Decline in Smartphone-Assessed Physical Activity Level is Associated With Clinical Outcomes in Phase I/II Clinical Cancer Trials.

BACKGROUND: A decline in physical function may be an early predictor for complications of cancer treatment. This study examined whether repeated objective smartphone measurements of physical activity and exercise capacity in patients with cancer are feasible during early-phase clinical trials (EPCTs) and whether a decline in physical function is associated with clinical outcomes. METHODS: Physical activity (steps/day) and exercise capacity (6-minute walk test [6MWT]) were measured with a smartphone before EPCT start (T0) and after 4 weeks (T1) and 8 weeks (T2). Univariable logistic regression analyzed associations between a decline in step count (≥20%), 6MWT distance (≥10%), or deterioration of ECOG performance status (PS) and trial discontinuation at 8 weeks and 90 days. Cox proportional hazards models were used to examine associations with progression-free survival (PFS) and overall survival (OS), adjusting for trial phase (I vs II), cancer type (hematologic malignancy vs solid tumor), and PS (0 vs ≥1). RESULTS: Among 117 included patients, valid step count and 6MWT measurements were available for 96.6% and 76.7% of patients at T0, 74.4% and 53.3% at T1, and 89.7% and 54.4% at T2, respectively. Patients experiencing step count decline between T0 and T1 had higher odds of trial discontinuation at 8 weeks (odds ratio, 8.67; 95% CI, 1.94-61.43), and decline between T1 and T2 was associated with discontinuation at 90 days (odds ratio, 5.20; 95% CI, 1.43-21.14). Step count decline was significantly associated with shorter PFS (hazard ratio, 3.54; 95% CI, 2.06-6.08) and OS (hazard ratio, 2.31; 95% CI, 1.26-4.23). Declines in 6MWT distance or deterioration in ECOG PS were not associated with trial discontinuation or survival. CONCLUSIONS: Repeated smartphone measurements of physical activity are feasible in patients participating in EPCTs. Additionally, physical activity decline is significantly associated with trial discontinuation, PFS, and OS. Hence, we envision that objective smartphone measurements of physical activity will contribute to optimal treatment development for patients with cancer.

Potential mechanisms underlying the effect of walking exercise on cancer-related fatigue in cancer survivors.

PURPOSE: Cancer-related fatigue (CRF) is a common and debilitating long-term side effect of cancer and its treatment. While exercise has been shown to effectively reduce CRF, the underlying mechanisms are not fully clear. Therefore, the aim of this study was to explore the effects of a 4-month walking exercise program on fatigue severity and to explore potential underlying physiological, behavioral, and psychological mechanisms of action. METHODS: We included 27 cancer survivors (59 ± 15 years, 37% female) with variable cancer diagnoses who were at least moderately fatigued and finished treatment between 6 and 36 months ago. This study with a quasi-experimental interrupted time-series design compared a 4-month walking intervention period with a 4-month control period. Measurements of fatigue and physiological, behavioral, and psychological factors were performed, supplemented with participants' perceptions on how exercise influenced their fatigue. RESULTS: A significant and clinically relevant decrease in fatigue severity was found over time (ß = - 8.1, 95% CI = - 12.1; - 4.2), but could not be attributed directly to the walking exercise intervention. Increases in muscle strength (ß = - 0.07, 95% CI = - 0.12; - 0.02), physical activity (ß = - 0.1, 95% CI = - 0.2; - 0.04), and sleep quality (ß = 1.1, 95% CI = 0.3; 1.9), as well as decreases in muscle relaxation times (ß = 0.09, 95% CI = 0.02; 0.16) and psychological distress (ß = 1.1, 95% CI = 0.8; 1.3) were associated with reductions in fatigue severity. Resilience and physical well-being were perceived as most important constructs explaining the walking exercise effects on fatigue. CONCLUSION: Our findings reveal potential physiological, behavioral, and psychological mechanisms underlying the multidimensional effects of exercise on fatigue severity. IMPLICATIONS FOR CANCER SURVIVORS: Incorporating resistance exercise and addressing resilience and physical well-being might improve the efficacy of exercise interventions for cancer survivors.

