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Purpose. Only one-third of patients with breast cancer reach the recommended activity level of 15 to 25 MET h/wk. The aim of this study was to determine the influence of personalized exercise recommendations during rehabilitation on patients’ physical activity level, fatigue, and self-perceived cognitive function as well as on side effect–associated biomarkers. Methods. Total metabolic rate, physical activity level, mean MET and steps, fatigue, self-perceived cognitive functioning , and biomarkers (C-reactive protein [CRP], interleukin 6, macrophage migration inhibiting factor [MIF], tumor necrosis factor [TNF]-α, brain-derived neurotrophic factor [BDNF], insulin-like growth factor 1 [IGF1]) were assessed in 60 patients with breast cancer in the aftercare phase before ( t0) and 8 months after ( t1) the intervention. The rehabilitation program consisted of an initial 3-week period and a 1-week stay after 4 months. Results. Paired t-test indicated a statistically significant increase in all activity outcomes from t0 to t1. Patients’ mean activity level significantly increased from 14.89 to 17.88 MET h/wk. Fatigue and self-perceived cognitive functioning significantly improved from t0 to t1. CRP levels significantly decreased, and BDNF as well as IGF1 levels significantly increased over time. Correlation analysis revealed statistically significant negative associations between fatigue, physical activity, and markers of inflammation (TNF-α and MIF). Furthermore, significant positive correlations between subjective cognitive functioning and all dimensions of fatigue were observed. Conclusions. The results support the importance of personalized exercise recommendations to increase physical activity levels in patients with breast cancer. Furthermore, the results highlighti an association between physical activity, fatigue, and inflammation.

Background The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS. Methods In this two-armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0–4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6. Discussion To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology. Trial registration DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform.

With great interest, we have read the current publication of Herrstedt et al. [1], investigating the influence of a chemotherapy-accompanying supervised exercise program on the kynurenine pathway a...

BACKGROUND: Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS.METHODS: A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0-6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their maximum heart rate (HRmax) followed by active breaks of unloaded pedalling (60% HRmax) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HRmax. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T0) and after (T3) the 3-week exercise intervention program. Blood samples of T0 will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T1) and three hours (T2) after the first exercise session of each group.DISCUSSION: This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS.TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov ( NCT03652519 ; 29 August 2018).

Background: Acute aerobic exercise leads to positive physiological adaptations within the central nervous system. These findings inspired research on potential cognitive benefits following acute aerobic exercise. The effects of acute aerobic exercise on subsequent cognitive performance, by far, have been the most researched for interference control, a subcomponent of executive function. The results of primary studies on the effects of acute aerobic exercise on subsequent interference control performance are inconsistent. Therefore, we used meta-analytic methods to pool available effect sizes, and to identify covariates that determine the magnitude of exercise-induced interference control benefits. Methods: Medline, PsycINFO, and SPORTDiscus were searched for eligible records. Hedges' g corrected standardized mean difference values (SMDs) were used for analyses. Random-effects weights were used to pool effect sizes. Moderator analyses were conducted using meta-regressions and subgroups analyses. Covariates that were here tested for moderation included parameters of the applied exercise regimen (exercise intensity and exercise duration), characteristics of examined participants (age and fitness), and methodological features of existing research (type of control group, familiarization with test procedure, type of test variable, delay between exercise cessation, and testing). Results: Fifty studies, with data from 2,366 participants, were included in qualitative and quantitative synthesis. A small, significant beneficial effect of acute aerobic exercise on time-dependent measures of interference control was revealed (k = 49, Hedges' g = −0.26, 95%CI: −34 to −0.18). Effect sizes from time-dependent measures of interference control varied widely and heterogeneity reached statistical significance (T2 = 0.0557, I2 = 28.8%). Moderator analyses revealed that higher exercise intensities (vigorous intensity and high-intensity interval training), also participants at younger or older age, and participants who are familiar with the testing procedure prior to the experiment, benefitted most from acute aerobic exercise. However, noticeable heterogeneity remained unexplained within specific subgroups (high-intensity interval training, preadolescent children, and active and supervised control group). Conclusion: Acute aerobic exercise improves subsequent interference control performance. However, the covariates exercise intensity, participants' age, and familiarization with testing procedure determine the magnitude of that effect. Methodological features were not found to influence the magnitude of effects. This dismisses some doubts that exercise induced benefits for interference control performance are scientific artifacts. The fact that large heterogeneity remained unexplained in some subgroups indicates the need for further research on covariates within these subgroups. It should be noted that effect sizes for all analyses were small. © Copyright © 2019 Oberste, Javelle, Sharma, Joisten, Walzik, Bloch and Zimmer.

