Changes and Associations Between Gait Biomechanics and Knee Inflammation After Aspiration and Glucocorticoid Injection for Knee Osteoarthritis.

OBJECTIVE: Although knee inflammation is thought to adversely affect joint function in patients with knee osteoarthritis (OA), the effects of reducing knee inflammation on gait biomechanics and strength are unknown. Our objectives were to compare ultrasound (US) measures of knee inflammation, gait biomechanics, knee extension and flexion strength, and pain before and after knee aspiration and glucocorticoid injection, and to explore associations among changes. METHODS: Forty-nine patients (69 knees) with symptomatic knee OA and synovitis were tested before and 3-4 weeks after US-guided knee aspiration and glucocorticoid injection. At each visit, participants completed US assessments for inflammatory features of knee OA, 3D gait analysis, isokinetic knee extension and flexion strength tests, and Knee Osteoarthritis Outcome Score (KOOS) pain subscales. Linear and polynomial mixed-effects regression models were used to investigate changes and their associations. RESULTS: Changes were observed for the synovitis score (unstandardized ß [post-injection minus pre-injection] -0.55/9 [95% confidence interval (95% CI) -0.97, -0.12]), effusion depth (-1.05 mm [95% CI -1.07, -0.39]), KOOS pain (unstandardized ß 5.91/100 [95% CI 1.86, 9.97]), peak external knee flexion and extension moments (KFM; 3.33 Nm [95% CI 0.45, 6.22]), KEM (-2.99 Nm [95% CI -5.93, -0.05]), and knee extension strength (4.70 Nm [95% CI 0.39, 9.00]) and flexion strength (3.91 Nm [95% CI 1.50, 6.81]). The external KFM increased during 13-38% and 76-89% of stance post-injection. When controlled for time, greater synovitis was associated with lower knee extension strength, while lower pain was associated with increased knee extension and flexion strength. CONCLUSION: In patients with knee OA and synovitis, reduced inflammation and pain after aspiration and glucocorticoid injection are associated with changes in knee gait biomechanics and strength.

Advocating for Implementation of the Global Action Plan on Physical Activity: Challenges and Support Requirements.

BACKGROUND: There is limited understanding of the challenges experienced and supports required to aid effective advocacy of the Global Action Plan on Physical Activity (GAPPA). The purpose of this study was to assess the challenges experienced and supports needed to advocate for the GAPPA across countries of different income levels. METHODS: Stakeholders working in an area related to the promotion of physical activity were invited to complete an online survey. The survey assessed current awareness and engagement with the GAPPA, factors related to advocacy, and the perceived challenges and supports related to advocacy for implementation of the GAPPA. Closed questions were analyzed in SPSS, with a Pearson's chi-square test used to assess differences between country income level. Open questions were analyzed using inductive thematic analysis. RESULTS: Participants (n = 518) from 81 countries completed the survey. Significant differences were observed between country income level for awareness of the GAPPA and perceived country engagement with the GAPPA. Challenges related to advocacy included a lack of support and engagement, resources, priority, awareness, advocacy education and training, accessibility, and local application. Supports needed for future advocacy included guidance and support, cooperation and alliance, advocacy education and training, and advocacy resources. CONCLUSIONS: Although stakeholders from different country income levels experience similar advocacy challenges and required supports, how countries experience these can be distinct. This research has highlighted some specific ways in which those involved in the promotion of physical activity can be supported to scale up advocacy for the GAPPA. When implementing such supports, consideration of regional, geographic, and cultural barriers and opportunities is important to ensure they are effective and equitable.

Test-Retest Reliability and Sensitivity to Change of Ultrasound-Based Methods of Measuring Synovial Inflammation in Knee Osteoarthritis.