Identification of neutrophil phenotype categories in geriatric hip fracture patients aids in personalized medicine.

Objectives: The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients. This pilot study investigated the feasibility and clinical value of neutrophil phenotype analysis in geriatric patients with a hip fracture. Methods: A prospective study was conducted in a regional teaching hospital in the Netherlands. At the emergency department, blood samples were collected from geriatric patients with a hip fracture and analyzed using automated flow cytometry. Flow cytometry data were processed using an automated clustering algorithm. Neutrophil activation data were compared with a healthy control cohort. Neutrophil phenotype categories were assessed based on two-dimensional visual assessment of CD16/CD62L expression. Results: Blood samples from 45 geriatric patients with a hip fracture were included. Neutrophils showed an increased activation profile and decreased responsiveness to formyl peptides when compared to healthy controls. The neutrophil phenotype of all patients was categorized. The incidence of severe adverse outcome was significantly different between the different categories (P = 0.0331). Moreover, patients with neutrophil phenotype category 0 developed no severe adverse outcomes. Conclusions: Using point-of-care fully automated flow cytometry to analyze the neutrophil compartment in geriatric hip fracture patients is feasible and holds clinical value in determining patients at risk for adverse outcome. This study is a first step toward immuno-based precision medicine for identifying geriatric hip fracture patients that are deemed fit for surgery.

Mitochondrial complex III activity: from invasive muscle biopsies to patient-friendly buccal swab analysis.

Drug-induced mitochondrial dysfunction is a common adverse effect, particularly in case of statins-the most prescribed drugs worldwide. These drugs have been shown to inhibit complex III (CIII) of the mitochondrial oxidative phosphorylation process, which is related to muscle pain. As muscle pain is the most common complaint of statin users, it is crucial to distinguish it from other causes of myalgia to prevent unnecessary cessation of drug therapy. However, diagnosing CIII inhibition currently requires muscle biopsies, which are invasive and not practical for routine testing. Less invasive alternatives for measurement of mitochondrial complex activities are only available yet for complex I and IV. Here, we describe a non-invasive spectrophotometric method to determine CIII catalytic activities using buccal swabs, which we validated in a cohort of statin and non-statin users. Our data indicate that CIII can be reliably measured in buccal swabs, as evidenced by reproducible results above the detection limit. Further validation on a large-scale clinical setting is recommended.

Changes in Fat-Free Mass, Protein Intake and Habitual Physical Activity Following Roux-en-Y Gastric Bypass Surgery: A Prospective Study.

PURPOSE: Large inter-individual variations in post-bariatric fat-free mass loss (FFML) are observed, which might relate to differences in protein intake and physical activity across patients. We performed repetitive assessments of protein intake and physical activity before and after banded Roux-en-Y gastric bypass surgery, and examined its relations to FFML during 6 months of follow-up. MATERIALS AND METHODS: FFML (bio-impedance analyses), protein intake (24-h dietary recalls) and moderate-to-vigorous physical activity (MVPA; activPAL) were assessed in 28 patients (4 males, age 42 ± 12 years) before surgery and at 1-, 3- and 6-months post-surgery. Changes in protein intake and MVPA were evaluated with mixed model analysis, whereas associations with FFML were assessed by univariate regression analysis. RESULTS: Six-month FFML was -7.3 ± 3.6 kg. Protein intake decreased from 80 ± 29 g/day (pre-surgery) to 45 ± 26 g/day (1 month post-surgery (P < 0.001)) and did not improve thereafter (51 ± 21 g/day; P > 0.05). Seven participants (25%) consumed ≥ 60 g protein/day at 6 months post-surgery. Participants performed 7394 ± 2420 steps/day in 54 ± 20 min/day of MVPA, which did not change from pre- to post-surgery (P > 0.05). A higher step count (B = -0.002; 95%CI = [-0.004 - 0.000]; P = 0.048) and higher level of MVPA (B = -0.29; 95%CI = [-0.54 - -0.03]; P = 0.018) were related to a lower FFML. CONCLUSION: A lower post-surgery FFML was attributable to higher MVPA levels but not protein intake. This may be due to the low total protein intake and the observation that only a minority of patients achieved a protein intake ≥ 60 g/day. Future studies should focus on interventions to increase post-bariatric protein intake and MVPA levels.

