle and metatarsal joint. The neutral angle of the AFO was defined as the angle in the sagittal plane at which the moment of the ankle torsional spring was zero. Simulations without AFO and with AFO for 9 bending stiffnesses (0-14 Nm/degree), 3 neutral angles (0-3-6 degrees dorsiflexion) and 3 footplate stiffnesses (0-0.5-2.0 Nm/degree) were performed. When changing neutral angle towards dorsiflexion, a higher AFO bending stiffness minimized energy cost of walking and normalized joint kinematics and kinetics. Footplate stiffness mainly affected MTP joint kinematics and kinetics, while no systematic and only marginal effects on energy cost were found. In conclusion, the interaction of the AFO bending stiffness and neutral angle in bilateral plantarflexor weakness, suggests that these should both be considered together when matching AFO properties to the individual patient.

Total knee arthroplasty improves gait adaptability in osteoarthritis patients; a pilot study.

Background: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients' physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm).Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA.

Osteoarthritis year in review 2021: mechanics.

Osteoarthritis (OA) has a complex, heterogeneous and only partly understood etiology. There is a definite role of joint cartilage pathomechanics in originating and progressing of the disease. Although it is still not identified precisely enough to design or select targeted treatments, the progress of this year's research demonstrates that this goal became much closer. On multiple scales - tissue, joint and whole body - an increasing number of studies were done, with impressive results. (1) Technology based instrument innovations, especially when combined with machine learning models, have broadened the applicability of biomechanics. (2) Combinations with imaging make biomechanics much more precise & personalized. (3) The combination of Musculoskeletal & Finite Element Models yield valid personalized cartilage loads. (4) Mechanical outcomes are becoming increasingly meaningful to inform and evaluate treatments, including predictive power from biomechanical models. Since most recent advancements in the field of biomechanics in OA are at the level of a proof op principle, future research should not only continue on this successful path of innovation, but also aim to develop clinical workflows that would facilitate including precision biomechanics in large scale studies. Eventually this will yield clinical tools for decision making and a rationale for new therapies in OA.

Energy cost optimized dorsal leaf ankle-foot-orthoses reduce impact forces on the contralateral leg in people with unilateral plantar flexor weakness.

BACKGROUND: In individuals with unilateral plantar flexor weakness, the second peak of the vertical ground reaction force (GRF) is decreased. This leads to a higher ground reaction force, e.g. impact, of the contralateral leg, potentially explaining quadriceps muscle and/or knee joint pain. Energy cost optimized dorsal leaf ankle-foot-orthoses (AFOs) may increase the push-off ground reaction force, which in turn could lead to lower impact forces on the contralateral leg. RESEARCH QUESTIONS: 1) Are impact forces increased in the contralateral leg of people with unilateral plantar flexor weakness compared to healthy subjects? 2) Do energy cost optimized AFOs reduce impact forces and improve leg impact symmetry compared to walking without AFO in people with unilateral plantar flexor weakness? METHODS: Nine subjects with unilateral plantar flexor weakness were provided a dorsal leaf AFO with a stiffness primarily optimized for energy cost. Using 3D gait analyses peak vertical GRF during loading response with and without AFO, and the symmetry between the legs in peak GRF were calculated. Peak GRF and symmetry were compared with reference data of 23 healthy subjects. RESULTS: The contralateral leg showed a significant higher peak vertical GRF (12.0 ± 0.9 vs 11.2 ± 0.6 N/kg, p = 0.005) compared to healthy reference data. When walking with AFO, the peak vertical GRF of the contralateral leg significantly reduced (from 12.0 ± 0.9 to 11.4 ± 0.7 N/kg, p = 0.017) and symmetry improved compared to no AFO (from 0.93 ± 0.06 to 1.01 ± 0.05, p < 0.001). CONCLUSION: In subjects with unilateral plantar flexor weakness, impact force on the contralateral leg was increased when compared to healthy subjects and dorsal leaf AFOs optimized for energy cost substantially reduced this force and improved impact symmetry when compared to walking without AFO. This indicates that dorsal leaf AFOs may reduce pain resulting from increased impact forces during gait in the contralateral leg in people with unilateral plantar flexor weakness.

Limited knee extension during gait after total knee arthroplasty is related to a low Oxford Knee Score.

