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Obesity is a known and commonly encountered risk factor for the development of cardiac diseases. Patients with cardiac diseases who also have obesity do not benefit optimally from standard cardiac rehabilitation (CR) programs. Exercises performed during CR are not the best fit for patients with obesity and counselling sessions often do not address their specific needs. OPTICARE XL is the first large multicentre randomised controlled trial to investigate the added value of a dedicated one-year CR program specifically designed for patients with obesity and integrated in daily practice. The short-term effects on body weight and physical activity were promising and patients with obesity experienced the program as highly desirable. However, the OPTICARE XL CR program did not show long-term added value compared with standard CR on health-related quality of life, psychosocial well-being, body weight, physical activity and physical fitness, nor on costs. The current article offers an overview of the background of this trial and discusses the most important results of the OPTICARE XL trial and the reasons behind the unanticipated long-term outcomes. Furthermore, it offers recommendations for future research and how to redesign the OPTICARE XL CR program to expand the short-term results., (© 2023. The Author(s).)

Objective: Previously published results of the OPTICARE XL open label randomized controlled trial showed no added value of OPTICARE XL CR, a dedicated cardiac rehabilitation (CR) program for patients with obesity, with respect to health-related quality of life (primary outcome). This clinical trial studied the effects of OPTICARE XL CR on several secondary outcomes, which included body weight, physical activity, sedentary behavior, and physical fitness., Methods: Patients with coronary artery disease or atrial fibrillation and body mass index ≥ 30 were randomized to OPTICARE XL CR (n = 102) or standard CR (n = 99). OPTICARE XL CR was a 1-year group intervention, specifically designed for patients with obesity that included aerobic and strength exercise, behavioral coaching, and an aftercare program. Standard CR consisted of a 6- to 12-week group aerobic exercise program, supplemented with cardiovascular lifestyle education. Study end points included body weight, physical activity, sedentary behavior (accelerometer), and physical fitness (6-Minute Walk Test and handgrip strength), which were evaluated 6 months after the end of CR (primary endpoint) and 3 months after the start of CR., Results: Six months after completion of either program, improvements in body weight, physical activity, sedentary behavior, and physical fitness were similar between the groups. Three months after CR start, patients randomized to OPTICARE XL CR showed greater weight loss (mean change = -3.6 vs -1.8 kg) and a larger improvement in physical activity (+880 vs +481 steps per day) than patients randomized to standard CR., Conclusion: Patients allocated to OPTICARE XL CR lost significantly more body weight and showed promising results with respect to physical activity 3 months after the start of CR; however, these short-term results were not expanded or sustained in the longer term., Impact: Patients with obesity do not benefit from standard CR programs. The new OPTICARE XL CR program showed its effects in the short term on weight loss and physical activity, and, therefore, redesign of the aftercare phase is recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Objective: To identify clusters of patients according to changes in their physical behaviour during and after cardiac rehabilitation, and to predict cluster membership., Methods: The study included 533 patients (mean age 57.9 years; 18.2% females) with a recent acute coronary syndrome who participated in a 12-week multi-disciplinary cardiac rehabilitation programme, within a cohort study design. Physical behaviour (light physical activity, moderate-to vigorous physical activity, step count, and sedentary behaviour) was measured using accelerometry at 4 timepoints. To identify clusters of patients according to changes in physical behaviour during and after cardiac rehabilitation, latent class trajectory modelling was applied. Baseline factors to predict cluster membership were assessed using multinomial logistic regression., Results: During and after cardiac rehabilitation, 3 separate clusters were identified for all 4 physical behaviour outcomes: patients with steady levels (comprising 68-83% of the patients), and improving (6-21%) or deteriorating (4-23%) levels. Main predictor for membership to a specific cluster was baseline physical behaviour. Patients with higher starting physical behaviour were more likely to be a member of clusters with deteriorating levels., Conclusion: Separate clusters of physical behaviour changes during and after cardiac rehabilitation could be identified. Clusters were mainly distinguished by baseline physical behaviour level.

Background: Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control., Aims: This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event., Methods and Results: Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS. Patients aged ≥45 years at ≥6 months after coronary event were included. The SMART-REACH score was used to estimate 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events with current treatment and potential risk reduction and gains in event-free years with maximal treatment (lifestyle and pharmacological). In 3230 atherosclerotic cardiovascular disease patients (24% women), at median interquartile range (IQR) 1.1 years (1.0-1.8) after index event, 10-year risk was median (IQR) 20% (15-27%) and lifetime risk 54% (47-63%). Whereas 70% used conventional medication, 82% had ≥1 drug-modifiable risk factor not on target. Furthermore, 91% had ≥1 lifestyle-related risk factor not on target. Maximizing therapy was associated with a potential reduction of median (IQR) 10-year risk to 6% (4-8%) and of lifetime risk to 20% (15-27%) and a median (IQR) gain of 7.3 (5.4-10.4) atherosclerotic cardiovascular disease event-free years., Conclusions: Amongst patients with atherosclerotic cardiovascular disease, maximizing current, guideline-based preventive therapy has the potential to mitigate a large part of their risk of recurrent events and to add a clinically important number of event-free years to their lifetime., Competing Interests: Conflict of interest: T.T. declares to have no disclosures; M.Sn. declares to have no disclosures; S.H. has no disclosures; N.H. has no disclosures; M.Su. has no disclosures; E.M.C. has no disclosures; H.G. has no disclosures; J.D. has no disclosures; F.M. has no disclosures for this study; F.V. has no disclosures; W.S.R. has no disclosures; R.P. declares has no disclosures; H.J. received unrestricted research grants to institution from Bayer, Amgen, and Sanofi and is a member of the national advisory board Amgen (The Netherlands). These funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

