Contrast-enhanced ultrasonography (CEUS) reveals active bleeding into an abdominal hematoma in a patient with ongoing subcutaneous injections.

A 95-year-old woman with metastasizing bronchial carcinoma presents with left inguinal pain. The referring physician would like to exclude an inguinal hernia and a deep vein thrombosis due to her precondition of essential thrombocythemia. Conventional ultrasound excluded the presence of a deep vein thrombosis yet showed a 6 cm × 5 cm hematoma distal of the left m. rectus abdominis. The subsequently performed color Doppler examination excluded a pseudoaneurysm but could not preclude active bleeding. Eventually, CEUS showed contrast-pooling within the hematoma as a sign of active extravasation, suggesting ongoing bleeding.

Impact of sedentary behavior on large artery structure and function in children and adolescents: a systematic review.

Sedentary behavior contributes to increased atherosclerotic risk in adults. Whether or not this can be extended to pediatric populations is unclear. This systematic review assessed associations of sedentary behavior with large artery structure and function in pediatric populations. MEDLINE, EMBASE, CENTRAL, and Web of Science were searched from the earliest available date to 31st of December 2018. Analyses of associations of sedentary behavior with large artery structure or function in a pediatric (sub-)population were included, adhering to the PRISMA guidelines. The protocol was published in advance on PROSPERO (CRD42018112996). Study quality and quality of evidence were analyzed using NHLBI Study Quality assessment tools and GRADE. Six observational studies found no association of exposure and outcome variables, and one had contradicting results. One intervention found reduced flow-mediated dilation after 3 h of uninterrupted sitting. Exposure and outcome measures were highly heterogeneous. Study quality was low to moderate. Quality of evidence was very low or low in the observational studies and high in the intervention.Conclusion: In pediatric populations, current evidence is limited and of low quality about how acute effects of sedentary behavior translate into early vascular aging and the long-term development of vascular dysfunction and atherosclerotic risk. Future studies should emphasize a careful choice of the adequate type and measurement site of a biomarker for large artery structure and function as well as conduct a detailed assessment of sedentary behavior patterns.Trial registration: PROSPERO Registration Number: CRD42018112996What is known: • An independent association of sedentary behavior and biomarkers of large artery structure and function has been demonstrated in adults. • In children, sedentary behavior is directly associated with classical cardiovascular risk factors like elevated blood glucose levels, insulin resistance, high blood pressure, obesity, and elevated blood lipids.What is new: • Currently, only few studies of low quality in children and adolescents provide limited evidence about how acute effects of sedentary behavior translate into early vascular aging and the long-term development of atherosclerosis. • The type and measurement site of vascular biomarker need to be chosen carefully, and a detailed assessment of sedentary behavior patterns is important to minimize the methodological bias.

Dynamic MR imaging of the skeletal muscle in young and senior volunteers during synchronized minimal neuromuscular electrical stimulation.

OBJECTIVE: Neuromuscular electrical stimulation (NMES)-induced isometric contraction is feasible during MRI and can be combined with acquisition of volumetric dynamic MR data, in a synchronous and controlled way. Since NMES is a potent resource for rehabilitation, MRI synchronized with NMES presents a valuable validation tool. Our aim was to show how minimal NMES-induced muscle contraction characterization, as evaluated through phase-contrast MRI, differs between senior and young volunteers. MATERIALS AND METHODS: Simultaneous NMES of the quadriceps muscle and phase-contrast imaging were applied at 3 T to 11 senior (75 ± 3 years) and 12 young volunteers (29 ± 7 years). A current sufficient to induce muscle twitch without knee extension was applied to both groups. RESULTS: Strain vectors were extracted from the velocity fields and strain datasets were compared with non-parametric tests and descriptive statistics. Strain values were noticeably different between both groups at both current intensities and significant differences were observed for similar current level. DISCUSSION: In conclusion, NMES-synchronized MRI could be successfully applied in senior volunteers with strain results clearly different from the younger volunteers. Also, differences within the senior group were detected both in the magnitude of strain and in the position of maximum strain pixels.