BACKGROUND: After total knee replacement (TKR) some patients report low self-perceived function, which is clinically measured using patient reported outcome measures (PROMs). However, PROMs, e.g. the Oxford Knee Score (OKS), inherently lack objective parameters of knee function. Biomechanical gait analysis is an objective and reliable measurement to quantitatively assess joint function. Therefore, the aim of this study was to explore the relationship between biomechanical gait parameters and the OKS. METHODS: Gait analyses were recorded in 37 patients at least one year after primary TKR and in 24 healthy controls. Parameters from this analysis were calculated for hip, knee and ankle joint angles and joint moments in the sagittal and frontal plane including initial contact, early, late stance and swing. For the patients these parameters were expressed as its difference to control values at matched walking speed. Linear regression analyses were performed between the parameters from gait analysis and the OKS, with speed as covariate. RESULTS: The difference in knee extension angle at initial contact and late stance between patients and controls was significantly related to the OKS. Per one degree knee extension difference increase, the OKS reduced with 1.0 to 1.6 points. Overall, patients extended their knee less than controls. Neither ankle and hip gait parameters, nor joint moments showed a relation with OKS. CONCLUSIONS: All patients with a submaximal score on the OKS showed limited knee extension during gait, even without a mechanical constraint in knee extension. This could be related to motor control limitations in this patient group.

Evaluating cost function criteria in predicting healthy gait.

Accurate predictive simulations of human gait rely on optimisation criteria to solve the system's redundancy. Defining such criteria is challenging, as the objectives driving the optimization of human gait are unclear. This study evaluated how minimising various physiologically-based criteria (i.e., cost of transport, muscle activity, head stability, foot-ground impact, and knee ligament use) affects the predicted gait, and developed and evaluated a combined, weighted cost function tuned to predict healthy gait. A generic planar musculoskeletal model with 18 Hill-type muscles was actuated using a reflex-based, parameterized controller. First, the criteria were applied into the base simulation framework separately. The gait pattern predicted by minimising each criterion was compared to experimental data of healthy gait using coefficients of determination (R2) and root mean square errors (RMSE) averaged over all biomechanical variables. Second, the optimal weighted combined cost function was created through stepwise addition of the criteria. Third, performance of the resulting combined cost function was evaluated by comparing the predicted gait to a simulation that was optimised solely to track experimental data. Optimising for each of the criteria separately showed their individual contribution to distinct aspects of gait (overall R2: 0.37-0.56; RMSE: 3.47-4.63 SD). An optimally weighted combined cost function provided improved overall agreement with experimental data (overall R2: 0.72; RMSE: 2.10 SD), and its performance was close to what is maximally achievable for the underlying simulation framework. This study showed how various optimisation criteria contribute to synthesising gait and that careful weighting of them is essential in predicting healthy gait.

Validation of forward simulations to predict the effects of bilateral plantarflexor weakness on gait.

BACKGROUND: Bilateral plantarflexor muscle weakness is a common impairment in many neuromuscular diseases. However, the way in which severity of plantarflexor weakness affects gait in terms of walking energy cost and speed is not fully understood. Predictive simulations are an attractive alternative to human experiments as simulations allow systematic alterations in muscle weakness. However, simulations of pathological gait have not yet been validated against experimental data, limiting their applicability. RESEARCH QUESTION: Our first aim was to validate a predictive simulation framework for walking with bilateral plantarflexor weakness by comparing predicted gait against experimental gait data of patients with bilateral plantarflexor weakness. Secondly, we aimed to evaluate how incremental levels of bilateral plantarflexor weakness affect gait. METHODS: We used a planar musculoskeletal model with 9 degrees of freedom and 9 Hill-type muscle-tendon units per leg. A state-dependent reflex-based controller optimized for a function combining energy cost, muscle activation squared and head acceleration was used to simulate gait. For validation, strength of the plantarflexors was reduced by 80 % and simulated gait compared with experimental data of 16 subjects with bilateral plantarflexor weakness. Subsequently, strength of the plantarflexors was reduced stepwise to evaluate its effect on gait kinematics and kinetics, walking energy cost and speed. RESULTS: Simulations with 80 % weakness matched well with experimental hip and ankle kinematics and kinetics (R > 0.64), but less for knee kinetics (R < 0.55). With incremental strength reduction, especially beyond a reduction of 60 %, the maximal ankle moment and power decreased. Walking energy cost and speed showed a strong quadratic relation (R2>0.82) with plantarflexor strength. SIGNIFICANCE: Our simulation framework predicted most gait changes due to bilateral plantarflexor weakness, and indicates that pathological gait features emerge especially when bilateral plantarflexor weakness exceeds 60 %. Our framework may support future research into the effect of pathologies or assistive devices on gait.

