Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

High-intensity intermittent training is as effective as moderate continuous training, and not deleterious, in cardiomyocyte remodeling of hypertensive rats.

Exercise training offers possible nonpharmacological therapy for cardiovascular diseases including hypertension. High-intensity intermittent exercise (HIIE) training has been shown to have as much or even more beneficial cardiovascular effect in patients with cardiovascular diseases than moderate-intensity continuous exercise (CMIE) training. The aim of this study was to investigate the effects of the two types of training on cardiac remodeling of spontaneously hypertensive rats (SHR) induced by hypertension. Eight-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were divided into four groups: normotensive and hypertensive control (WKY and SHR-C) and hypertensive trained with CMIE (SHR-T CMIE) or HIIE (SHR-T HIIE). After 8 wk of training or inactivity, maximal running speed (MRS), arterial pressure, and heart weight were all assessed. CMIE or HIIE protocols not only increased final MRS and left ventricular weight/body weight ratio but also reduced mean arterial pressure compared with sedentary group. Then, left ventricular tissue was enzymatically dissociated, and isolated cardiomyocytes were used to highlight the changes induced by physical activity at morphological, mechanical, and molecular levels. Both types of training induced restoration of transverse tubule regularity, decrease in spark site density, and reduction in half-relaxation time of calcium transients. HIIE training, in particular, decreased spark amplitude and width, and increased cardiomyocyte contractility and the expression of sarco(endo)plasmic reticulum Ca2+-ATPase and phospholamban phosphorylated on serine 16. NEW & NOTEWORTHY High-intensity intermittent exercise training induces beneficial remodeling of the left ventricular cardiomyocytes of spontaneously hypertensive rats at the morphological, mechanical, and molecular levels. Results also confirm, at the cellular level, that this type of training, as it appears not to be deleterious, could be applied in rehabilitation of hypertensive patients.

Reliability of Peak Exercise Stroke Volume Assessment by Impedance Cardiography in Patients with Residual Right Outflow Tract Lesions After Congenital Heart Disease Repair.

Global ventricular response to exercise may be useful in follow-up of patients with residual right outflow tract lesions after congenital heart disease repair. In this context, impedance cardiography is considered accurate for stroke volume (SV) measurement during exercise testing, however, to date, only partial assessment of its reliability has been reported. We retrospectively evaluated relative and absolute reliability of peak SV by impedance cardiography during exercise using intraclass correlation (ICC) and standard error of measurement (SEM) in this population. Peak SV was measured in 30 young patients (mean age 14.4 years ± 2.1) with right ventricular outflow tract reconstruction who underwent two cardiopulmonary exercise tests at a mean one-year interval. SV was measured using a signal morphology impedance cardiography analysis device (PhysioFlow®) and was indexed to body surface area. ICC of peak indexed SV measurement was 0.80 and SEM was 10.5%. High heterogeneity was seen when comparing patients according to peak indexed SV; in patients with peak SV < 50 ml/m2 (15 patients), ICC rose to 0.95 and SEM dropped to 2.7%, while in patients with a peak SV > 50 ml/m2 relative and absolute reliability decreased (ICC = 0.45, SEM = 12.2%). Peak exercise SV assessment by a PhysioFlow® device represents a highly reliable method in patients with residual right outflow tract lesions after congenital heart disease repair, especially in patients with peak SV < 50 ml/m2. In this latter group, a peak SV decrease > 7.3% (corresponding to the minimum "true" difference) should be considered a clinically-relevant decrease in global ventricular performance and taken into account when deciding whether to perform residual lesion removal.

The ambulatory hypotensive effect of aerobic training: a reappraisal through a meta-analysis of selected moderators.