Physical activity is favorably associated with arterial stiffness in patients with obesity and elevated metabolic risk.

OBJECTIVES: Physical activity and cardiorespiratory fitness (CRF) are relevant modifiers of cardiovascular risk. Their independent effects on arterial stiffness have not been assessed in people with obesity. This study aimed to assess the independent effects of light (LPA) and moderate-to-vigorous (MVPA) physical activity and CRF on Pulse wave velocity (PWV). METHODS: Brachial-ankle PWV (baPWV) was measured cross-sectionally in 55 subjects (43.0 ± 13.8 years; 66% women) with moderate cardiovascular risk. Body composition was assessed with bioelectrical impedance-analysis. Daily minutes of LPA and MVPA were measured by accelerometry and CRF (peak oxygen uptake [VO2 peak]) with spiroergometry. Independent effects of LPA, MVPA, and VO2 peak on baPWV were analyzed in an age-, sex-, body fat mass-, and blood pressure-adjusted ANOVA. RESULTS: Every 10 minutes increase of daily MVPA was associated with a 2.8% (0.32m/s [-0.64 to 0.001 m/s], P = .05) reduction of baPWV, whereas LPA and VO2 peak had only a little or no relevant effects on baPWV. CONCLUSIONS: Higher MVPA is associated with lower composite arterial stiffness independent of CRF and the number of metabolic risk factors in patients with obesity and further metabolic risk factors. Thus, lifestyle interventions should aim for an increase in MVPA. BaPWV may improve the monitoring of favorable effects of MVPA, even if an improvement of VO2 peak cannot be obtained.

Association of cardiorespiratory fitness with retinal vessel diameters as a biomarker of cardiovascular risk.

OBJECTIVE: We aimed to investigate the association of retinal microvascular health with cardiorespiratory fitness (VO2peak) and cardiovascular risk factors. METHODS: In a population of 260 obesity-enriched participants we investigated the association of retinal vessel diameters with cardiorespiratory fitness (CRF), body mass index (BMI) and blood pressure (BP). Retinal vessel imaging was performed by use of a fundus camera and a semi-automated processing software, calculating the central retinal arteriolar (CRAE) and venular equivalent (CRVE) as well as the arteriolar-to-venular diameter ratio (AVR). RESULTS: Participants had a mean age of 45.8 ±â€¯12.5 years and a BMI of 35.8 ±â€¯6.8 kg/m2. 45% of patients were diagnosed with hypertension, 26% with diabetes and 30% with dyslipidemia. Increasing VO2peak was independently associated with lower CRVE (ß = -0.600; CI -1.141, -0.060; p = 0.030). Higher BMI and mean arterial pressure were independently associated with narrower CRAE (ß = -0.492; CI -0.909, -0.076; p = 0.021 and ß = -0.268; CI -0.471, -0.066; p = 0.009, respectively) and lower AVR (ß = -0.002; CI -0.003, -0.000; p = 0.026 and ß = -0.001; CI -0.002, -0.000; p = 0.001, respectively). CONCLUSIONS: Higher cardiorespiratory fitness is associated with beneficial retinal microvascular health. Higher BMI and BP were associated with an impairment of retinal microvascular health. Exercise is known for its potential to improve body composition and reduce BP but may also prove to be an efficient therapy to counteract small vessel disease in cardiometabolic disease.

Effects of bright and blue light on acoustic reaction time and maximum handgrip strength in male athletes: a randomized controlled trial.