OBJECTIVES: To assess test-retest reliability of musculoskeletal ultrasound (US) measures of inflammation in patients with knee osteoarthritis (OA) and to assess the sensitivity to change of US measures of inflammation in patients with knee OA. METHODS: To mimic a common clinical scenario, 36 patients (n = 70 knees) with symptomatic knee OA who were in stable condition underwent 2 assessments within 14 days by different operators and different US machines, graded by a single rater. Test-retest reliability was measured using Cohen's kappa coefficient, intraclass correlation coefficient (ICC), and absolute agreement parameters. A total of 51 patients (n = 72 knees) were tested immediately before and 21-28 days after intraarticular glucocorticoid injection to investigate sensitivity to change and longitudinal construct validity. Paired t-tests and standardized response mean (SRM) were used to assess sensitivity to change. Multivariate linear regression was used to investigate longitudinal construct validity of US with Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scores, while adjusting for covariates. RESULTS: US measures of inflammation demonstrated moderate (κ = 0.41, 0.60) to substantial (κ = 0.61, 0.80) agreement. Quantitative measures of synovitis and effusion demonstrated good test-retest reliability (ICC2,1 0.71, 0.92). US measures of synovitis and effusion demonstrated low-to-moderate sensitivity to change (SRM -0.29, -0.50). The associations between changes in US measures and KOOS pain scores over time were low, and 95% confidence intervals included zero. CONCLUSION: In a clinical setting, US measures of inflammatory features of knee OA have substantial reliability and low-to-moderate sensitivity to change, whereas measures of structural OA features are less reliable. Longitudinal construct validity of US measures of synovitis and effusion to KOOS pain scores is not strongly supported.

Performance of 5-Strand Hamstring Autograft Anterior Cruciate Ligament Reconstruction in the STABILITY Study: A Subgroup Analysis.

BACKGROUND: Anterior cruciate ligament (ACL) reconstructions (ACLRs) with graft diameters <8mm have been shown to have higher revision rates. The 5-strand (5S) hamstring autograft configuration is a proposed option to increase graft diameter. PURPOSE: To investigate the differences in clinical outcomes between 4-strand (4S) and 5S hamstring autografts for ACLR in patients who underwent ACLR alone or concomitantly with a lateral extra-articular tenodesis (LET) procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Data from the STABILITY study were analyzed to compare a subgroup of patients undergoing ACLR alone or with a concomitant LET procedure (ACLR + LET) with a minimum graft diameter of 8mm that had either a 4S or 5S hamstring autograft configuration. The primary outcome was clinical failure, a composite of rotatory laxity and/or graft failure. The secondary outcome measures consisted of 2 patient-reported outcome scores (PROs)-namely, the ACL Quality of Life Questionnaire (ACL-QoL) and the International Knee Documentation Committee (IKDC) score at 24 months postoperatively. RESULTS: Of the 618 patients randomized in the STABILITY study, 399 (228 male; 57%) fit the inclusion criteria for this study. Of these, 191 and 208 patients underwent 4S and 5S configurations of hamstring ACLR, respectively, with a minimum graft diameter of 8mm. Both groups had similar characteristics other than differences in anthropometric factors-namely, sex, height, and weight, and Beighton scores. The primary outcomes revealed no difference between the 2 groups in rotatory stability (odds ratio [OR], 1.19; 95% CI, 0.77-1.84; P = .42) or graft failure (OR, 1.13; 95% CI, 0.51-2.50; P = .76). There was no significant difference between the groups in Lachman (P = .46) and pivot-shift (P = .53) test results at 24 months postoperatively. The secondary outcomes revealed no differences in the ACL-QoL (P = .67) and IKDC (P = .83) scores between the 2 subgroups. CONCLUSION: At the 24-month follow-up, there were no significant differences in clinical failure rates and PROs in an analysis of patients with 4S and 5S hamstring autografts of ≥8mm diameter for ACLR or ACLR + LET. The 5S hamstring graft configuration is a viable option to produce larger-diameter ACL grafts.

Predictors of Graft Failure in Young Active Patients Undergoing Hamstring Autograft Anterior Cruciate Ligament Reconstruction With or Without a Lateral Extra-articular Tenodesis: The Stability Experience.