We hypothesize that a novel tailor-made cardiac rehabilitation (CR) program for obesity patients (OPTICARE XL) has better outcomes as compared to usual CR regarding parameters of cardiac function as measured by conventional and advanced transthoracic echocardiography. This is an open-label, randomized controlled trial. Inclusion criteria were: patients referred to CR with a body mass index (BMI) ≥30 kg/m2, and age ≥18 years with either coronary artery disease or nonvalvular atrial fibrillation. The experimental group participated in OPTICARE XL and the controls received the usual CR. Subjects randomized to OPTICARE XL received on top of usual CR behavioural therapy for a healthy diet and an active lifestyle for the first 12 weeks. Also, the exercise program was more tailored. Furthermore, a behavioural after-care program was organized with 6 meetings between weeks 13-52. Transthoracic (speckle tracking) echocardiography was performed at baseline and one-year follow-up. A total of 42 patients completed the follow-up, 21 in both groups. There was a mild but statistically significant reduction in weight over time, however, this was comparable between groups. There was no improvement observed in any of the echocardiographic parameters. In conclusion, cardiac function in obesity patients was not improved one-year after a novel tailor-made CR program (OPTICARE XL) as compared to usual CR., (© 2023. The Author(s).)

Purpose We studied the effectiveness of a new cardiac rehabilitation (CR) program developed for patients with obesity compared with standard CR on HRQOL and psychosocial well-being. Materials and methods OPTICARE XL was a multicentre RCT in patients with cardiac disease and obesity (Netherlands Trial Register: NL5589). Patients were randomized to OPTICARE XL CR ( n  = 102) or standard CR ( n  = 99). The one-year OPTICARE XL CR group program included endurance and resistance exercises, behavioural coaching, and after-care. Standard CR consisted of a 6- to 12-week endurance exercise group program, and cardiovascular lifestyle education. Primary endpoint was HRQOL (MacNew) at six months post CR. Second, we assessed anxiety and depression (both HADS), fatigue (FSS), and participation in society (USER-P). Results In both groups, improvements in HRQOL were observed six months post CR. Mean HRQOL improved from 4.92 to 5.40 in standard CR [mean change (95% CI): 0.48 (0.28, 0.67)] and from 4.96 to 5.45 in OPTICARE XL CR (mean change (95% CI): 0.49 (0.29, 0.70), without between-group differences. Psychosocial well-being improvements within both groups were obtained at six months post CR, regardless of allocated program. Conclusions OPTICARE XL CR did not have added value in improving HRQOL and psychosocial well-being in patients with obesity.Implications for rehabilitationMore than a third of cardiac patients suffers from obesity, and standard cardiac rehabilitation (CR) programs are suboptimal in this increasing patient population.The OPTICARE XL CR program is a state-of-the art, one-year CR program designed for patients with obesity including aerobic and strength exercises, behavioural coaching towards a healthy diet and an active lifestyle, and after-care.Improvements in HRQOL and psychosocial well-being were comparable between patients with obesity allocated to standard CR and OPTICARE XL CR.Therefore, there was no additional benefit of OPTICARE XL CR.

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment. The variability caused by using different whole slide scanners has been identified as one decisive component in the underlying domain shift. The goal of the MICCAI MIDOG 2021 challenge was the creation of scanner-agnostic MF detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were provided. In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance. The winning algorithm yielded an F 1 score of 0.748 (CI95: 0.704-0.781), exceeding the performance of six experts on the same task., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest

Objectives: The primary objective was to determine the responsiveness of the Dutch version of the 13-item Tampa Scale for Kinesiophobia for cardiac patients (TSK-NL Heart). The secondary objective was to assess changes in kinesiophobia during cardiac rehabilitation., Methods: Kinesiophobia was measured pre- and post-cardiac rehabilitation using the TSK-NL Heart questionnaire in 109 cardiac patients (61 years; 76% men). The effect size of kinesiophobia score changes was calculated for the full population. A measure that is responsive to change should produce higher effects sizes in patients in whom kinesiophobia improves. Therefore, effect sizes were also calculated for patients who did or did not improve on selected external measures. For this step, the Cardiac Anxiety Questionnaire (CAQ) and the Hospital Anxiety and Depression Scale (HADS) were completed as external measures in a subsample of 58 patients., Results: The effect size of the TSK-NL Heart for the full study population was small (0.29). In line with the study hypothesis the effect size was higher (moderate) for patients with improved CAQ (0.52) and HADS scores (0.54). Prevalence of high kinesiophobia levels decreased from 40% pre-cardiac rehabilitation to 26% post-cardiac rehabilitation (p = 0.004)., Conclusion: The TSK-NL Heart has moderate responsiveness and can be used to measure changes in kinesiophobia. Improvements in kinesiophobia were observed during cardiac rehabilitation. Nevertheless, high levels of kinesiophobia were still highly prevalent post-cardiac rehabilitation.