PURPOSE: To assess which type of evening light exposure has the greatest effect on reaction time and maximum handgrip strength. These were pre-specified secondary outcomes in a trial which primarily investigated the influence of light on cycling performance. METHODS: Seventy-four male athletes were allocated at random to either bright light (BRIGHT), monochromatic blue light (BLUE), or a control condition (CONTROL). Light exposure lasted for 60 min and started 17 h after the individual midpoint of sleep. Reaction time, handgrip strength, and melatonin levels were measured before and after the light exposure. We used analysis of covariance to compare the groups with respect to the investigated outcomes. RESULTS: Two participants had to be excluded retrospectively. The remaining 72 participants had a median age of 23 years. The adjusted difference in reaction time was -1 ms [95% confidence interval (CI) -8, 6] for participants in BRIGHT and 2 ms (95% CI -5, 9) for participants in BLUE, both relative to participants in CONTROL. The adjusted difference in handgrip strength was 0.9 kg (95% CI -1.5, 3.3) for participants in BRIGHT and -0.3 kg (95% CI -2.7, 2.0) for participants in BLUE, both relative to participants in CONTROL. After the light exposure, 17% of participants in BRIGHT, 22% in BLUE, and 29% in CONTROL showed melatonin concentrations of 2 pg/ml or higher. CONCLUSIONS: The results suggest that bright light might reduce melatonin levels but neither bright nor blue light exposure in the evening seem to improve reaction time or handgrip strength in athletes.

Speeding up PET/MR for cancer staging of children and young adults.

OBJECTIVE: Combining 18F-FDG PET with whole-body MR for paediatric cancer staging is practically feasible if imaging protocols can be streamlined. We compared 18F-FDG PET/STIR with accelerated 18F-FDG PET/FSPGR for whole-body tumour imaging in children and young adults. METHODS: Thirty-three children and young adults (17.5 ± 5.5 years, range 10-30) with malignant lymphoma or sarcoma underwent a 18F-FDG PET staging examination, followed by ferumoxytol-enhanced STIR and FSPGR whole-body MR. 18F-FDG PET scans were fused with MR data and the number and location of tumours on each integrated examination were determined. Histopathology and follow-up imaging served as standard of reference. The agreement of each MR sequence with the reference and whole-body imaging times were compared using Cohen's kappa coefficient and Student's t-test, respectively. RESULTS: Comparing 18F-FDG PET/FSPGR to 18F-FDG PET/STIR, sensitivities were 99.3 % for both, specificities were statistically equivalent, 99.8 versus 99.9 %, and the agreement with the reference based on Cohen's kappa coefficient was also statistically equivalent, 0.989 versus 0.992. However, the total scan-time for accelerated FSPGR of 19.8 ± 5.3 minutes was significantly shorter compared to 29.0 ± 7.6 minutes for STIR (p = 0.001). CONCLUSION: F-FDG PET/FSPGR demonstrated equivalent sensitivities and specificities for cancer staging compared to 18F-FDG PET/STIR, but could be acquired with shorter acquisition time. KEY POINTS: • Breath-hold FSPGR sequences shorten the data acquisition time for whole-body MR and PET/MR. • Ferumoxytol provides long-lasting vascular contrast for whole-body MR and PET/MR. • 18 F-FDG PET/FSPGR data provided equal sensitivity and specificity for cancer staging compared to 18 F-FDG PET/STIR.

Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study.

BACKGROUND: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. METHODS: We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. FINDINGS: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. INTERPRETATION: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. FUNDING: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

Cardiorespiratory Fitness and Endothelial Function in Aging Healthy Subjects and Patients With Cardiovascular Disease.