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction (ACLR) has higher failure rates in young active patients returning to sports as compared with older, less active individuals. Augmentation of ACLR with an anterolateral procedure has been shown to reduce failure rates; however, indications for this procedure have yet to be clearly defined. PURPOSE/HYPOTHESIS: The purpose of this study was to identify predictors of ACL graft failure in high-risk patients and determine key indications for when hamstring ACLR should be augmented by a lateral extra-articular tenodesis (LET). We hypothesized that different preoperative characteristics and surgical variables may be associated with graft failure characterized by asymmetric pivot shift and graft rupture. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data were obtained from the Stability 1 Study, a multicenter randomized controlled trial of young active patients undergoing autologous hamstring ACLR with or without a LET. We performed 2 multivariable logistic regression analyses, with asymmetric pivot shift and graft rupture as the dependent variables. The following were included as predictors: LET, age, sex, graft diameter, tear chronicity, preoperative high-grade knee laxity, preoperative hyperextension on the contralateral side, medial meniscal repair/excision, lateral meniscal repair/excision, posterior tibial slope angle, and return-to-sports exposure time and level. RESULTS: Of the 618 patients in the Stability 1 Study, 568 with a mean age of 18.8 years (292 female; 51.4%) were included in this analysis. Asymmetric pivot shift occurred in 152 (26.8%) and graft rupture in 43 (7.6%). The addition of a LET (odds ratio [OR], 0.56; 95% CI, 0.37-0.83) and increased graft diameter (OR, 0.62; 95% CI, 0.44-0.87) were significantly associated with lower odds of asymmetric pivot shift. The addition of a LET (OR, 0.40; 95% CI, 0.18-0.91) and older age (OR, 0.83; 95% CI, 0.72-0.96) significantly reduced the odds of graft rupture, while greater tibial slope (OR, 1.15; 95% CI, 1.01-1.32), preoperative high-grade knee laxity (OR, 3.27; 95% CI, 1.45-7.41), and greater exposure time to sport (ie, earlier return to sport) (OR, 1.18; 95% CI, 1.08-1.29) were significantly associated with greater odds of rupture. CONCLUSION: The addition of a LET and larger graft diameter were significantly associated with reduced odds of asymmetric pivot shift. Adding a LET was protective of graft rupture, while younger age, greater posterior tibial slope, high-grade knee laxity, and earlier return to sport were associated with increased odds of graft rupture. Orthopaedic surgeons should consider supplementing hamstring autograft ACLR with a LET in young active patients with morphological characteristics that make them at high risk of reinjury.

Synovitis Is Associated With Constant Pain in Knee Osteoarthritis: A Cross-sectional Study of OMERACT Knee Ultrasound Scores.

OBJECTIVE: To examine the association between ultrasound (US)-detected knee inflammation and intermittent and constant pain experiences in patients with knee osteoarthritis (OA). METHODS: Participants with radiographically early-stage (Kellgren-Lawrence arthritis grading scale [KL] ≤ 2) and late-stage (KL ≥ 3) disease and frequent symptoms underwent musculoskeletal US measures of inflammation using the Outcome Measures in Rheumatology (OMERACT) knee US scoring system. Pain experiences were captured using the Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) tool. We assessed the association between US-synovitis and ICOAP pain experiences using a series of linear, logistic, or multinomial logistic regression models (as appropriate for each variable), while adjusting for age, sex, BMI, and radiographic stage. Secondary analyses were performed similarly by radiographic stage. RESULTS: Pain and synovitis measures from 248 patients (453 knees) were included. Worse synovitis was associated with higher ICOAP constant pain scores (ß 8.05, 95% CI 0.67-15.43), but not intermittent pain scores. Moderate-to-severe synovitis was associated with a 4.73-fold increased relative risk (95% CI 1.06-17.00) of a constant pain pattern. In secondary analyses, moderate-to-severe synovitis in early radiographic OA was associated with 2.70-higher odds (95% CI 1.04-7.02) of any constant pain, 3.28-higher odds (95% CI 1.43-7.52) of any intermittent pain, and with higher intermittent (ß 10.47, 95% CI 1.03-19.91) and constant (ß 12.62, 95% CI 3.02-22.23) pain scores. No associations were identified for synovitis in those with late radiographic OA. CONCLUSION: In patients with knee OA, moderate-to-severe synovitis is most strongly associated with constant pain. Inflammation may play context-specific roles across pain experiences, especially in earlier radiographic stages of knee OA.