Inter-laboratory comparison of knee biomechanics and muscle activation patterns during gait in patients with knee osteoarthritis.

BACKGROUND: Gait analysis has been used for decades to quantify knee function in patients with knee osteoarthritis; however, it is unknown whether and to what extent inter-laboratory differences affect the comparison of gait data between studies. Therefore, the aim of this study was to perform an inter-laboratory comparison of knee biomechanics and muscle activation patterns during gait of patients with knee osteoarthritis. METHODS: Knee biomechanics and muscle activation patterns from patients with knee osteoarthritis were analyzed, previously collected at Dalhousie University (DAL: n = 55) and Amsterdam UMC, VU medical center (VUmc: n = 39), using their in-house protocols. Additionally, one healthy male was measured at both locations. Both direct comparisons and after harmonization of components of the protocols were made. Inter-laboratory comparisons were quantified using statistical parametric mapping analysis and discrete gait parameters. RESULTS: The inter-laboratory comparison showed offsets in the sagittal plane angles, moments and frontal plane angles, and phase shifts in the muscle activation patterns. Filter characteristics, initial contact identification and thigh anatomical frame definitions were harmonized between the laboratories. After this first step in protocol harmonization, the offsets in knee angles and sagittal plane moments remained, but the inter-laboratory comparison of the muscle activation patterns improved. CONCLUSIONS: Inter-laboratory differences obstruct valid comparisons of gait datasets from patients with knee osteoarthritis between gait laboratories. A first step in harmonization of gait analysis protocols improved the inter-laboratory comparison. Further protocol harmonization is recommended to enable valid comparisons between labs, data-sharing and multicenter trials to investigate knee function in patients with knee osteoarthritis.

Matching walking speed of controls affects identification of gait deviations in patients with a total knee replacement.

BACKGROUND: The assessment of functional recovery of patients after a total knee replacement includes the quantification of gait deviations. Comparisons to comfortable gait of healthy controls may incorrectly suggest biomechanical gait deviations, since the usually lower walking speed of patients already causes biomechanical differences. Moreover, taking peak values as parameter might not be sensitive to actual differences. Therefore, this study investigates the effect of matching walking speed and full-waveform versus discrete analyses. METHODS: Gait biomechanics of 25 knee replacement patients were compared to 22 controls in two ways: uncorrected and corrected for walking speed employing principal component analyses, to reconstruct control gait biomechanics at walking speeds matched to the patients. Ankle, knee and hip kinematics and kinetics were compared over the full gait cycle using statistical parametric mapping against using peak values. FINDINGS: All joint kinematics and kinetics gait data were impacted by applying walking speed correction, especially the kinetics of the knee. The lower control walking speeds used for reference generally reduced the magnitude of differences between patient and control gait, however some were enlarged. Full-waveform analysis identified greater deviating gait cycle regions beyond the peaks, but did not make peak value analyses redundant. INTERPRETATION: Matching walking speed of controls affects identification of gait deviations in patients with a total knee replacement, reducing deviations confounded by walking speed and revealing hidden gait deviations related to possible compensations. Full-waveform analysis should be used along peak values for a comprehensive quantification of differences in gait biomechanics.

Ankle foot orthoses in cerebral palsy: Effects of ankle stiffness on trunk kinematics, gait stability and energy cost of walking.

In children with cerebral palsy (CP), rigid ventral shell ankle-foot orthoses (vAFOs) are often prescribed to reduce excessive knee flexion in stance and lower the energy cost of walking (ECW). However, how vAFOs affect ECW is a complex issue, as vAFOs may have an impact on lower limb biomechanics, upper body movements, and balance. Besides, the vAFO's biomechanical effect have been shown to be dependent on its stiffness around the ankle joint. We examined whether vAFO stiffness influences trunk movements and gait stability in CP, and whether there is a relationship between these factors and ECW. Fifteen children with spastic CP were prescribed vAFOs. Stiffness was varied into a rigid, stiff and flexible configuration. At baseline (shoes-only) and for each vAFO stiffness configuration, 3D-gait analyses and ECW-tests were performed. From the gait analyses, we derived trunk tilt, lateroflexion, and rotation range of motion (RoM) and the mediolateral and anteroposterior Margins of Stability (MoS) and their variability as measures of gait stability. With the ECW-test we determined the netEC. We found that wearing vAFOs significantly increased trunk lateroflexion (Wald χ2 = 33.7, p < 0.001), rotation RoM (Wald χ2 = 20.5, p < 0.001) and mediolateral gait instability (Wald χ2 = 10.4, p = 0.016). The extent of these effects partly depended on the stiffness of the vAFO. Significant relations between trunk movements, gait stability and ECW were found r = 0.57-0.81, p < 0.05), which indicates that trunk movements and gait stability should be taken into account when prescribing vAFOs to improve gait in children with CP walking with excessive knee flexion.