Purpose Cognitive impairment is a common symptom of multiple sclerosis (MS). Physical exercise represents a promising non-pharmacological therapy option, however, potential predictors for successful cognitive improvements mediated by exercise remain to be elucidated in order to optimize targeted exercise training regimens. One of the most promising exercise training regime in this context is high-intensity interval training (HIIT). Against this backdrop, this study i) analysed the effects of a three-week HIIT compared to moderate continuous exercise on cognitive performance and ii) investigated potential predictors for changes of cognitive performance following a three-week aerobic exercise intervention. Methods Datasets of two randomized controlled trials (RCT) were pooled, resulting in a total sample size of n = 130 persons with MS (pwMS) who either performed HIIT or moderate intensity continuous (MCT) exercise 3–5x/ week for three weeks. Cognitive performance was assessed with the Brief International Cognitive Assessment for MS. I) Potential within (time) and interaction (time x group) effects for cognitive performance were investigated with univariate analyses of covariance (ANCOVA). II) Potential predictors for changes of cognitive performance were assessed by multiple linear regression models. Results ANCOVA revealed significant time effects for all cognitive outcomes and a time x group interaction for verbal learning (p=.045), with HIIT inducing superior effects compared to moderate continuous exercise (MCT). Cognitive status (impaired/intact cognition) (p= .008) and exercise regime (HIIT/moderate continuous) (p=.040) influenced changes of verbal learning. Cognitive status (p=.006) and EDSS (p=.048) affected changes of visuospatial memory in pwMS. The models accounted for 5.4% and 7.7% of the variance. Conclusion Cognitive status, exercise regime and EDSS potentially impact changes of specific cognitive domains following aerobic exercise. Further predictors for changes of cognitive performance following an aerobic exercise intervention need to be investigated as current results accounted only for a limited amount of variance. RCTs that investigate effects of physical exercise on cognitive performance should include only pwMS with impaired baseline cognitive performance. To better understand the impact of exercise on cognitive performance, it is furthermore recommendable to include cognitive assessments in clinical routine.

ObjectiveTo examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).MethodsSixty-nine pwMS (Expanded Disability Status Scale score 3.0–6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention.ResultsAcute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT.ConclusionFuture studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS.Classification of EvidenceThis study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS.Trial Registration InformationClinical trial registration number: NCT03652519.

Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

The kynurenine (KYN) pathway gains growing research interest concerning the genesis, progression and therapy of solid tumors. Previous studies showed exercise-induced effects on metabolite levels along the KYN pathway. Modulations of the KYN pathway might be involved in the positive impact of exercise on prostate cancer progression and mortality. The objective of this trial was to investigate whether a single-physical exercise alters tryptophan (TRP) metabolism and related inflammatory markers in this population. We conducted a randomized controlled trial with 24 patients suffering from prostate cancer. While the control group remained inactive, the intervention group performed a 30-min aerobic exercise on a bicycle ergometer at 75% of individual VO2peak. Before (t0) and directly after the exercise intervention (t1) KYN, TRP, kynurenic acid, quinolinic acid as well as various inflammation markers (IL6, TNF-&alpha, TGF-&beta, ) were measured in blood serum. At baseline, the present sample showed robust correlations between TRP, KYN, quinolinic acid and inflammatory markers. Regarding the exercise intervention, interaction effects for TRP, the KYN/TRP ratio and TGF-&beta, were observed. The results show for the first time that acute physical exercise impacts TRP metabolism in prostate cancer patients. Moreover, baseline associations underline the relationship between inflammation and the KYN pathway in prostate cancer.

Emerging evidence highlights the substantial role of the kynurenine pathway in various physiological systems and pathological conditions. Physical exercise has been shown to impact the kynurenine pathway in response to both single (acute) and multiple (chronic) exercise training stimuli. In this perspective article, we briefly outline the current knowledge concerning exercise-induced modulations of the kynurenine pathway and discuss underlying mechanisms. Furthermore, we expose the potential involvement of exercise-induced kynurenine pathway modulations on energy homeostasis (eg, through de novo synthesis of NAD+) and finally suggest how these modulations may contribute to exercise-induced benefits in the prevention and treatment of chronic diseases.

Background Up to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients’ self-perceived cognitive functioning and common cancer related side-effects, will be explored. Methods A single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients’ first-line chemotherapy treatment typically lasting 12–18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients’ change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance). Discussion This study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients. Trial registration DRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390, Registered on 17 January 2018. Electronic supplementary material The online version of this article (10.1186/s12885-018-4992-3) contains supplementary material, which is available to authorized users.

Disturbances in Tryptophan metabolism play a crucial role in multiple sclerosis (MS). Exercise is suspected to counteract the progress of MS and its side effects. Current research suggests alterations of Tryptophan metabolism in healthy individuals in response to exercise. We investigated the influence of acute aerobic exercise and training on Tryptophan metabolism in 57 inpatients with relapsing remitting ((RRMS) n=33) and secondary progressive ((SPMS) n=24) MS. Serotonin increased after training, whereas the kynurenine pathway was only activated in persons with RRMS. Further research is warranted to investigate whether these changes are associated with clinical measures (e.g. depressions and immune function).