A qualitative dominant mixed methods exploration of novel educational material for patients considering total knee arthroplasty.

PURPOSE: To optimize non-operative management and decision making surrounding TKR we created educational whiteboard videos for patients with knee OA. The purpose of this study was to pilot our educational videos with end-users (patients) to determine patients' experiences and perspectives regarding the content and clarity of videos and to better understand their potential impact on patient's health behaviour. MATERIALS AND METHODS: This was a mixed methods evaluation, using a qualitative descriptive approach, of patients attending their first consultation with an arthroplasty surgeon for TKR. We conducted in-depth semi-structured interviews with patients. Three members of the research team coded data independently, implementing a thematic analysis. RESULTS: Thirteen participants were included. Participants indicated that the videos enhanced their confidence and clarity surrounding their decision to undergo TKR. The videos also addressed several knowledge gaps in their understanding of OA management. Barriers to uptake of the education were identified including limited access to PTs and the challenge of weight loss. Conclusions: The current educational intervention was valued by patients with knee OA. Implementation of these videos may have important implications for patients, providers, and our health care system.IMPLICATIONS FOR REHABILITATIONPatients with knee OA referred by primary care physicians to arthroplasty surgeons have knowledge gaps that may influence their self-management and decision making surrounding their condition.Educational materials can address these gaps and support patients in their understanding and management of their condition, which may have important downstream implications.Barriers to accessing non-operative care including physiotherapy must be pre-emptively addressed to ensure that enhanced knowledge is met with improved access for patients.

Association of Ligamentous Laxity, Male Sex, Chronicity, Meniscal Injury, and Posterior Tibial Slope With a High-Grade Preoperative Pivot Shift: A Post Hoc Analysis of the STABILITY Study.

BACKGROUND: A spectrum of anterolateral rotatory laxity exists in anterior cruciate ligament (ACL)-injured knees. Understanding of the factors contributing to a high-grade pivot shift continues to be refined. PURPOSE: To investigate factors associated with a high-grade preoperative pivot shift and to evaluate the relationship between this condition and baseline patient-reported outcome measures (PROMs). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A post hoc analysis was performed of 618 patients with ACL deficiency deemed high risk for reinjury. A binary logistic regression model was developed, with high-grade pivot shift as the dependent variable. Age, sex, Beighton score, chronicity of the ACL injury, posterior third medial or lateral meniscal injury, and tibial slope were selected as independent variables. The importance of knee hyperextension as a component of the Beighton score was assessed using receiver operator characteristic curves. Baseline PROMs were compared between patients with and without a high-grade pivot. RESULTS: Six factors were associated with a high-grade pivot shift: Beighton score (each additional point; odds ratio [OR], 1.17; 95% CI, 1.06-1.30; P = .002), male sex (OR, 2.30; 95% CI, 1.28-4.13; P = .005), presence of a posterior third medial (OR, 2.55; 95% CI, 1.11-5.84; P = .03) or lateral (OR, 1.76; 95% CI, 1.01-3.08; P = .048) meniscal injury, tibial slope >9° (OR, 2.35; 95% CI, 1.09-5.07; P = .03), and chronicity >6 months (OR, 1.70; 95% CI, 1.00-2.88; P = .049). The presence of knee hyperextension improved the diagnostic utility of the Beighton score as a predictor of a high-grade pivot shift. Tibial slope <9° was associated with only a high-grade pivot in the presence of a posterior third medial meniscal injury. Patients with a high-grade pivot shift had higher baseline 4-Item Pain Intensity Measure scores than did those without a high-grade pivot shift (mean ± SD, 11 ± 13 vs 8 ± 14; P = .04); however, there was no difference between groups in baseline International Knee Documentation Committee, ACL Quality of Life, Knee injury and Osteoarthritis Outcome Score, or Knee injury and Osteoarthritis Outcome Score subscale scores. CONCLUSION: Ligamentous laxity, male sex, posterior third medial or lateral meniscal injury, increased posterior tibial slope, and chronicity were associated with a high-grade pivot shift in this population deemed high risk for repeat ACL injury. The effect of tibial slope may be accentuated by the presence of meniscal injury, supporting the need for meniscal preservation. Baseline PROMs were similar between patients with and without a high-grade pivot shift.