Aims: Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre-based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness., Methods and Results: A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12-week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4-5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6-min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all-cause mortality or hospitalization., Conclusions: HF-aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: To determine differences in participation problems between diagnostic groups and to examine diagnosis as a determinant of participation with and without statistically accounting for confounders., Design: Secondary analyses of data from 8 studies., Setting: Community, the Netherlands., Participants: Participants (N=1735) in diagnostic groups: stroke (n=534), subarachnoid hemorrhage (n=104), other acquired brain injury (n=163), progressive neurologic diseases (n=112), acute coronary syndrome (n=536), and spinal cord injury (n=286)., Interventions: Not applicable., Main Outcome Measures: Participation was measured with the Utrecht Scale for Evaluation of Rehabilitation-Participation. This measure has 3 scales: Restrictions, Satisfaction, and Frequency. In this study, scores were also computed for 3 domains across these scales: Productivity, Leisure, and Social. Scores ranged from 0 (worst) up to 100 (best). Possible confounders were age, sex, level of education, marital status, and time since onset of the condition., Results: Significant differences were found in levels of participation between diagnostic groups. Individuals with acute coronary syndrome showed better participation scores in all scales and domains compared with most or all other diagnostic groups, except for the Social domain. Individuals with progressive neurologic diseases showed the lowest (worst) Restriction and Satisfaction scores, whereas those with stroke showed the lowest Frequency scores. After correcting for confounders, diagnosis explained significant proportions of the variance of participation (Frequency, 6.4%; Restrictions, 15.1%; Satisfaction, 5.1%; Productivity, 13.2%; Leisure, 13.8%; Social, 6.9%)., Conclusions: Participation problems occurred in all 6 diagnostic groups within this study. Differences were found in participation between diagnostic groups, demonstrating diagnosis-specific participation profiles, including after correcting for confounders., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to investigate the relationship between body mass index (BMI) class and physical activity and sedentary behavior in patients with acute coronary syndrome (ACS) during cardiac rehabilitation (CR)., Methods: This study was a secondary analysis of the OPTICARE trial. Physical activity and sedentary behavior were measured in participants with ACS (n = 359) using actigraphy at baseline, directly after completion of a multidisciplinary 12-week exercise-based CR program and 9 months thereafter. Outcome measures were step count and duration of time (percentage of wear time) spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior. Participants were classified as normal weight (BMI = 18.5-24.99 kg/m2; n = 82), overweight (BMI = 25.0-29.99 kg/m2; n = 182), or obese (BMI ≥ 30.0 kg/m2; n = 95). Linear mixed-effects models were applied to study the relationship between BMI class and physical activity and sedentary behavior., Results: At the start of CR, compared with participants with normal weight, participants with obesity made on average 1.11 steps fewer per minute (952 steps/d), spent 2.9% (25 min/d) less time in light physical activity, and spent 3.31% (28 min/d) more time in sedentary behavior. Participants of all BMI classes improved their physical activity and sedentary behavior levels similarly during CR, and these improvements were maintained after completion of CR., Conclusion: Participants with ACS who had obesity started CR with a less favorable physical activity and sedentary behavior profile than that of participants with normal weight. Because all BMI classes showed similar improvement during CR, this deficit was preserved., Impact: This study indicates that reconsideration of the CR program in the Netherlands for patients with ACS and obesity is warranted, and development of more inclusive interventions for specific populations is needed. A new program for people with obesity should include added counseling on increasing physical activity and preventing sedentary behavior to facilitate weight loss and reduce mortality risk., Lay Summary: People with ACS who have obesity are less active and sit more than individuals with normal weight, both during and after CR. This study suggests that CR needs to be changed to help individuals increase their physical activity to help them lose weight and reduce their risk of death., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Background: During transition to retirement there is often a rearrangement of daily life which might provide a key opportunity for interventions to promote a non-sedentary and active lifestyle. To be able to design effective interventions, it is essential to know which sedentary and physical behaviour domains (eg, at home or during leisure time) have potential to facilitate healthy ageing during the retirement transition., Objective: To determine whether unfavourable sedentary and physical activity behaviour before retirement predict unfavourable sedentary and physical activity behaviour after retirement., Design: Population-based cohort., Setting and Participants: Adults (n=3272) employed in 2010 but retired in 2014., Methods: Self-reported preretirement job activity, sedentary leisure time, physical activity at home, and walking-cycling and