The Human Body Model versus conventional gait models for kinematic gait analysis in children with cerebral palsy.

With the rise of biofeedback in gait training in cerebral palsy there is a need for real-time measurements of gait kinematics. The Human Body Model (HBM) is a recently developed model, optimized for the real-time computing of kinematics. This study evaluated differences between HBM and two commonly used models for clinical gait analysis: the Newington Model, also known as Plug-in-Gait (PiG), and the calibrated anatomical system technique (CAST). Twenty-five children with cerebral palsy participated. 3D instrumented gait analyses were performed in three laboratories across Europe, using a comprehensive retroreflective marker set comprising three models: HBM, PiG and CAST. Gait kinematics from the three models were compared using statistical parametric mapping, and RMSE values were used to quantify differences. The minimal clinically significant difference was set at 5°. Sagittal plane differences were mostly less than 5°. For frontal and transverse planes, differences between all three models for almost all segment and joint angles exceeded the value of minimal clinical significance. Which model holds the most accurate information remains undecided since none of the three models represents a ground truth. Meanwhile, it can be concluded that all three models are equivalent in representing sagittal plane gait kinematics in clinical gait analysis.

Effect of walking with a modified gait on activation patterns of the knee spanning muscles in people with medial knee osteoarthritis.

OBJECTIVE: To evaluate muscle activation patterns and co-contraction around the knee in response to walking with modified gait patterns in patients with medial compartment knee-osteoarthritis (KOA). DESIGN: 40 medial KOA patients walked on an instrumented treadmill. Surface EMG activity from seven knee-spanning muscles (gastrocnemius, hamstrings, quadriceps), kinematics, and ground reaction forces were recorded. Patients received real-time visual feedback on target kinematics to modify their gait pattern towards three different gait modifications: Toe-in, Wider steps, Medial Thrust. The individualized feedback aimed to reduce their first peak knee adduction moment (KAM) by ≥10%. Changes in muscle activations and medial/lateral co-contraction index during the loading response phase (10-35% of the gait cycle) were evaluated, for the steps in which ≥10% KAM reduction was achieved. RESULTS: Data from 30 patients were included in the analyses; i.e. all who could successfully reduce their KAM in a sufficient number of steps by ≥10%. When walking with ≥10% KAM reduction, Medial Thrust gait (KAM -31%) showed increased flexor activation (24%), co-contraction (17%) and knee flexion moment (35%). Isolated wider-step gait also reduced the KAM (-26%), but to a smaller extent, but without increasing muscle activation amplitudes and co-contraction. Toe-in gait showed the greatest reduction in the KAM (-35%), but was accompanied by an increased flexor activation of 42% and hence an increased co-contraction index. CONCLUSION: Gait modifications that are most effective in reducing the KAM also yield an increase in co-contraction, thereby compromising at least part of the effects on net knee load.

The validity and usability of an eight marker model for avatar-based biofeedback gait training.

BACKGROUND: Virtual reality presents a platform for therapeutic gaming, and incorporation of immersive biofeedback on gait may enhance outcomes in rehabilitation. Time is limited in therapeutic practice, therefore any potential gait training tool requires a short set up time, while maintaining clinical relevance and accuracy. The aim of this study was to develop, validate, and establish the usability of an avatar-based application for biofeedback-enhanced gait training with minimal set up time. METHODS: A simplified, eight marker model was developed using eight passive markers placed on anatomical landmarks. This allowed for visualisation of avatar-based biofeedback on pelvis kinematics, hip and knee sagittal angles in real-time. Retrospective gait analysis data from typically developing children (n = 41) and children with cerebral palsy (n = 25), were used to validate eight marker model. Gait outcomes were compared to the Human Body Model using statistical parametric mapping. Usability for use in clinical practice was tested in five clinical rehabilitation centers with the system usability score. FINDINGS: Gait outcomes of Human Body Model and eight marker model were comparable, with small differences in gait parameters. The discrepancies between models were <5°, except for knee extension where eight marker model showed significantly less knee extension, especially towards full extension. The application was considered of 'high marginal acceptability' (system usability score, mean 68 (SD 13)). INTERPRETATION: Gait biofeedback can be achieved, to acceptable accuracy for within-session gait training, using an eight marker model. The application may be considered usable and implemented for use in patient populations undergoing gait training.