The effectiveness of regular exercise in decreasing both systolic and diastolic blood pressure (BP) is well-established. Our purpose was to assess the impact of both subject and physical activity program characteristics on ambulatory BP through a meta-analysis of the existing literature. Three databases (PubMed, Embase, Web of Science) were searched using relevant terms and strategies. From 637 identified records, 37 studies met inclusion criteria: details about training intervention and participant characteristics, pre- and post-training ambulatory BP measurements, at home (HBPM) or during 24-h (ABPM). The weighted mean difference was for 24-h systolic/diastolic ABPM (n = 847 participants): -4.06/-2.77 mmHg (95%CI: -5.19 to -2.93/-3.58 to -1.97; P < 0.001), for daytime (ABPM or HBPM, n = 983): -3.78/-2.73 mmHg (95%CI: -5.09 to -2.47/-3.57 to -1.89; P < 0.001) and nighttime ABPM periods (n = 796): -2.35/-1.70 mmHg (95%CI: -3.26 to -1.44/-2.45 to -0.95; P < 0.001). Characteristics significantly influencing BP improvement were: an initial office BP ≥130/85 mmHg and diet-induced weight-loss. We found no differences according to sex, age, or training characteristics (intensity, number of sessions, training duration). Antihypertensive effects of aerobic training assessed by ambulatory BP measurements appear significant and clinically relevant for both daytime and nighttime periods, in particular for participants with an office BP ≥130/85 mmHg.

Physiological Interpretation of the Slope during an Isokinetic Fatigue Test.

To assess the relationship between selected measures (the slope and average performance) obtained during a high intensity isokinetic fatigue test of the knee (FAT) and relevant measures of anaerobic and aerobic capacities. 20 well-trained cyclists performed 3 randomly ordered sessions involving a FAT consisting in 30 reciprocal maximal concentric contractions of knee flexors and extensors at 180°.s(-1), a maximal continuous graded exercise test (GXT), and a Wingate anaerobic test (WAnT). The slope calculated from peak torque (PT) and total work (TW) of knee extensors was highly associated to maximal PT (r=-0.86) and maximal TW (r=-0.87) measured during FAT, and moderately associated to peak power output measured during the WAnT (r=-0.64 to -0.71). Average PT and average TW were highly associated to maximal PT (r=0.93) and maximal TW (r=0.96), to mean power output measured during WAnT (r=0.83-0.90) and moderately associated to maximal oxygen uptake (0.58-0.67). In conclusion, the slope is mainly determined by maximal anaerobic power, while average performance is a composite measure depending on both aerobic and anaerobic energy systems according to proportions that are determined by the duration of the test.

Are first ventilatory threshold and 6-minute walk test heart rate interchangeable? A pilot study in healthy elderlies and cardiac patients.

BACKGROUND: Heart rate (HR) at the ventilatory threshold (VT) is often used to prescribe exercise intensity in cardiac rehabilitation. Some studies have reported no significant difference between HR at VT and HR measured at the end of a 6-min walk test (6-MWT) in cardiac patients. The aim of this work was to assess the potential equivalence between those parameters at the individual level. METHOD: Three groups of subjects performed a stress test and a 6-MWT: 22 healthy elderlies (GES, 77 ± 3.7 years), 10 stable coronary artery disease (CAD) patients (GMI, 50.9 ± 4.2 years) and 30 patients with chronic heart failure (GHF, 63.3 ± 10 years). We analyzed the correlation, mean bias, 95% confidence interval (95% CI) of the mean bias and the magnitude of the bias between 6-MWT-HR and VT-HR. RESULTS: There was a significant difference between 6-MWT and VT-HR in GHF (99.1 ± 8.8 vs 91.6 ± 18.6 bpm, P=0.016) but not in GES and GMI. The correlation between those 2 parameters was high for GMI (r=0.78, P<0.05), and moderate for GES and GHF (r=0.48 and 0.55, respectively, P<0.05). The 95% CI of bias was large (>30%) in GES and GHF and acceptable in GMI (8-12%). CONCLUSION: 6-MWT-HR and VT-HR do not appear interchangeable at the individual level in healthy elderlies and CHF patients. In CAD patients, further larger studies and/or the development of other walk tests could help in confirming the interest of a training prescription based on walking performance, after an exhaustive study of their cardiometabolic requirements.