exercise were assessed as predictors for unfavourable sedentary and physical activity behaviours after retirement using logistic regression. Unfavourable behaviours were defined based on the respective median of the cohort distribution. Furthermore, the OR for having multiple unfavourable behaviours after retirement was determined, based on the amount of unfavourable behaviours before retirement. All models were adjusted for gender and education., Results: Unfavourable preretirement physical activity and sedentary behaviour at home or during leisure time were the strongest predictors of the same behaviours after retirement. Unfavourable job activity did not predict physical activity but did predict unfavourable sedentary behaviour after retirement (OR=1.66, 95% CI 1.41 to 1.96). Unfavourable exercise behaviour before retirement predicted unfavourable sedentary and physical activity after retirement in all domains. With all behaviours being unfavourable before retirement, the OR of having at least three unfavourable behaviours after retirement was 36.7 (95% CI 16.8 to 80.5)., Conclusions: Adults with a higher number of unfavourable preretirement physical activity and sedentary behaviours are likely to carry these unfavourable behaviours into retirement age. Interventions should target those with more unfavourable preretirement physical activity and sedentary behaviours before retirement, and those interventions focusing on exercise might have greatest potential., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To examine the strength of the association between exercise capacity and health-related quality of life (HRQOL) during and after cardiac rehabilitation (CR) in patients with acute coronary syndrome (ACS) who completed CR., Design: Prospective cohort study., Setting: Outpatient CR center., Participants: Patients (N=607) with ACS who completed CR., Interventions: Multidisciplinary 12-week exercise-based CR program., Main Outcome Measures: At baseline (pre-CR), the 6-Minute Walk Test (6MWT) was performed to determine exercise capacity, and the MacNew Heart Disease Health-related Quality of Life questionnaire was used to assess HRQOL. Measurements were repeated immediately after completion of CR (post-CR): at 12 months and 18 months follow-up. Multivariable linear regression, including an interaction term for time and exercise capacity, was applied to study the association between exercise capacity and HRQOL at different time points relative to CR, whereas model parameters were estimated by methods that accounted for dependency of repeated observations within individuals., Results: Mean age in years ± SD was 58±8.9 and 82% of participants were male. Baseline mean 6MWT distance in meters ± SD was 563±77 and median (25th-75th percentile) global HRQOL was 5.5 (4.6-6.1) points. Mean 6MWT distance (P<.001) and the global (P<.001), physical (P<.001), emotional (P<.001) and social (P<.001) domains of HRQOL improved significantly during CR and continued to improve during follow-up post-CR. Independent of the timing relative to CR (ie, pre-CR, post-CR, or during follow-up), a difference of 10 m 6MWT distance was associated with a mean difference in the global HRQOL domain of 0.007 (95% confidence interval [CI], 0.001-0.014) points (P=.029) and a mean difference in the physical domain of 0.009 (95% CI, 0.001-0.017) points (P=.023)., Conclusions: Better exercise capacity was significantly associated with higher scores on the global and physical domains of HRQOL, irrespective of the timing relative to CR, albeit these associations were weak. Hence, CR programs in secondary prevention should continue to aim at enhancing both HRQOL and exercise capacity., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: In this secondary analysis of data from the OPTICARE trial, we compared the effects of two behavioral interventions integrated into cardiac rehabilitation to standard rehabilitation with regard to functional capacity, fatigue, and participation in society., Design: This is a randomized controlled trial., Setting: This study was conducted in a cardiac rehabilitation setting., Subjects: A total of 740 patients with acute coronary syndrome were recruited for this study., Interventions: Patients were randomized to (1) three months of standard rehabilitation; (2) cardiac rehabilitation plus nine months after-care with face-to-face group lifestyle counseling; or (3) cardiac rehabilitation plus nine months after-care with individual lifestyle telephone counseling., Main Measures: Functional capacity (6-minute walk test), fatigue (Fatigue Severity Scale), and participation in society (Utrecht Scale for Evaluation of Rehabilitation-Participation) were measured at randomization, 3, 12, and 18 months., Results: Additional face-to-face sessions resulted at 12 months in 12.49 m more on the 6-minute walk test compared to standard rehabilitation ( P = .041). This difference was no longer present at 18 months. Prevalence of fatigue decreased from 30.2% at baseline to 11.9% at 18 months compared to an improvement from 37.3% to 24.9% after standard rehabilitation (between-group difference: odds ratio = 0.47; P = .010). The additional improvements in functional capacity seemed to be mediated by increases in daily physical activity. No mediating effects were found for fatigue. No additional improvements were seen for participation in society. Additional telephonic sessions did not result in additional intervention effects., Conclusion: Extending cardiac rehabilitation with a face-to-face behavioral intervention resulted in additional long-term improvements in fatigue and small improvements in functional capacity up to 12 months. A telephonic behavioral intervention provided no additional benefits.

Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2 -/- γ c -/- mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction. Higher levels of infiltrating B-cells were observed in various organs of mice depleted for macrophages. With (early) B-cell depletion using Rituximab, a clear improvement on clinical symptoms was observed, even when probably only inactivated B-cells were deleted. However, the histological examinations only showed a significant morphological effect on liver fibrosis. This may be related to a difference in the mRNA levels of TGF- β . Also, lower mRNA levels of Tregs in some organs were observed after Rituximab treatment, which contradicts that a higher number of Tregs would always be related to less severe GvHD. Our data show that both macrophage depletion and (early) B-cell depletion in a xenogeneic mouse model can influence the clinical, histological, and cytokine production of a GvHD response.

Competing Interests: The authors have no conflicts of interest to declare.

Aims: We aimed to assess the effects of a multidisciplinary cardiac rehabilitation (CR) program on survival after treatment with primary percutaneous coronary intervention (pPCI) for acute coronary syndrome (ACS)., Methods and Results: Using propensity matching analysis, a total of 1159 patients undergoing CR were 1:1 matched with ACS patients who did not undergo CR and survived at least 60 days. The Kaplan-Meier analyses and multivariate Cox regression analysis were applied to study differences in survival. During follow-up, a total of 335 (14.5%) patients had died. Cumulative mortality rates at 5 and 10 years were 6.4% and 14.7% after CR and 10.4% and 23.5% in the no CR group (P < 0.001). Cardiac rehabilitation patients had 39% lower mortality than non-CR controls [10-year mortality 14.7% vs. 23.5%; adjusted hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.46-0.81]. A total of 915 (78.9%) patients completed CR and had 46% lower mortality than those who did not complete CR (10-year mortality 13.6% vs. 18.9%; adjusted HR 0.54; 95% CI 0.42-0.70)., Conclusion: Patients who underwent pPCI for ACS, with a CR program had lower mortality than their non-CR counterparts. Mortality was particularly low in patients who completed the program. In conclusion, CR is still beneficial in terms of survival.

Background: Standard cardiac rehabilitation (CR) is insufficient to help patients achieve an active lifestyle. The effects of two advanced and extended behavioral CR interventions on physical activity (PA) and sedentary behavior (SB) were assessed., Methods: In total, 731 patients with ACS were randomized to 1) 3months of standard CR (CR-only); 2) 3months of standard CR with three pedometer-based, face-to-face PA group counseling sessions followed by 9months of aftercare with three general lifestyle, face-to-face group counseling sessions (CR+F); or 3) 3months of standard CR, followed by 9months of aftercare with five to six general lifestyle, telephonic counseling sessions (CR+T). An accelerometer recorded PA and SB at randomization, 3months, 12months, and 18months., Results: The CR+F group did not improve their moderate-to-vigorous intensity PA (MVPA) or SB time compared to CR-only (between-group difference=0.24% MVPA, P=0.349; and 0.39% SB, P=0.529). However, step count (between-group difference=513 steps/day, P=0.021) and time in prolonged MVPA (OR=2.14, P=0.054) improved at 3months as compared to CR-only. The improvement in prolonged MVPA was maintained at 18months (OR=1.91, P=0.033). The CR+T group did not improve PA or SB compared to CR-only., Conclusions: Adding three pedometer-based, face-to-face group PA counseling sessions to standard CR increased daily step count and time in prolonged MVPA. The latter persisted at 18months. A telephonic after-care program did not improve PA or SB. Although after-care should be optimized to improve long-term adherence, face-to-face group counseling with objective PA feedback should be added to standard CR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The OPTICARE (OPTImal CArdiac REhabilitation) randomised controlled trial compared two advanced and extended cardiac rehabilitation (CR) programmes to standard CR for patients with acute coronary syndrome (ACS). These programmes were designed to stimulate permanent adoption of a heart-healthy lifestyle. The primary outcome was the SCORE (Systematic COronary Risk Evaluation) 10-year cardiovascular mortality risk function at 18 months follow-up., Methods: In total, 914 patients with ACS (age, 57 years; 81% men) were randomised to: (1) 3 months standard CR (CR-only); (2) standard CR including three additional face-to-face active lifestyle counselling sessions and extended with three group fitness training and general lifestyle counselling sessions in the first 9 months after standard CR (CR+F); or (3) standard CR extended for 9 months with five to six telephone general lifestyle counselling sessions (CR+T)., Results: In an intention-to-treat analysis, we found no difference in the SCORE risk function at 18 months between CR+F and CR-only (3.30% vs 3.47%; p=0.48), or CR+T and CR-only (3.02% vs 3.47%; p=0.39). In a per-protocol analysis, two of three modifiable SCORE parameters favoured CR+F over CR-only: current smoking (13.4% vs 21.3%; p<0.001) and total cholesterol (3.9 vs 4.3 mmol/L; p<0.001). The smoking rate was also lower in CR+T compared with the CR-only (12.9% vs 21.3%; p<0.05)., Conclusions: Extending CR with extra behavioural counselling (group sessions or individual telephone sessions) does not confer additional benefits with respect to SCORE parameters. Patients largely reach target levels for modifiable risk factors with few hospital readmissions already following standard CR., Trial Registration Number: ClinicalTrials.gov NCT01395095; results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: The association between body mass index (BMI) and subjective health status before and after cardiac rehabilitation (CR) and 1 year later was compared in patients undergoing primary percutaneous coronary intervention (pPCI) who did (CR group) and did not receive CR (no-CR group). The aim was to investigate the association between BMI and subjective health status based on the Short Form-12 questionnaire., Methods: Between 2009 and 2011, 242 patients with pPCI with an acute myocardial infarction completed a CR program and were compared with 115 patients in the no-CR group. All patients completed the Short Form-12 questionnaire at baseline, at 12 weeks, and at 1-year followup. The CR program consisted of a 2 sessions per week for 1.5 hours each for 12 weeks. Patients were categorized into 3 groups based on BMI: normal weight, overweight, and obese., Results: Compared with patients in the no-CR group, CR group patients in the overweight group significantly improved their subjective health status after CR and these improvements were sustained at 1-year followup. CR patients in the normal weight and obese groups did not significantly improve subjective health status. The overweight patients had the highest improvement in subjective health status (OR = 3.4 post-CR and 5.1 at 1 year of followup)., Conclusions: After CR, overweight patients showed the best improvement in subjective health status. CR did not significantly improve subjective health status in normal-weight and obese patients.