Precision of determining bone pose and marker position in the foot and lower leg from computed tomography scans: How low can we go in radiation dose?

Computed tomography (CT) imaging can be used to determine bone pose, sometimes combined with skin-mounted markers. For this specific application, a lower radiation dose than the conventional clinical dose might suffice. This study aims to determine how lowering the radiation dose of a CT-scan of the ankle and foot affects the precision of detecting bone pose and marker position. Radiation dose is proportional to tube charge. Hence, an adult cadaveric leg was scanned 10 times at four different tube charges (150, 75, 50 and 20 mAs) with a Philips Brilliance 64 CT scanner. Precision of detecting bone and marker position at 50 mAs was not significantly different from 75 mAs and from the clinically used 150 mAs, but higher than 20 mAs. Furthermore, no differences of the precision in detecting bone orientation were found. These results indicate that the radiation dose can be reduced by a factor 3 compared to the clinically usual radiation dose, without affecting the precision of detecting bone pose and marker position in the foot and ankle.

Gait retraining using real-time feedback in patients with medial knee osteoarthritis: Feasibility and effects of a six-week gait training program.

BACKGROUND: The knee adduction moment (KAM) is often elevated in medial knee osteoarthritis (KOA). The aim of this study was to evaluate effects on KAM and patient-reported outcomes of a six-week gait training program. METHODS: Twenty-one patients (61 ±â€¯6 years) with KOA participated in a six-week biofeedback training program to encourage increased toe-in (all patients) and increased step-width (five patients). Patients received real-time visual feedback while walking on an instrumented treadmill. We analysed the effect of the gait modification(s) on peak KAM in week six and three and six months post-training. We also evaluated the effect on pain and functional ability. RESULTS: Of 21 patients starting the program, 16 completed it with high attendance (15 and 16 respectively) at the three and six month follow-ups. First peak KAM was significantly reduced by up to 14.0% in week six with non-significant reductions of 8.2% and 5.5% at the follow-ups. Functional ability (assessed using the WOMAC questionnaire) improved significantly after the training (eight point reduction, p = 0.04 in week six and nine point reduction, p = 0.04 at six-month follow-up). There was also a trend towards reduction in WOMAC pain (p = 0.06) at follow-up. CONCLUSIONS: Biofeedback training to encourage gait modifications is feasible and leads to short-term benefits. However, at follow-up, reductions in KAM were less pronounced in some participants suggesting that to influence progression of KOA in the longer term, a permanent regime to reinforce the effects of the training program is needed. Trial number: ISRCTN14687588.

The effect of intravenous iron therapy on long-term survival in anaemic colorectal cancer patients: Results from a matched cohort study.

INTRODUCTION: Intravenous iron therapy has been shown to be advantageous in treating anaemia and reducing the need for blood transfusions. Iron treatment, however, may also be hazardous by supporting cancer growth. Present clinical study explores, for the first time, the effect of preoperative intravenous iron therapy on tumour prognosis in anaemic colorectal cancer patients. METHODS: A retrospective cohort study was performed on consecutive patients who underwent surgery for colorectal cancer between 2010 and 2016 in a single teaching hospital. The primary outcomes were 5-year overall survival (OS) and disease-free survival (DFS). Survival estimates were calculated using the Kaplan-Meier method and patients were matched based on propensity score. RESULTS: 320 (41.0%) of all eligible patients were anaemic, of whom 102 patients received preoperative intravenous iron treatment (31.9%). After propensity score matching 83 patients were included in both intravenous and non-intravenous iron group. The estimated 1-, 3-, and 5-year OS (91.6%, 73.1%, 64.3%, respectively) and DFS (94.5%, 86.7%, 83.4%, respectively) in the intravenous iron group were comparable with the non-intravenous iron group (p = 0.456 and p = 0.240, respectively). In comparing patients with an event (death or recurrence) and no event in the intravenous iron group, a distinct trend was found for decreased transferrin in the event group (median 2.53  g/L vs 2.83  g/L, p = 0.052). CONCLUSION: The present study illustrates that a dose of 1000-2000 mg preoperative intravenous iron therapy does not have a profound effect on long-term overall and disease-free survival in anaemic colorectal cancer patients. Future randomised trials with sufficient power are required to draw definite conclusions on the safety of intravenous iron therapy.