The association between wearable device metrics and clinical outcomes in oncology: A systematic review with evidence synthesis and meta-analysis.

BACKGROUND: The emerging study of wearable devices (WDs) in patients with cancer provides opportunities to harness real-time patient data for predicting clinical outcomes. We conducted a systematic review with best evidence synthesis to examine the association between WD metrics and clinical outcomes in patients with cancer. METHODS: MEDLINE and Embase were searched from inception until June 2022. Risk of bias assessment and best evidence synthesis were performed and, If possible, meta-analysis was conducted. RESULTS: A total of 34 studies was included. We found moderate-to-strong evidence for associations between circadian rest-activity metrics and OS. Disrupted I

Impact of tyrosine kinase inhibitors on glucose control and insulin regulation in patients with chronic myeloid leukemia.

Treatment with tyrosine kinase inhibitors (TKIs), especially nilotinib, often results in hyperglycemia, which may further increase cardiovascular disease risk in patients with chronic myeloid leukemia (CML). The mechanism underlying the TKI-induced glucose dysregulation is not clear. TKIs are suggested to affect insulin secretion but also insulin sensitivity of peripheral tissue has been proposed to play a role in the pathogenesis of TKI-induced hyperglycemia. Here, we aimed to assess whether skeletal muscle glucose uptake and insulin responses are altered in nondiabetic patients with CML receiving TKI treatment. After a glycogen-depleted exercise bout, an intravenous glucose bolus (0.3 g/kg body weight) was administered to monitor 2-h glucose tolerance and insulin response in 14 patients with CML receiving nilotinib, 14 patients with CML receiving imatinib, and 14 non-CML age- and gender-matched controls. A dynamic [18F]-FDG PET scan during a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 12 male patients with CML to assess m. quadriceps glucose uptake. We showed that patients with CML treated with nilotinib have an increased insulin response to intravenous glucose administration after muscle glycogen-depleted exercise. Despite the increased insulin response to glucose administration in patients with CML receiving nilotinib, glucose disappearance rates were significantly slower in nilotinib-treated patients when compared with controls in the first 15 min after glucose administration. Although [18F]-FDG uptake in m. quadriceps was not different, patients receiving nilotinib showed a trend toward decreased glucose infusion rates during euglycemic clamping when compared with patients receiving imatinib. Together, these findings indicate disturbed skeletal muscle glucose handling in patients with CML receiving nilotinib therapy.NEW & NOTEWORTHY In this study, we have shown that non-diabetic patients with CML receiving nilotinib therapy show early signs of disturbed skeletal muscle glucose handling, which was not observed in imatinib-treated patients. These observations in nilotinib users may reflect decreased muscle insulin sensitivity, which could serve as a potential target to counteract glycemic dysregulation, and is of clinical importance since these patients have an increased cardiovascular disease risk.

Impact of a COVID-19 infection on exercise levels of recreational athletes one- and three-months post-infection.

We examined the effect of a COVID-19 infection on changes in exercise levels in recreational athletes in the first three months after infection, and identified personal factors associated with a larger change in exercise level and recovery time. Recreational athletes (n=4360) completed an online questionnaire on health and exercise levels. 601 Athletes have had a diagnostically confirmed COVID-19 infection, while 3479 athletes did not (non-COVID-19 group). Exercise levels (in MET-min/week) were examined prior to (2019) and during the COVID-19 pandemic (2020) for the non-COVID-19 group, and in 2019, 1-month pre-COVID-19 infection, 1-month post-COVID-19 infection and 3 months post-COVID-19 infection in the COVID-19 group. Median exercise level at baseline in the COVID-19 group was 3528 (IQR=1488-5760) MET-min/week. One-month post-COVID-19 infection, exercise level dropped 58% (2038 MET-min/week), which partly stabilized to 36% (1256 MET-min/week) below baseline values 3 months post-COVID-19 infection. Moreover, in both the COVID-19 (pre-COVID-19 infection) and non-COVID-19 group exercise levels during the pandemic decreased with ~260 MET-min/week. These results illustrate that even a relatively physically active population of recreational athletes is significantly affected by a COVID-19 infection, particularly those athletes who are overweight. COVID-19 disease burden, age, sex, comorbidities and smoking were not associated with reduced exercise levels.