Objective: To objectively measure changes in both moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) during and after standard cardiac rehabilitation (CR)., Design: Prospective cohort study., Setting: Outpatient CR center., Participants: Patients (N=135) with acute coronary syndrome (ACS) who completed CR., Interventions: Multidisciplinary CR according to current guidelines., Main Outcome Measures: The proportion of time spent in MVPA and SB was objectively measured with an accelerometer. The distribution of time in MVPA and SB was also determined (eg, average length of time periods spent in MVPA and SB). All measurements were obtained before CR, after CR, and at 1-year follow-up., Results: Patients' time in MVPA during waking hours increased by .65% (≈5min) during CR (P=.002) and remained increased at 1-year follow-up (P=.037). The MVPA distribution did not change. During CR, time spent in SB decreased by 2.49% (≈22min; P<.001), and SB time became more fragmented with more breaks and shorter SB periods (P<.001). These SB improvements were maintained at 1-year follow-up (P<.001)., Conclusions: Patients with ACS achieved a small improvement in MVPA time during CR, but MVPA distribution remained unchanged. More substantial improvements occurred for SB time and distribution. However, by the end of CR, patients still spent relatively little time in MVPA and a long time in SB, which is known to be detrimental to cardiovascular health. Although CR programs have the potential to improve physical behavior, our findings highlight the need to develop adjusted CR targets that address the amount and distribution of MVPA and SB., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Medullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC., Methods: All patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were included. A tissue microarray was constructed in which 111 primary tumors could be analyzed for expression of HIF-1α, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic variables and survival., Results: The mean age of patients was 46.3 years (SD 15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF-1α negative and 62 (55.9%) were HIF-1α positive. Positive HIF-1α expression was an independent negative indicator for progression free survival (PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 - 7.3). Five-years survival decreased from 94.0% to 65.9% for the HIF-1α positive group (p=0.007). Even within the group of patients with TNM-stage IV disease, HIF-1α positivity was associated with a worse prognosis, shown by a decrease in 5-years survival of 88.0% to 49.3% (p=0.020)., Conclusion: Expression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.

Background: Cardiac rehabilitation (CR) is recommended as secondary prevention in primary percutaneous coronary intervention (pPCI) patients. This study was conducted to expand the knowledge about age-effects of CR in pPCI patients. The aim of this study was to compare changes in subjective health status (SHS) during and after CR between patients <60years and patients ≥60years, who underwent pPCI after myocardial infarction., Methods: Between 2009 and 2011, in total 282 pPCI patients who participated in CR were included. Patients completed the Short Form 12 (SF-12) questionnaire at baseline (pre-CR), 3months (post-CR) and 12months follow-up. Patients were divided into two age-groups, <60years versus ≥60years. To compare improvements in SHS between groups, Generalized Estimating Equations (GEE) analyses were performed., Results: The mean physical component summary (PCS) score improved over time in both groups and even reached mean levels of the normative Dutch population. The improvement on the PCS score was equal in both age groups. The mental component summary (MCS) score also improved in both groups. Patients <60years reported on average more improvement on the MCS score than patients ≥60years (Exp(B) 1.019; 95%CI 1.009-1.030; P<0.001). However, mean levels of the normative Dutch population were not reached by patients <60years., Conclusion: Even though pPCI patients <60years reported more improvement on the MCS score, mean levels of the normative Dutch population were not reached. Therefore, a tailored CR program with more focus on their mental status, may be beneficial in younger patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive. We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization. Data were coupled to clinical variables and treatment history. ERα, PR and AR receptor status converted from positive in the primary tumor to negative in the effusion metastases or vice versa in 25-30%, 30-35% and 46-51% of cases for the 1% and 10% thresholds for positivity, respectively. 19-25% of patients converted clinically relevant from "ER α + or PR+" to ER α -/PR- and 3-4% from ER α -/PR- to "ERα+ or PR+". For HER2, conversion was observed in 6% of cases. Importantly, receptor conversion for ERα ( p = 0.058) and AR ( p < 0.001) was more often seen in patients adjuvantly treated with endocrine therapy. Analogous to this observation, HER2-loss was more frequent in patients adjuvantly treated with trastuzumab ( p < 0.001). Alike solid distant metastases, receptor conversion for ERα, PR, AR and HER2 is a frequent phenomenon in peritoneal and pleural effusion metastases. Adjuvant endocrine and trastuzumab therapy imposes an evolutionary selection pressure on the tumor, leading to receptor loss in effusion metastases. Determination of receptor status in malignant effusion specimens will facilitate endocrine treatment decision-making at this lethal state of the disease, and is hence recommended whenever possible., Competing Interests: CONFLICTS OF INTEREST This manuscript has neither been published, nor is currently under revision elsewhere and none of the authors has a conflict of interest.

Background: APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated., Patients and Methods: RNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20) and distant metastases (N = 35). APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1) status., Results: Overall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23). Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002). However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028)., Conclusion: APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer., Competing Interests: Our commercial funding does not alter our adherence to PLOS ONE policies on sharing data and materials.

Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double-knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or δ-catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors., Competing Interests: Compliance with Ethical Standards Grants Research was supported by grants from the Netherlands Organization for Scientific Research (NWO/ZonMW-VIDI 016.096.318), Foundation Vrienden UMC Utrecht (11.081) and the Dutch Cancer Society (KWF-UU-2011-5230). Conflict of Interest The authors declare that they have no conflict of interest.

Background: Low marital quality is associated with adverse health outcomes and lower personal well-being. Loneliness increases the risk of cardiovascular disease and mortality and predicts poor quality of life. The aim of this study was to investigate the association between marital quality and loneliness and subjective health status in primary percutaneous coronary intervention (pPCI) patients who underwent cardiac rehabilitation (CR)., Design/methods: In a prospective cohort study, pPCI patients that followed CR were included between 2009-2011. A total of 223 patients responded to the Short Form 12 (SF-12) (subjective health status), Maudsley Marital Questionnaire (MMQ-6) (marital quality) and University of California, Los Angeles - Revised (UCLA-R) questionnaires at baseline (pre-CR) and at three months (post-CR) or at 12 months follow-up. Subjective health status is displayed by a physical component summary (PCS) score and a mental component summary (MCS) score. Generalized estimating equation (GEE) analyses were performed to test improvements in subjective health status., Results: Changes over time in subjective health status scores were similar between patients with optimal marital quality vs patients with less optimal marital quality and non-lonely patients vs lonely patients. The MCS level at one-year follow-up of both patients with less optimal marital quality and lonely patients was lower compared with a healthy Dutch population (respectively; mean MCS score 47.3 (standard deviation (SD) 10.5); p = 0.013 and mean MCS score 46.1 (SD 11.2); p = 0.010)., Conclusion: Both patients with less optimal marital quality and lonely patients did not reach the MCS level of a healthy Dutch population. Therefore, extra care and support should be given to these patients in a CR programme., (© The European Society of Cardiology 2016.)

Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1, and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objectives: To assess changes in participation in society (frequency, restrictions, satisfaction) during and after cardiac rehabilitation (CR) and to assess associations between participation and heath-related quality of life (HRQOL)., Design: Prospective cohort study., Setting: Outpatient CR center., Participants: Patients with coronary artery disease (N=121; mean age, 57y; 96 men [79%])., Interventions: Multidisciplinary CR., Main Outcome Measures: Participation in society was assessed with the Utrecht Scale for Evaluation of Rehabilitation-Participation and HRQOL with the MacNew Heart Disease health-related quality of life questionnaire. All measurements were performed pre-CR, post-CR, and 1 year after the start of CR., Results: Frequency of participation did not change during and after CR. The proportion of patients experiencing restrictions in participation decreased from 69% pre-CR to 40% post-CR (P<.001) and 29% at 1 year (P<.001 vs post-CR). Pre-CR, 71% of patients were dissatisfied with their participation. This improved to 49% post-CR (P<.001) and 53% at 1 year (P<.001 vs pre-CR). Experienced restrictions explained 5% to 7% of the improvement in HRQOL during CR and satisfaction with participation explained 10% to 19%., Conclusions: Participation in society improves in patients undergoing CR. Despite these improvements, the presence of coronary artery disease is associated with persistent restrictions and dissatisfaction with participation. Because experienced restrictions and dissatisfaction are related to changes in HRQOL it is important to address these aspects of participation during CR., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate fatigue during and after a multidisciplinary cardiac rehabilitation programme and its association with aerobic capacity., Design: Longitudinal cohort study., Patients: A total of 121 patients with coronary artery disease (79% men), mean age 57 years., Methods: Fatigue was measured with the Fatigue Severity Scale (FSS) and aerobic capacity with the 6-min walk test (6MWT). FSS scores ≥ 4 were defined as fatigue and >5.1 as severe fatigue. Measurements were taken before (T0) and after rehabilitation (T1) and at 1-year follow-up (T2)., Results: Fatigue decreased from 3.49 at baseline to 3.03 post-rehabilitation (p=0.002) and decreased further to 2.75 at follow-up (p<0.001 vs T0). At baseline, 17.7% of patients were classified as severely fatigued. After cardiac rehabilitation, the prevalence decreased to 10.6% (p<0.001) and to 8.1% at follow-up (p=0.011 vs T0). Although the prevalence of severely fatigued patients decreased, it was still high compared with healthy individuals (3.5%). Aerobic capacity was weakly associated with a reduction in fatigue (p=0.030)., Conclusion: Fatigue decreased during and after cardiac rehabilitation. However, the prevalence of severely fatigued patients remained high after cardiac rehabilitation. Fatigue should be identified at an early stage in order to provide additional programmes aiming to reduce severe fatigue.