Background: Individuals with a higher lifelong cardiorespiratory fitness show better vascular health with aging. Studies on fitness-related effects on endothelial function either analyzed samples with a narrow age-range or incompletely assessed endothelial responsiveness. This study aims to assess the impact of cardiorespiratory fitness on the association of brachial-arterial flow-mediated vasodilation (FMD) and low flow-mediated vasoconstriction (L-FMC) with age in healthy adults and patients with cardiovascular diseases. Methods: FMD, L-FMC and V . O2peak were prospectively measured in a population-based sample including 360 healthy adults and 99 patients with cardiovascular disease of European descend. Non-linear models were applied to assess V . O2peak-associated variations in age-related differences of endothelial function independent of classical cardiovascular risk factors. Results: FMD was negatively associated with age in healthy adults (adjusted R2 = 0.27, partial R2 = 0.07, p < 0.001) and in cardiovascular patients (adjusted R2 = 0.29, partial R2 = 0.05, p = 002). L-FMC showed no association with age. In models predicting the change of FMD with higher age, V . O2peak accounted for 2.8% of variation in FMD (χ2(5) = 5.37, p = 0.372, s = 1.43). Thereby, V . O2peak-stratified changes of FMD started to fan out at around 30 years of age in women and 50 years of age in men, with 7-12% lower values at old age with V . O2peak ≤3rd percentile compared to V . O2peak ≥97th percentile) in both, the healthy sample and in cardiovascular patients. Conclusion: The statistical effect of cardiorespiratory fitness on the association of FMD with age independent of classical cardiovascular risk factors was small in both, healthy aging adults as well as patients with cardiovascular diseases. Its clinical significance should be assessed further.

Ideal Life's Simple 7 Score Relates to Macrovascular Structure and Function in the Healthy Population.

BACKGROUND: Cardiovascular health scores, such as Life's Simple 7 from the American Heart Association, and the assessment of arterial properties are independently used to determine cardiovascular risk. However, evidence of their association remains scarce, especially in healthy, middle-aged to older populations. METHODS: A healthy sample of the Swiss population aged 50-91 years as part of the COmPLETE cohort study was included. Carotid intima-media thickness (cIMT), carotid lumen diameter (cLD), carotid distensibility coefficient (DC), flow-mediated dilation (FMD), and brachial-ankle pulse wave velocity (baPWV) were used to determine arterial properties. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body-mass index, cholesterol, systolic blood pressure, hemoglobin A1c, smoking status, physical activity, and diet). In accordance with the American Heart Association, for each category, two points were given for an ideal health metric level, intermediate scores one point, and poor scores zero points. Intermediate and ideal health scores corresponded to a total of 5-9 and 10-14 points, respectively. RESULTS: A total of 280 participants (50.7% male) were included. After adjusting for age and sex, an ideal health score was associated with lower cIMT (-0.038 mm, 95% CI: -0.069 mm--0.007 mm, p = 0.017), lower cLD (-0.28 mm, 95% CI: -0.46 mm--0.11 mm, p = 0.002), and lower baPWV (-0.05 m/s, 95% CI: -0.08 m/s--0.02 m/s, p = 0.003). No differences were found for FMD and DC. CONCLUSIONS: Even in a healthy sample of middle-aged and older adults, individuals with an ideal cardiovascular health score showed more favorable biomarkers of vascular aging than those with an intermediate score. This stresses the relevance of promoting an optimal lifestyle, even among the healthy population.

Verification-phase tests show low reliability and add little value in determining [Formula: see text]O2max in young trained adults.

OBJECTIVE: This study compared the robustness of a [Formula: see text]-plateau definition and a verification-phase protocol to day-to-day and diurnal variations in determining the true [Formula: see text]. Further, the additional value of a verification-phase was investigated. METHODS: Eighteen adults performed six cardiorespiratory fitness tests at six different times of the day (diurnal variation) as well as a seventh test at the same time the sixth test took place (day-to-day variation). A verification-phase was performed immediately after each test, with a stepwise increase in intensity to 50%, 70%, and 105% of the peak power output. RESULTS: Participants mean [Formula: see text] was 56 ± 8 mL/kg/min. Gwet's AC1 values (95% confidence intervals) for the day-to-day and diurnal variations were 0.64 (0.22, 1.00) and 0.71 (0.42, 0.99) for [Formula: see text]-plateau and for the verification-phase 0.69 (0.31, 1.00) and 0.07 (-0.38, 0.52), respectively. In 66% of the tests, performing the verification-phase added no value, while, in 32% and 2%, it added uncertain value and certain value, respectively, in the determination of [Formula: see text]. CONCLUSION: Compared to [Formula: see text]-plateau the verification-phase shows lower reliability, increases costs and only adds certain value in 2% of cases.