The magnitude and progress of lean body mass, fat-free mass, and skeletal muscle mass loss following bariatric surgery: A systematic review and meta-analysis.

Postbariatric loss of muscle tissue could negatively affect long-term health due to its role in various bodily processes, such as metabolism and functional capacity. This meta-analysis aimed to unravel time-dependent changes in the magnitude and progress of lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss following bariatric surgery. A systematic literature search was conducted in Pubmed, Embase, and Web of Science. Fifty-nine studies assessed LBM (n = 37), FFM (n = 20), or SMM (n = 3) preoperatively and ≥1 time points postsurgery. Random-effects meta-analyses were performed to determine pooled loss per outcome parameter and follow-up time point. At 12-month postsurgery, pooled LBM loss was -8.13 kg [95%CI -9.01; -7.26]. FFM loss and SMM loss were -8.23 kg [95%CI -10.74; -5.73] and -3.18 kg [95%CI -5.64; -0.71], respectively. About 55% of 12-month LBM loss occurred within 3-month postsurgery, followed by a more gradual decrease up to 12 months. Similar patterns were seen for FFM and SMM. In conclusion, >8 kg of LBM and FFM loss was observed within 1-year postsurgery. LBM, FFM, and SMM were predominantly lost within 3-month postsurgery, highlighting that interventions to mitigate such losses should be implemented perioperatively.

Dose-response association between moderate to vigorous physical activity and incident morbidity and mortality for individuals with a different cardiovascular health status: A cohort study among 142,493 adults from the Netherlands.

BACKGROUND: Moderate to vigorous physical activity (MVPA) is strongly associated with risk reductions of noncommunicable diseases and mortality. Cardiovascular health status may influence the benefits of MVPA. We compare the association between MVPA and incident major adverse cardiovascular events (MACE) and mortality between healthy individuals, individuals with elevated levels of cardiovascular risk factors (CVRF), and cardiovascular disease (CVD). METHODS AND FINDINGS: A cohort study was performed in the 3 northern provinces of the Netherlands, in which data were collected between 2006 and 2018, with a median follow-up of 6.8 years (Q25 5.7; Q75 7.9). A total of 142,493 participants of the Lifelines Cohort Study were stratified at baseline as (1) healthy; (2) CVRF; or (3) CVD. Individuals were categorized into "inactive" and 4 quartiles of least (Q1) to most (Q4) active based on self-reported MVPA volumes. Primary outcome was a composite of incident MACE and all-cause mortality during follow-up. Cox regression was used to estimate hazard ratios (HRs), 95% confidence intervals (CIs) and P values. The main analyses were stratified on baseline health status and adjusted for age, sex, income, education, alcohol consumption, smoking, protein, fat and carbohydrate intake, kidney function, arrhythmias, hypothyroid, lung disease, osteoarthritis, and rheumatoid arthritis. The event rates were 2.2% in healthy individuals (n = 2,485 of n = 112,018), 7.9% in those with CVRF (n = 2,214 of n = 27,982) and 40.9% in those with CVD (n = 1,019 of n = 2,493). No linear association between MVPA and all-cause mortality or MACE was found for healthy individuals (P = 0.36) and individuals with CVRF (P = 0.86), but a linear association was demonstrated for individuals with CVD (P = 0.04). Adjusted HRs in healthy individuals were 0.81 (95% CI 0.64 to 1.02, P = 0.07), 0.71 (95% CI 0.56 to 0.89, P = 0.004), 0.72 (95% CI 0.57 to 0.91, P = 0.006), and 0.76 (95% CI 0.60 to 0.96, P = 0.02) for MVPA Q1 to Q4, respectively, compared to inactive individuals. In individuals with CVRF, HRs were 0.69 (95% CI 0.57 to 0.82, P < 0.001), 0.66 (95% CI 0.55 to 0.80, P < 0.001), 0.64 (95% CI 0.53 to 0.77, P < 0.001), and 0.69 (95% CI 0.57 to 0.84, P < 0.001) for MVPA Q1 to Q4, respectively, compared to inactive individuals. Finally, HRs for MVPA Q1 to Q4 compared to inactive individuals were 0.80 (95% CI 0.62 to 1.03, P = 0.09), 0.82 (95% CI 0.63 to 1.06, P = 0.13), 0.74 (95% CI 0.57 to 0.95, P = 0.02), and 0.70 (95% CI 0.53 to 0.93, P = 0.01) in CVD patients. Leisure MVPA was associated with the most health benefits, nonleisure MVPA with little health benefits, and occupational MVPA with no health benefits. Study limitations include its observational nature, self-report data about MVPA, and potentially residual confounding despite extensive adjustment for lifestyle risk factors and health-related factors. CONCLUSIONS: MVPA is beneficial for reducing adverse outcomes, but the shape of the association depends on cardiovascular health status. A curvilinear association was found in healthy and CVRF individuals with a steep risk reduction at low to moderate MVPA volumes and benefits plateauing at high(er) MVPA volumes. CVD patients demonstrated a linear association, suggesting a constant reduction of risk with higher volumes of MVPA. Therefore, individuals with CVDs should be encouraged that "more is better" regarding MVPA. These findings may help to optimize exercise prescription to gain maximal benefits of a physically active lifestyle.

Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users.

BACKGROUND: The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations. OBJECTIVES: This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users. METHODS: Symptomatic (n = 16; age 64 ± 4 years) and asymptomatic statin users (n = 16; age 64 ± 4 years) and nonstatin using control subjects (n = 20; age 63 ± 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization. RESULTS: Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01). CONCLUSIONS: A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346).

Impact of prolonged sitting and physical activity breaks on cognitive performance, perceivable benefits, and cardiometabolic health in overweight/obese adults: The role of meal composition.

BACKGROUND & AIMS: Physical activity (PA) breaks may effectively attenuate the detrimental impact of prolonged sitting on acute cognitive performance, perceivable benefits (e.g. mood), vascular function, and metabolic health. To date, the impact of meal composition on the effects of sedentary behavior and/or PA breaks on health has been scarcely studied. Therefore, our aim was to investigate whether meal composition alters how sedentary behavior and PA breaks affect these acute health outcomes. METHODS: A total of 24 overweight and obese, sedentary adults completed four conditions in randomized order in a cross-over design: [a] high-protein, low-fat breakfast (HPLF) + 4hrs uninterrupted sitting (SIT), [b] HPLF + 4hrs interrupted sitting (ACT; 5-min cycling every 30 min), [c] Western breakfast (WEST; higher in fats/simple sugars, lower in protein/fiber) + SIT, [d] WEST + ACT. WEST and HPLF were isocaloric. Linear mixed models were used to examine changes in cognitive performance (Test of Attentional Performance), perceivable benefits (Likert-scales, Profile of Mood States questionnaire), vascular health (carotid artery reactivity, blood pressure), and metabolic health (post-breakfast glucose, insulin, lipids). RESULTS: Independent of meal composition, we did not observe any effect of PA breaks on cognitive performance, vascular health and post-breakfast lipid responses. PA breaks delayed post-breakfast mood and vigor decrements, as well as increases in fatigue and sleepiness (all p < 0.05), but effects were independent of meal composition (p > 0.05). WEST resulted in higher post-breakfast glucose levels compared to HPLF (p < 0.05), while PA breaks did not impact this response (p > 0.05). PA breaks reduced post-breakfast insulin (p < 0.05), which did not differ between meals (p > 0.05). CONCLUSIONS: The acute impact of PA breaks and/or prolonged sitting on cognitive performance, perceivable benefits, and vascular and metabolic health was not altered by the composition of a single meal in overweight/obese, sedentary adults. Possibly, breaking up prolonged sitting, rather than meal composition, is a more potent strategy to impact acute health outcomes, such as perceivable benefits and insulin levels.

Changes in Physical Activity in Relation to Body Composition, Fitness and Quality of Life after Primary Bariatric Surgery: a Two-Year Follow-Up Study.