Associations Between Cadence and Knee Loading in Patients With Knee Osteoarthritis.

OBJECTIVE: To test the hypothesis that higher walking cadence is associated with lower knee loading, while controlling for walking speed, in patients with medial compartment tibiofemoral osteoarthritis (OA). METHODS: A total of 691 patients underwent quantitative gait analysis, including 3-dimensional knee moments and temporospatial parameters. Using multivariate linear regression, we tested the association of walking cadence with the knee adduction moment angular impulse (a surrogate measure of medial knee compartment load throughout the stance), while controlling for walking speed. We repeated the analysis while also adjusting for sex, age, body mass index, radiographic OA, knee pain, lateral trunk lean, foot progression angle, and mechanical axis angle, and while replacing the knee adduction moment angular impulse with other surrogate measures of knee loading. RESULTS: While controlling for walking speed, we found that a lower cadence was associated with higher knee adduction moment angular impulse (standardized ß = -0.396, P < 0.001), suggesting a 0.02% body weight × height × seconds (%BW × Ht × s) decrease in impulse for each step per minute increase in cadence (unstandardized ß -0.020 %BW × Ht × s [95% confidence interval -0.027, -0.015]), and remained consistent after adjusting for covariates. A lower cadence was also associated with higher first (standardized ß = -0.138, P = 0.010) and second peak knee adduction moment (standardized ß = -0.132, P = 0.018), higher peak knee flexion moment (standardized ß = -0.128, P = 0.049), and vertical ground reaction force (standardized ß = -0.116, P = 0.035) in the adjusted analyses. CONCLUSION: When controlling for walking speed, we found that a lower cadence is associated with higher knee loading per step in patients with medial tibiofemoral OA. Future research should investigate the potential beneficial biomechanical and clinical effects of increasing walking cadence in patients with knee OA.

Reliability and validity of knee angles and moments in patients with osteoarthritis using a treadmill-based gait analysis system.

BACKGROUND: Although commonly used to study knee osteoarthritis (OA), relatively little is known about the reliability and validity of three-dimensional (3D) gait biomechanics derived from treadmill-based systems. RESEARCH QUESTION: Using a treadmill-based gait analysis system, our objectives were to: 1) estimate the test-retest reliability of frontal and sagittal plane knee angles and moments in knee OA patients; 2) examine concurrent validity by estimating the associations between treadmill-based and overground (gold standard) measures; and 3) examine known-groups validity by comparing measures between knee OA patients and matched healthy controls. METHODS: 34 patients and 16 controls completed 3D gait analyses using treadmill-based and overground systems. Treadmill walking speed was matched to self-selected overground speed. Marker set, knee angle and moment calculations were consistent for both systems. Patients completed a second test session using the treadmill-based system <24 h later but within 1 week of the first test session. Variables calculated from knee angle and moment gait waveforms during stance were evaluated using Bland and Altman plots, Intraclass Correlation Coefficients (ICC), Pearson correlations (r) and t-tests. RESULTS: Visual inspection of the Bland and Altman plots did not reveal any systematic differences between test and retest sessions; however, limits of agreement (LoA) were larger for the sagittal plane than the frontal plane. Mean differences between sessions for knee angles were <0.25 degrees and <0.18 %BW*ht for knee moments. ICCs ranged from 0.57-to-0.93 for test-retest reliability. Pearson correlations between treadmill and overground systems ranged from 0.56-to-0.97. Although highly associated, there were substantial differences in the moments, emphasizing they cannot be used interchangeably. Patients had greater first peak knee adduction moments (KAM) than controls [mean difference (95 %CI): 0.55 (-1.07, -0.04), p = 0.03]. SIGNIFICANCE: Results suggest frontal and sagittal plane knee angles and moments in patients with knee OA evaluated using a treadmill-based system are reliable and valid.