Endothelial function of healthy adults from 20 to 91 years of age: prediction of cardiovascular risk by vasoactive range.

OBJECTIVES: Brachial arterial low flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) are ultrasound-based biomarkers that emerge into scientific and clinical practice indicating cardiovascular effects of medical and lifestyle-based treatment beyond classical risk factors. This study is the first to provide reference values and to assess the predictive value of L-FMC, FMD and their composite endpoint vasoactive range (VAR) in healthy adults. METHODS: L-FMC, FMD and VAR were measured in 457 nonsmoking adults of 20-91 years without chronic diseases, medication, with normal heart function and very low cardiovascular risk. Sex-specific percentiles were calculated and predictive ability for elevated cardiovascular risk was assessed using receiver-operating characteristic (ROC) curves. RESULTS: From 20 to 91 years of age, L-FMC increased 86.1 and 105.3%, FMD decreased 63.6 and 47.1% and VAR decreased 58.3 and 55.2% in women and men, respectively. Area under the ROC curves was 0.54 (95% CI = 0.49-0.54) for L-FMC, 0.67 (95% CI = 0.62-0.67) for FMD and 0.72 (95% CI = 0.67-0.72) for VAR (P < 0.001). Discriminatory cut-offs for elevated risk were 0.24% for L-FMC (sensitivity = 0.42, specificity = 0.67), 6.4% for FMD (sensitivity = 0.71, specificity = 0.60) and 6.3% for VAR (sensitivity = 0.62, specificity = 0.73). CONCLUSION: This study demonstrates reduced endothelial function with aging in healthy men and women with very low cardiovascular risk. Percentiles crossed cut-offs for elevated cardiovascular risk between 50 and 55 years in men and 70 and 75 years in women, indicating higher risk for cardiovascular disease in men. VAR showed the highest ability to identify individuals with elevated cardiovascular risk, and should be included in the monitoring and treatment of accelerated vascular aging even in healthy individuals.

Novel CPET Reference Values in Healthy Adults: Associations with Physical Activity.

PURPOSE: Cardiopulmonary exercise testing (CPET) is an important measurement in clinical practice, and its primary outcome, maximal oxygen uptake (V˙O2peak), is inversely associated with morbidity and mortality. The purposes of this study are to provide CPET reference values for maximal and submaximal parameters across the adult age spectrum of a healthy European cohort, to compare V˙O2peak values with other reference data sets, and to analyze the associations between physical activity (PA) levels and CPET parameters. METHODS: In this cross-sectional study, we prospectively recruited 502 participants (47% female) from 20 to 90 yr old. The subjects performed a CPET on a cycle ergometer using a ramp protocol. PA was objectively and continuously measured over 14 d using a triaxial accelerometer. Quantile curves were calculated for CPET parameters. To investigate the associations between CPET parameters and PA levels, linear regression analysis was performed. RESULTS: V˙O2peak values observed in the group of 20-29 yr were 46.6 ± 7.9 and 39.3 ± 6.5 mL·kg⋅min for males and females, respectively. On average, each age category (10-yr increments) showed a 10% lower V˙O2peak relative to the next younger age category. V˙O2peak values of previous studies were on average 7.5 mL·kg⋅min (20%) lower for males and 6.5 mL·kg⋅min (21%) lower for females. There was strong evidence supporting a positive association between the V˙O2peak (mL·kg⋅min) and the level of habitual PA performed at vigorous PA (estimate, 0.26; P < 0.001]. CONCLUSION: Maximal and submaximal CPET reference values over a large age range are novel, and differences to other studies are clinically highly relevant. Objectively measured vigorous-intensity PA showed a strong positive association with higher V˙O2peak and other performance-related CPET parameters, supporting the implementation of higher-intensity aerobic exercise in health promotion.