PURPOSE: The success of bariatric surgery varies largely, which may relate to variance in adopting a physically active lifestyle. This study aimed to determine whether two-year changes in physical activity (PA) were associated with weight loss, fat-free mass, cardiorespiratory fitness and quality of life up to two years after bariatric surgery. MATERIALS AND METHODS: In this retrospective study, 3879 post-bariatric patients were divided into three groups: 1) decreased PA (n = 388), 2) maintained PA (n = 2002) or 3) increased PA (n = 1498). Measurements regarding PA (Baecke questionnaire), body composition (bioelectrical impedance analysis), estimated cardiorespiratory fitness (Åstrand test) and health-related quality of life (RAND-36) were performed preoperatively and two years post-surgery. RESULTS: Bariatric patients with increased PA had greater excess weight loss (76.3% vs. 73.2% vs. 72.9%, P < 0.001), greater increases in %fat-free mass (Δ14.0% vs. 13.0% vs. 12.8%; P < 0.001), larger improvements in VO2max (Δ11.8 vs. 10.2 vs. 8.0 ml/kg/min, P < 0.001), and larger increases in health related quality of life subscale scores (P < 0.05) compared to patients with maintained- and decreased PA. CONCLUSIONS: Bariatric patients who managed to induce improvements in habitual physical activity had better body composition, fitness and quality of life at 2 years post-surgery, compared to patients who maintained or even reduced their PA levels. These findings underscore the importance of perioperative-bariatric care programs to change lifestyle and achieve sustainable improvements in PA levels.

No signs of subclinical atherosclerosis after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10-40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system. METHODS: This cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models. RESULTS: Mean CIMT was 692.7 µm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (ß=0.68 µm; 95% CI -4.02, 5.38) and PWV (ß=44 mm/s; 95% CI -32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers. CONCLUSIONS: We found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.

Repeated prolonged moderate-intensity walking exercise does not appear to have harmful effects on inflammatory markers in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: The role of exercise in the management of inflammatory bowel disease (IBD) is inconclusive as most research focused on short or low-intensity exercise bouts and subjective outcomes. We assessed the effects of repeated prolonged moderate-intensity exercise on objective inflammatory markers in IBD patients. METHODS: In this study, IBD patients (IBD walkers, n = 18), and a control group (non-IBD walkers, n = 19), completed a 30, 40 or 50 km walking exercise on four consecutive days. Blood samples were taken at baseline and every day post-exercise to test for the effect of disease on exercise-induced changes in cytokine concentrations. A second control group of IBD patients who did not take part in the exercise, IBD non-walkers (n = 19), was used to test for the effect of exercise on faecal calprotectin. Both IBD groups also completed a clinical disease activity questionnaire. RESULTS: Changes in cytokine concentrations were similar for IBD walkers and non-IBD walkers (IL-6 p = .95; IL-8 p = .07; IL-10 p = .40; IL-1ß p = .28; TNF-α p = .45), with a temporary significant increase in IL-6 (p < .001) and IL-10 (p = .006) from baseline to post-exercise day 1. Faecal calprotectin was not affected by exercise (p = .48). Clinical disease activity did not change in the IBD walkers with ulcerative colitis (p = .92), but did increase in the IBD walkers with Crohn's disease (p = .024). CONCLUSION: Repeated prolonged moderate-intensity walking exercise led to similar cytokine responses in participants with or without IBD, and it did not affect faecal calprotectin concentrations, suggesting that IBD patients can safely perform this type of exercise.

Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity.