Relationship between knee joint contact forces and external knee joint moments in patients with medial knee osteoarthritis: effects of gait modifications.

OBJECTIVE: To evaluate 1) the relationship between the knee contact force (KCF) and knee adduction and flexion moments (KAM and KFM) during normal gait in people with medial knee osteoarthritis (KOA), 2) the effects on the KCF of walking with a modified gait pattern and 3) the relationship between changes in the KCF and changes in the knee moments. METHOD: We modeled the gait biomechanics of thirty-five patients with medial KOA using the AnyBody Modeling System during normal gait and two modified gait patterns. We calculated the internal KCF and evaluated the external joint moments (KAM and KFM) against it using linear regression analyses. RESULTS: First peak medial KCF was associated with first peak KAM (R2 = 0.60) and with KAM and KFM (R2 = 0.73). Walking with both modified gait patterns reduced KAM (P = 0.002) and the medial to total KCF ratio (P < 0.001) at the first peak. Changes in KAM during modified gait were moderately associated with changes in the medial KCF at the first peak (R2 = 0.54 and 0.53). CONCLUSIONS: At the first peak, KAM is a reasonable substitute for the medial contact force, but not at the second peak. First peak KFM is also a significant contributor to the medial KCF. At the first peak, walking with a modified gait reduced the ratio of the medial to total KCF but not the medial KCF itself. To determine the effects of gait modifications on cartilage loading and disease progression, longitudinal studies and individualized modeling, accounting for motion control, would be required.

Iron therapy as treatment of anemia: A potentially detrimental and hazardous strategy in colorectal cancer patients.

In colorectal cancer patients, iron therapy, and especially intravenous iron therapy, is increasingly used to treat anemia and reduce the use of blood transfusions. However, iron has also been shown to be an essential nutrient for rapidly proliferating tissues and cells. In this respect, anemia of inflammation, characterized by limited duodenal iron uptake and sequestration of iron into the reticuloendothelial system, might be regarded as a potentially effective defense strategy of the human body against tumor growth. We therefore hypothesize that iron therapy, by supporting colorectal tumor growth and increasing the metastatic potential, may worsen tumor prognosis in colorectal cancer patients. This hypothesis is particularly supported for colorectal cancer by laboratory, epidemiological and animal studies, demonstrating the role of iron in all aspects of tumor development growth. Compared to non-malignant colon cells, tumor cells differ in the levels and activity of many iron import and export proteins, resulting in an increase in intracellular iron level and enhanced proliferation. In addition, it is demonstrated that iron is able to amplify Wnt signaling in tumors with Apc mutation, a critical mutation in the development of colorectal cancer. If our hypothesis is to be confirmed, current practice of iron administration, as treatment for anemia and as replacement of blood transfusions, can be hazardous and should be completely reconsidered.

A prospective 24 months follow-up of a three component press-fit prosthesis for hallux rigidus.

BACKGROUND: The aim of this study was to evaluate the results following total first metatarsophalangeal (FMTP) joint replacement arthroplasty using a modular three component press fit prosthesis at two year follow up. METHODS: All patient data was collected in a prospective way in four study centres. Both preoperative and postoperative evaluation consisted of an assessment using the AOFAS-HMI score, visual analogue scale for pain, evaluation of the range of motion and patient satisfaction scores. Postoperative X-rays were reviewed for loosening and radiolucency up to two years. RESULTS: Fifty-five feet were available for analysis at 24 months. Two implants were removed during the study. Six more feet had additional surgery due to stiffness or malalignment. Postoperative AOFAS-HMI scores improved significantly by 32.4 points at two year follow-up (p<0.001). The visual analogue scale for pain improved significantly from 6.8 (std 1,6) preoperatively to 1.6 (std 1,9) postoperatively (p<0.0001). Mean dorsiflexion improved from 12.6 (std 10,1) degrees preoperatively to 31.2 (std 16,8) degrees postoperatively. Eighty-seven percent of patients were moderately to well satisfied with the end result. Eighteen prostheses showed radiolucency at 24 months. CONCLUSION: Implantation of a Metis® modular three component press fit prosthesis for the metatarsophalangeal joint in hallux rigidus shows significant improvement in AOFAS-HMI scores and a decrease in pain. Concerns remain with regard to early reoperation rate (14.5%) and long term survival of the implant. Future studies will have to address these aspects.