Tumor-Associated Macrophages-Implications for Molecular Oncology and Imaging.

Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting in varying membrane receptors and expression of intracellular proteins allow the specific characterization of different subsets of TAMs. Those markers similarly allow tracking of TAMs by different means of molecular imaging. This review aims to provides an overview of the origin of tumor-associated macrophages, their polarization in different subtypes, and how characteristic markers of the subtypes can be used as targets for molecular imaging and theranostic approaches.

Cardiac structure and function in response to a multi-stage marathon over 4486 km.

AIMS: To investigate whether participation in the Trans Europe Foot Race 2009 (TEFR), an ultramarathon race held over 64 consecutive days and 4486 km, led to changes in cardiac structure and function. METHODS: Cardiac magnetic resonance imaging was performed in 20 of 67 participating runners (two women; mean ± SD age 47.8 ± 10.4 years) at three time points (baseline scan at 294 ± 135 km (B), scan two at 1735 ± 86 km (T1) and scan three at 3370 ± 90 km (T2)) during the TEFR. Imaging included an assessment of left ventricular structure (mass) and function (strain). In parallel, cardiac troponin I, NT-pro-BNP, myostatin and GDF11 were determined in venous blood samples. A subsample of ten runners returned for a follow-up scan eight months after the race. RESULTS: Left ventricular mass increased significantly (B, 158.5 ± 23.8 g; T1, 165.1 ± 23.2 g; T2, 167 ± 24.6 g; p < 0.001) over the course of the race, although no significant change was seen in the remaining structural and functional parameters. Serum concentrations of cardiac troponin I and NT-proBNP significantly increased 1.5 - and 3.5-fold, respectively, during the first measurement interval, with no further increase thereafter (cardiac troponin I, 6.8 ± 3.1 (B), 16.9 ± 10.4 (T1) and 17.1 ± 9.7 (T2); NT-proBNP, 30.3 ± 22.8 (B), 135.9 ± 177.5 (T1) and 111.2 ± 87.3 (T2)), whereas the growth markers myostatin and GDF11 did not change. No association was observed with functional parameters, including the ejection fraction and the volume of both ventricles. The follow-up scans showed a reduction to baseline values (left ventricular mass 157 ± 19.3 g). CONCLUSIONS: High exercise-induced cardiac volume load for >2 months in ultra-endurance runners results in a physiological structural adaptation with no sign of adverse cardiovascular remodelling.

Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights.

Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.

Composite Measures of Physical Fitness to Discriminate Between Healthy Aging and Heart Failure: The COmPLETE Study.

BACKGROUND: Aging and changing age demographics represent critical problems of our time. Physiological functions decline with age, often ending in a systemic process that contributes to numerous impairments and age-related diseases including heart failure (HF). We aimed to analyze whether differences in composite measures of physiological function [health distance (HD)], specifically physical fitness, between healthy individuals and patients with HF, can be observed. METHODS: The COmPLETE Project is a cross-sectional study of 526 healthy participants aged 20-91 years and 79 patients with stable HF. Fifty-nine biomarkers characterizing fitness (cardiovascular endurance, muscle strength, and neuromuscular coordination) and general health were assessed. We computed HDs as the Mahalanobis distance for vectors of biomarkers (all and domain-specific subsets) that quantified deviations of individuals' biomarker profiles from "optimums" in the "reference population" (healthy participants aged <40 years). We fitted linear regressions with HD outcomes and disease status (HF/Healthy) and relevant covariates as predictors and logistic regressions for the disease outcome and sex, age, and age2 as covariates in the base model and the same covariates plus combinations of one or two HDs. RESULTS: Nine out of 10 calculated HDs showed evidence for group differences between Healthy and HF (p ≤ 0.002) and most models presented a negative estimate of the interaction term age by group (p < 0.05 for eight HDs). The predictive performance of the base model for HF cases significantly increased by adding HD General health or HD Fitness [areas under the receiver operating characteristic (ROC) curve (AUCs) 0.63, 0.89, and 0.84, respectively]. HD Cardiovascular endurance alone reached an AUC of 0.88. Further, there is evidence that the combination of HDs Cardiovascular endurance and General health shows superior predictive power compared to single HDs. CONCLUSION: HD composed of physical fitness biomarkers differed between healthy individuals and patients with HF, and differences between groups diminished with increasing age. HDs can successfully predict HF cases, and HD Cardiovascular endurance can significantly increase the predictive power beyond classic clinical biomarkers. Applications of HD could strengthen a comprehensive assessment of physical fitness and may present an optimal target for interventions to slow the decline of physical fitness with aging and, therefore, to increase health span.