Fatigue is a common side effect of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients. However, the prevalence of TKI-induced fatigue remains uncertain and little is known about predictors of fatigue and its relationship with physical activity. In this study, 220 CML patients receiving TKI therapy and 110 gender- and age-matched controls completed an online questionnaire to assess fatigue severity and fatigue predictors (Part 1). In addition, physical activity levels were objectively assessed for 7 consecutive days in 138 severely fatigued and non-fatigued CML patients using an activity monitor (Part 2). We demonstrated that the prevalence of severe fatigue was 55.5% in CML patients and 10.9% in controls (P<0.001). We identified five predictors of fatigue in our CML population: age (OR 0.96, 95% CI 0.93-0.99), female gender (OR 1.76, 95% CI 0.92-3.34), Charlson Comorbidity Index (OR 1.91, 95% CI 1.16-3.13), the use of comedication known to cause fatigue (OR 3.43, 95% CI 1.58-7.44), and physical inactivity (OR of moderately active, vigorously active and very vigorously active compared to inactivity 0.43 (95% CI 0.12-1.52), 0.22 (95% CI 0.06-0.74), and 0.08 (95% CI 0.02-0.26), respectively). Objective monitoring of activity patterns confirmed that fatigued CML patients performed less physical activity on both light (P=0.017) and moderate to vigorous intensity (P=0.009). In fact, compared to the non-fatigued patients, fatigued CML patients performed 1 hour less of physical activity per day and took 2000 fewer steps per day. Our findings facilitate the identification of patients at risk of severe fatigue and highlight the importance to set the reduction of fatigue as a treatment goal in CML care. This study was registered at The Netherlands Trial Registry, NTR7308 (Part 1) and NTR7309 (Part 2).

Association of Cardiac Rehabilitation With All-Cause Mortality Among Patients With Cardiovascular Disease in the Netherlands.

Importance: Cardiac rehabilitation (CR) is an effective strategy to improve clinical outcomes, but it remains underused in some subgroups of patients with cardiovascular disease (CVD). Objective: To investigate the implications of sex, age, socioeconomic status, CVD diagnosis, cardiothoracic surgery, and comorbidity for the association between CR participation and all-cause mortality. Design, Setting, and Participants: Observational cohort study with patient enrollment between July 1, 2012, and December 31, 2017, and a follow-up to March 19, 2020. The dates of analysis were March to May 2020. This study was performed among Dutch patients with CVD with a multidisciplinary outpatient CR program indication and who were insured at Coöperatie Volksgezondheidszorg, one of the largest health insurance companies in the Netherlands. Among 4.1 million beneficiaries, patients with CVD with an acute coronary event (myocardial infarction or unstable angina pectoris), stable angina pectoris, chronic heart failure, or cardiothoracic surgery (coronary artery bypass grafting, valve replacement, or percutaneous coronary intervention) were identified by inpatient diagnosis codes and included in the study. Main Outcomes and Measures: Cox proportional hazards models were used to evaluate the association between CR participation and all-cause mortality. Stabilized inverse propensity score weighting was used to account for patient and disease characteristics associated with CR participation. Results: Among 83 687 eligible patients with CVD (mean [SD] age, 67 [12] years; 60.4% [n = 50 512] men), only 31.3% (n = 26 171) participated in CR, with large variation across different subgroups (range, 5.1%-73.0%). During a mean (SD) of 4.7 (1.8) years of follow-up, 1966 CR participants (7.5%) and 13 443 CR nonparticipants (23.4%) died. After multivariable adjustment, CR participation was associated with a 32% lower risk of all-cause mortality (adjusted hazard ratio, 0.68; 95% CI, 0.65-0.71) compared with nonparticipation. Sex, age, socioeconomic status, and comorbidity did not alter risk reduction after CR participation, but a statistically significant interaction association was found across categories of CVD diagnosis and cardiothoracic surgery. Larger reductions in risk estimates for all-cause mortality were found after CR participation for STEMI (adjusted HR, 0.59; 95% CI, 0.52-0.68 vs 0.72; 95% CI, 0.65-0.79; P < .001), NSTEMI (adjusted HR, 0.64; 95% CI, 0.58-0.70 vs 0.72; 95% CI, 0.65-0.79; P < .001), and stable AP (adjusted HR, 0.69; 95% CI, 0.63-0.76 vs 0.72; 95% CI, 0.65-0.79; P < .001) compared with patients with chronic heart failure, whereas unstable AP had a smaller risk reduction (adjusted HR, 0.75; 95% CI, 0.67-0.85 vs 0.72; 95% CI, 0.65-0.79; P < .001). Conclusions and Relevance: In this cohort study, CR participation was associated with a 32% risk reduction in all-cause mortality, and this benefit was independent of sex, age, socioeconomic status, and comorbidity. These findings reinforce the importance of CR participation in secondary prevention and highlight the possibility that CR should be prescribed more widely to vulnerable patients with CVD, such as older adults with chronic diseases or multimorbidity.