Lateral Extra-articular Tenodesis Reduces Failure of Hamstring Tendon Autograft Anterior Cruciate Ligament Reconstruction: 2-Year Outcomes From the STABILITY Study Randomized Clinical Trial.

BACKGROUND: Persistent anterolateral rotatory laxity after anterior cruciate ligament (ACL) reconstruction (ACLR) has been correlated with poor clinical outcomes and graft failure. HYPOTHESIS: We hypothesized that a single-bundle, hamstring ACLR in combination with a lateral extra-articular tenodesis (LET) would reduce the risk of ACLR failure in young, active individuals. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This is a multicenter, prospective, randomized clinical trial comparing a single-bundle, hamstring tendon ACLR with or without LET performed using a strip of iliotibial band. Patients 25 years or younger with an ACL-deficient knee were included and also had to meet at least 2 of the following 3 criteria: (1) grade 2 pivot shift or greater, (2) a desire to return to high-risk/pivoting sports, (3) and generalized ligamentous laxity (GLL). The primary outcome was ACLR clinical failure, a composite measure of rotatory laxity or a graft rupture. Secondary outcome measures included the P4 pain scale, Marx Activity Rating Scale, Knee injury Osteoarthritis and Outcome Score (KOOS), International Knee Documentation Committee score, and ACL Quality of Life Questionnaire. Patients were reviewed at 3, 6, 12, and 24 months postoperatively. RESULTS: A total of 618 patients (297 males; 48%) with a mean age of 18.9 years (range, 14-25 years) were randomized. A total of 436 (87.9%) patients presented preoperatively with high-grade rotatory laxity (grade 2 pivot shift or greater), and 215 (42.1%) were diagnosed as having GLL. There were 18 patients lost to follow-up and 11 who withdrew (~5%). In the ACLR group, 120/298 (40%) patients sustained the primary outcome of clinical failure, compared with 72/291 (25%) in the ACLR+LET group (relative risk reduction [RRR], 0.38; 95% CI, 0.21-0.52; P < .0001). A total of 45 patients experienced graft rupture, 34/298 (11%) in the ACLR group compared with 11/291 (4%) in the ACL+LET group (RRR, 0.67; 95% CI, 0.36-0.83; P < .001). The number needed to treat with LET to prevent 1 patient from graft rupture was 14.3 over the first 2 postoperative years. At 3 months, patients in the ACLR group had less pain as measured by the P4 (P = .003) and KOOS (P = .007), with KOOS pain persisting in favor of the ACLR group to 6 months (P = .02). No clinically important differences in patient-reported outcome measures were found between groups at other time points. The level of sports activity was similar between groups at 2 years after surgery, as measured by the Marx Activity Rating Scale (P = .11). CONCLUSION: The addition of LET to a single-bundle hamstring tendon autograft ACLR in young patients at high risk of failure results in a statistically significant, clinically relevant reduction in graft rupture and persistent rotatory laxity at 2 years after surgery. REGISTRATION: NCT02018354 ( ClinicalTrials.gov identifier).

Strong independent associations between gait biomechanics and pain in patients with knee osteoarthritis.