Effectiveness of a Behavior Change Technique-Based Smartphone Game to Improve Intrinsic Motivation and Physical Activity Adherence in Patients With Type 2 Diabetes: Randomized Controlled Trial.

BACKGROUND: Regular physical activity (PA) is an essential component of a successful type 2 diabetes treatment. However, despite the manifest evidence for the numerous health benefits of regular PA, most patients with type 2 diabetes remain inactive, often due to low motivation and lack of PA enjoyment. A recent and promising approach to help overcome these PA barriers and motivate inactive individuals to change their PA behavior is PA-promoting smartphone games. While short-term results of these games are encouraging, the long-term success in effectively changing PA behavior has to date not been confirmed. It is possible that an insufficient incorporation of motivational elements or flaws in gameplay and storyline in these games affect the long-term motivation to play and thereby prevent sustained changes in PA behavior. We aimed to address these design challenges by developing a PA-promoting smartphone game that incorporates established behavior change techniques and specifically targets inactive type 2 diabetes patients. OBJECTIVE: To investigate if a self-developed, behavior change technique-based smartphone game designed by an interdisciplinary team is able to motivate inactive individuals with type 2 diabetes for regular use and thereby increase their intrinsic PA motivation. METHODS: Thirty-six inactive, overweight type 2 diabetes patients (45-70 years of age) were randomly assigned to either the intervention group or the control group (one-time lifestyle counseling). Participants were instructed to play the smartphone game or to implement the recommendations from the lifestyle counseling autonomously during the 24-week intervention period. Intrinsic PA motivation was assessed with an abridged 12-item version of the Intrinsic Motivation Inventory (IMI) before and after the intervention. In addition, adherence to the game-proposed PA recommendations during the intervention period was assessed in the intervention group via the phone-recorded game usage data. RESULTS: Intrinsic PA motivation (IMI total score) increased significantly in the intervention group (+6.4 (SD 4.2; P<.001) points) while it decreased by 1.9 (SD 16.5; P=.623) points in the control group. The adjusted difference between both groups was 8.1 (95% CI 0.9, 15.4; P=.029) points. The subscales "interest/enjoyment" (+2.0 (SD 1.9) points, P<.001) and "perceived competence" (+2.4 (SD 2.4) points, P<.001) likewise increased significantly in the intervention group while they did not change significantly in the control group. The usage data revealed that participants in the intervention group used the game for an average of 131.1 (SD 48.7) minutes of in-game walking and for an average of 15.3 (SD 24.6) minutes of strength training per week. We found a significant positive association between total in-game training (min) and change in IMI total score (beta=0.0028; 95% CI 0.0007-0.0049; P=.01). CONCLUSIONS: In inactive individuals with type 2 diabetes, a novel smartphone game incorporating established motivational elements and personalized PA recommendations elicits significant increases in intrinsic PA motivation that are accompanied by de-facto improvements in PA adherence over 24 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT02657018; https://clinicaltrials.gov/ct2/show/NCT02657018.

Which Cutoffs for Secondary V˙O2max Criteria Are Robust to Diurnal Variations?