Rate and Determinants of Excessive Fat-Free Mass Loss After Bariatric Surgery.

PURPOSE: Fat-free mass (FFM) loss is a concerning aspect of bariatric surgery, but little is known about its time-course and factors related with excessive FFM loss. This study examined (i) the progress of FFM loss up to 3 years post-bariatric surgery and (ii) the prevalence and determinants of excessive FFM loss. MATERIALS AND METHODS: A total of 3596 patients (20% males, 43.5 ± 11.1 years old, BMI = 44.2 ± 5.5 kg/m2) underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. Bioelectrical impedance analysis was performed preoperatively and 3, 6, 9, 12, 18, 24 and 36 months post-surgery. Changes in body composition were assessed by mixed model analysis. Prevalence of excessive FFM loss (based on three different cutoff values: ≥ 25%, ≥ 30% and ≥ 35% FFM loss/weight loss (= %FFML/WL)) was estimated and its determinants were assessed by linear regression analysis. RESULTS: Highest rates of FFM loss were found at 3 and 6 months post-surgery, reflecting 57% and 73% of peak FFM loss, respectively. Prevalence of excessive FFM loss ranged from 14 to 46% at 36 months post-surgery, with an older age (ß = 0.14, 95%CI = 0.10-0.18, P < .001), being male (ß = 3.99, 95%CI = 2.86-5.12, P < .001), higher BMI (ß = 0.13, 95%CI = 0.05-0.20, P = .002) and SG (ß = 2.56, 95%CI = 1.36-3.76, P < .001) as determinants for a greater %FFML/WL. CONCLUSION: Patients lost most FFM within 3 to 6 months post-surgery. Prevalence of excessive FFM loss was high, emphasizing the need for more vigorous approaches to counteract FFM loss. Furthermore, future studies should assess habitual physical activity and dietary intake shortly after surgery in relation to FFM loss.

Correlates of Total and domain-specific Sedentary behavior: a cross-sectional study in Dutch adults.

BACKGROUND: Sedentary behavior (SB) is associated with increased risks of detrimental health outcomes. Few studies have explored correlates of SB in physically active individuals. Furthermore, SB correlates may depend on settings of SB, such as occupation, transportation and leisure time sitting. This study aims to identify subject-, lifestyle- and health-related correlates for total SB and different SB domains: transportation, occupation, and leisure time. METHODS: Dutch participants were recruited between June, 2015 and December, 2016. Participant characteristics (i.e. age, sex, weight, height, marital status, education level, employment), lifestyle (sleep, smoking, alcohol consumption, physical activity) and medical history were collected via an online questionnaire. SB was assessed using the Sedentary Behavior Questionnaire and estimated for 9 different activities during weekdays and weekend days. Logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between correlates and SB. Total SB was dichotomized at > 8 h/day and > 10 h/day, and being sedentary during transportation, occupation and leisure time at the 75th percentile (60 min/day, 275 min/day and 410 min/day, respectively). RESULTS: In total, 8471 participants (median age 55, 55% men) were included of whom 86% met the physical activity guidelines. Median SB was 9.1 h/day (Q25 6.3-Q75 12.0) during weekdays and 7.4 h/day (Q25 5.5-Q75 9.5) during weekend days. SB was most prevalent during leisure time (5.3 h/day; Q25 3.9-Q75 6.8), followed by occupation (2 h/day; Q25 0.1-Q75 4.6) and transportation (0.5 h/day; Q25 0.2-Q75 1.0). Younger age, male sex, being unmarried, higher education, employment and higher BMI were significantly related to higher levels of total SB. Younger age, male sex, employment, and higher BMI increased the odds for high SB volumes during occupation and transportation. Higher education, being unmarried and smoking status were positively associated with high volumes of occupational SB only, whereas older age, being unmarried, unemployment, higher BMI and poor health were positively linked to leisure time SB. CONCLUSIONS: SB is highly prevalent in physically active individuals, with SB during leisure time as the most important contributor. Correlates for high volumes of SB vary substantially across SB domains, emphasizing the difficulty to target this unhealthy lifestyle.