Background: Optimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR)., Purpose: The purpose of this study was to systematically review literature regarding short-term effects (<6 months after completion of CR) and long-term effects (≥6 months after completion) of standard CR on physical activity levels in patients with ACS., Data Sources: PubMed, EMBASE, CINAHL, and PEDro were systematically searched for relevant randomized clinical trials (RCTs) published from 1990 until 2012., Study Selection: Randomized clinical trials investigating CR for patients with ACS reporting physical activity level were reviewed., Data Extraction: Two reviewers independently selected articles, extracted data, and assessed methodological quality. Results were summarized with a best evidence synthesis. Results were categorized as: (1) center-based/home-based CR versus no intervention, (2) comparison of different durations of CR, and (3) comparison of 2 types of CR., Data Synthesis: A total of 26 RCTs were included. Compared with no intervention, there was, at most, conflicting evidence for center-based CR and moderate evidence for home-based CR for short-term effectiveness. Limited evidence and no evidence were found for long-term maintenance for center-based and home-based CR, respectively. When directly compared with center-based CR, moderate evidence showed that home-based CR has better long-term effects. There was no clear evidence that increasing training volume, extending duration of CR, or adding an extra intervention to CR is more effective., Limitations: Because of the variety of CR interventions in the included RCTs and the variety of outcome measures in the included RCTs, pooling of data was not possible. Therefore, a best evidence synthesis was used., Conclusions: It would appear that center-based CR is not sufficient to improve and maintain physical activity habits. Home-based programs might be more successful, but the literature on these programs is limited. More research on finding successful interventions to improve activity habits is needed., (© 2015 American Physical Therapy Association.)

Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host-induced fibrotic response in xenogeneic RAG2(-/-)γc(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Because formaldehyde is toxic and creates cross-links that may hinder immunohistochemical studies, we tested 3 new cross-linking (F-Solv [Adamas, Rhenen, the Netherlands]) and non-cross-linking (FineFIX [Milestone, Bergamo, Italy] and RCL2 [Alphelys, Plaisir, France]) alcohol-based fixatives for routine staining in comparison with neutral buffered formalin (NBF) as the "gold standard." Fresh tissue samples were divided into 4 equal pieces and fixed in all fixatives for varying times. After paraffin embedding, H&E staining, 7 common histochemical stains, and 9 common immunohistochemical stains were performed. RCL2 fixation resulted in soft and slippery tissue, causing sectioning difficulties. F-Solv and FineFIX led to partial tissue disintegration during fixation. F-Solv performed morphologically similar to NBF but needed considerable protocol adjustments before being applicable in daily histologic and immunohistochemical practice. FineFIX did not necessitate major protocol changes but caused shrinkage artifacts, degranulation, and lysis of RBCs. RCL2 generated morphologically overall good results without major protocol changes but caused pigment deposition, degranulation, and RBC lysis. The alcohol-based fixatives had positive and negative attributes and environmental drawbacks, and none was overall comparable to NBF with regard to macroscopy, morphologic evaluation, and immunohistochemical studies.

Two common impairments in patients after stroke are loss of balance control and fatigue. We propose that both could be inter-related. The purpose of this study was to investigate the metabolic energy demand for balance control in patients after stroke during upright standing. Ten stroke patients and 12 able-bodied controls performed four 5-min upright standing tasks on a force plate; unperturbed (SU), blindfolded (SUB), on foam surface (SUF) and with feet parallel against each other (SUP). Metabolic energy expenditure, posturography measures and muscle activity (EMG) of lower leg muscles were measured. Patients required on average 125% (33Jkg(-1)s(-1)) more metabolic energy for upright standing under the various conditions than controls. In addition, balance manipulation significantly (p<0.05) affected energy expenditure (21% higher in SUB, 52% in SUF, 40% in SUP compared to SU). Although the increase in energy expenditure was on average twice as high in patients than controls no significant group by condition interaction effect was found. Overall correlations between posturography measures, EMG and energy expenditure (r=0.33-0.60) were significant (p<0.001). We conclude that impaired balance control puts an extra demand on the energy expenditure during motor activities in stroke patients. This should be considered when prescribing interventions aimed at reducing physiological strain., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: While various body weight supported locomotor training (BWSLT) approaches are reported in the literature for individuals with spinal cord injury (SCI), none have evaluated outcomes in terms of gait quality. The purpose of this study was to compare changes in measures of gait quality associated with four different BWSLT approaches in individuals with chronic motor-incomplete SCI, and to identify how gait parameters differed from those of non-disabled (ND) individuals., Methods: Data were analyzed from 51 subjects with SCI who had been randomized into one of four BWSLT groups: treadmill with manual assistance (TM), treadmill with electrical stimulation (TS), overground with electrical stimulation (OG), treadmill with locomotor robot (LR). Subjects with SCI performed a 10-meter kinematic walk test before and after 12 weeks of training. Ten ND subjects performed the test under three conditions: walking at preferred speed, at speed comparable to subjects with SCI, and with a walker at comparable speed. Six kinematic gait quality parameters were calculated including: cadence, step length, stride length, symmetry index, intralimb coordination, and timing of knee extension., Results: In subjects with SCI, all training approaches were associated with improvements in gait quality. After training, subjects with SCI walked at higher cadence and had longer step and stride lengths. No significant differences were found among training groups, however there was an interaction effect indicating that step and stride length improved least in the LR group. Compared to when walking at preferred speed, gait quality of ND subjects was significantly different when walking at speeds comparable to those of the subjects with SCI (both with and without a walker). Post training, gait quality measures of subjects with SCI were more similar to those of ND subjects., Conclusion: BWSLT leads to improvements in gait quality (values closer to ND subjects) regardless of training approach. We hypothesize that the smaller changes in the LR group were due to the passive settings used for the robotic device. Compared to walking at preferred speed, gait quality values of ND individuals walking at a slower speed and while using a walker were more similar to those of individuals with SCI.