PURPOSE: The aim was to determine the minimum maximum oxygen uptake (V˙O2max) criteria cut-offs in highly trained athletes (i.e., maximum RER [RERmax], maximum HR [HRmax], maximum RPE [RPEmax], and maximum blood lactate concentration [BLmax]) necessary to determine maximum oxygen uptake (V˙O2max) during cardiopulmonary exercise tests (CPET), by balancing type I and type II errors. A further aim was to investigate if the defined cutoffs would be robust to diurnal and to day-to-day variations. METHODS: Data from two CPET studies involving young athletes were analyzed. In the first study, 70 male participants performed one CPET until exhaustion to define cutoffs. In the second study, eight males and five females performed one CPET on seven consecutive days at six different times of day (i.e., diurnal variation). The time of the CPET was identical on the sixth and seventh days (i.e., day-to-day variation). To ensure comparability both studies were carried out under the same conditions. RESULTS: Participants' mean V˙O2max was 63.0 ± 5.3 mL·kg·min. RERmax ≥1.10 was reached by 100%, HRmax ≥95% of age-predicted HRmax by 99%, RPEmax ≥19 by 100%, and BLmax ≥8 mmol·L by 100% of participants, respectively. Regarding the intraday variations, latter cutoffs were not reached in two cases for RERmax and in one case for HRmax and BLmax. Intraclass correlations for the day-to-day variability were r = 0.823 for RERmax, r = 0.828 for HRmax, and r = 0.380 for BLmax, respectively. CONCLUSIONS: The proposed high cut-off values for secondary criteria provide some assurance that V˙O2max may have been achieved in athletes without increasing type II errors. However, type I errors may still occur indicating that further methods such as V˙O2-plateau or V˙O2-validation may be required.

Novel Smartphone Game Improves Physical Activity Behavior in Type 2 Diabetes.

INTRODUCTION: Many type 2 diabetes patients show insufficient levels of physical activity and are often unmotivated to change physical activity behaviors. This study investigated whether a newly developed smartphone game delivering individualized exercise and physical activity promotion through an elaborate storyline can generate sustained improvements in daily physical activity (steps/day). STUDY DESIGN: Thirty-six participants were enrolled in this 24-week RCT between August 2016 and April 2018. After baseline assessment, participants were randomized in equal numbers to the intervention or control condition. Data analysis was performed in May-June 2018. SETTING/PARTICIPANTS: Inactive, overweight type 2 diabetes patients, aged 45-70 years, were recruited through advertising and from hospitals and diabetes care centers in the Basel, Switzerland, metropolitan area. INTERVENTION: Participants were instructed to play the innovative smartphone game (intervention group) or to implement the recommendations from the baseline lifestyle counseling (control group) autonomously during the 24-week intervention period. MAIN OUTCOME MEASURES: Primary outcomes were changes in daily physical activity (steps/day); changes in aerobic capacity, measured as oxygen uptake at the first ventilatory threshold; and changes in glycemic control, measured as HbA1c. RESULTS: Daily physical activity increased by an average of 3,998 (SD=1,293) steps/day in the intervention group and by an average of 939 (SD=1,156) steps/day in the control group. The adjusted difference between the two groups was 3,128 steps/day (95% CI=2,313, 3,943, p<0.001). The increase in daily physical activity was accompanied by an improved aerobic capacity (adjusted difference of oxygen uptake at the first ventilatory threshold of 1.9 mL/(kg·min), 95% CI=0.9, 2.9, p<0.001). Glycemic control (HbA1c) did not change over the course of the intervention. CONCLUSIONS: A novel, self-developed smartphone game, delivering multidimensional home-based exercise and physical activity promotion, significantly increases daily physical activity (steps/day) and aerobic capacity in inactive type 2 diabetes patients after 24 weeks. The ability of the game to elicit a sustained physical activity motivation may be relevant for other inactive target groups with chronic diseases. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02657018.