We investigated the simple and multivariate associations between knee pain and gait biomechanics. 279 patients with medial knee osteoarthritis (OA) and discordant changes in pain between limbs after walking completed bilateral three-dimensional gait analysis. For each limb, patients rated their pain before and after a 6-min walk and the change in pain was recorded as an increase (≥1 points) or not (≤0 points). Among paired limbs, the simple and multivariate associations between an increase in pain and the external moments in each orthogonal plane were evaluated using conditional logistic regression. The analyses were then repeated for knee angles. Univariate analyses demonstrated associations in each plane that varied in both magnitude and direction, with larger associations for the knee moments [Odds Ratio (95% confidence interval) = first peak adduction moment: 2.80 (2.02, 3.88), second peak adduction moment: 2.36 (1.73, 3.24), adduction impulse: 6.65 (3.50, 12.62), flexion moment: 0.46 (0.36, 0.60), extension moment: 0.56 (0.44, 0.71), internal rotation moment: 7.54 (3.32, 17.13), external rotation moment: 0.001 (0.00, 0.04)]. Multivariate analyses with backward elimination resulted in a model including only the adduction impulse [5.35 (2.51, 11.42)], flexion moment [0.32 (0.22, 0.46)] and extension moment [0.28 (0.19, 0.42)]. The varus, flexion and extension angles were included in the final multivariate model for the knee angles. When between-person confounding is lessened by comparing limbs within patients, there are strong independent associations between knee pain and multiple external knee moments that vary in magnitude and direction. While controlling for other knee moments, a greater adduction impulse and lower flexion and extension moments were independently associated with greater odds of an increase in pain.

Gait biomechanics after combined HTO-ACL reconstruction versus HTO alone: A matched cohort study.

The purpose of the present study was to compare bilateral external knee moments during gait in patients with concomitant medial compartment knee OA, varus alignment and chronic anterior cruciate ligament (ACL) deficiency who underwent either medial opening-wedge high tibial osteotomy alone (HTO) or simultaneous HTO and ACL reconstruction (HTO-ACLR). Fifty-two patients (26 matched pairs) completed 3D gait analysis preoperatively and at a minimum 5 years postoperatively. Patients were matched for preoperative age, sex, body mass index and magnitude of correction. Primary outcomes selected a priori were the peak knee adduction moment (KAM) and knee flexion (KFM) moment during stance. Moments were compared using mixed model repeated measures analysis of variance (ANOVA). For the peak KAM, there was a significant time by limb interaction. For both groups, there were similar reductions in the peak KAM 5 years postoperatively in the surgical limb only [-1.34 %BW × Ht (-1.71, -0.96) and -1.72 %BW × Ht (-1.99, -1.44) for HTO and HTO-ACLR, respectively]. For the peak KFM, there was a significant time by group by limb interaction. There was a decrease in the peak KFM 5 years postoperatively in the HTO group [-0.88 %BW × Ht (-1.45, -0.31)] but not in the HTO-ACLR group [0.03 %BW × Ht (-0.43, 0.48)]. These results suggest that individuals with medial knee OA, varus alignment and chronic ACL deficiency who undergo simultaneous medial opening-wedge HTO and ACL reconstruction may not experience the same long-term (5 year) changes in sagittal plane knee biomechanics observed in patients undergoing HTO alone. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy.

Defects in apoptosis mechanisms contribute to chemoresistance in malignancy. However, correlations of apoptosis-regulating proteins with clinical outcome in cancer patients are variable, presumably reflecting the difficulty of using static tests of gene expression in a scenario influenced by a dynamic interplay of multiple pro- and antiapoptotic molecules. Therefore, we assessed the functional integrity of apoptosis pathways in intact primary leukemia cells and correlated the functional status of these pathways with clinical outcome. Active apoptogenic proteins were introduced into primary leukemia cells by electroporation followed by measurement of active caspases by flow cytometric techniques. Cytochrome c was introduced to activate the intrinsic (mitochondrial) pathway, whereas caspase-8 was introduced to activate the extrinsic (death receptor) pathway. In a series of 24 patients with acute myeloid leukemia, 79% had a block in at least one pathway, indicating that defects in caspase activation mechanisms are common in patients with leukemia. Simultaneous blocks in both pathways correlated with chemoresistant disease (92% of patients with chemoresistant disease versus 33% of patients with chemosensitive disease; P = 0.005) and decreased overall patient survival (35% versus 89% 1-year survival; P = 0.02). Simultaneous blockage of the intrinsic and extrinsic pathways could be explained by a defect located at a point of convergence of the two pathways, probably related to overexpression of endogenous inhibitors of the effector-caspases, rather than decreased levels of these proteases. This study supports the importance of apoptosis pathways in determining response to chemotherapy and suggests that functional defects in caspase activation are prognostic in patients with leukemia.