[High blood pressure and physical exercise]. / Hypertension artérielle et exercice physique - Mise au point pratique.

High blood pressure is a frequent pathology with many cardiovascular complications. As highlighted in guidelines, the therapeutic management of hypertension relies on non-pharmacological measures, which are diet and regular physical activity, but both patients and physicians are reluctant to physical activity prescription. To acquire the conviction that physical activity is beneficial, necessary and possible, we can take into account some fundamental and clinical studies, as well as the feedback of our clinical practice. Physical inactivity is a major risk factor for cardiovascular morbidity and mortality, and hypertension contributes to increase this risk. Conversely, regular practice of physical activity decreases very significantly the risk by up to 60%. The acute blood pressure changes during exercise and post-exercise hypotension differs according to the dynamic component (endurance or aerobic and/or strength exercises), but the repetition of the sessions leads to the chronic hypotensive benefit of physical activity. Moreover, physical activity prescription must take into account the assessment of global cardiovascular risk, the control of the hypertension, and the opportunities and desires of the patient in order to promote good adherence and beneficial lifestyle change.

Effect of overreaching on cognitive performance and related cardiac autonomic control.

The purpose of this study was to characterize the effect of a 2-week overload period immediately followed by a 1-week taper period on different cognitive processes including executive and nonexecutive functions, and related heart rate variability. Eleven male endurance athletes increased their usual training volume by 100% for 2 weeks, and decreased it by 50% for 1 week. A maximal graded test, a constant speed test at 85% of peak treadmill speed, and a Stroop task with the measurement of heart rate variability were performed at each period. All participants were considered as overreached. We found a moderate increase in the overall reaction time to the three conditions of the Stroop task after the overload period (816 ± 83 vs 892 ± 117 ms, P = 0.03) followed by a return to baseline after the taper period (820 ± 119 ms, P = 0.013). We found no association between cognitive performance and cardiac parasympathetic control at baseline, and no association between changes in these measures. Our findings clearly underscore the relevance of cognitive performance in the monitoring of overreaching in endurance athletes. However, contrary to our hypothesis, we did not find any relationship between executive performance and cardiac parasympathetic control.

Locomotor performance in highly-trained young soccer players: does body size always matter?

To examine the effects of body size on locomotor performance, 807 15-year-old French and 64 Qatari soccer players participated in the present study. They performed a 40-m sprint and an incremental running test to assess maximal sprinting (MSS) and aerobic speeds, respectively. French players were advanced in maturity, taller, heavier, faster and fitter than their Qatari counterparts (e.g., Cohen's d=+1.3 and + 0.5 for body mass and MSS). However, when adjusted for body mass (BM), Qatari players had possibly greater MSS than French players (d=+0.2). A relative age effect was observed within both countries, with the players born in the first quarter of the year being taller, heavier and faster that those born during the fourth quarter (e.g., d=+0.2 for MSS in French players). When directly adjusted for BM, these MSS differences remained (d=+0.2). Finally, in both countries, players selected in National teams were taller, heavier, faster and fitter than their non-selected counterparts (e.g., d=+0.6 for MSS in French players), even after adjustments for body size (d=+0.5). Differences in locomotor performances between players with different phenotypes are likely mediated by differences in body size. However, when considering more homogeneous player groups, body dimensions are unlikely to substantially explain the superior locomotor performances of older and/or international players.

Effect of training cessation on muscular performance: a meta-analysis.

The purpose of this study was to assess the effect of resistance training cessation on strength performance through a meta-analysis. Seven databases were searched from which 103 of 284 potential studies met inclusion criteria. Training status, sex, age, and the duration of training cessation were used as moderators. Standardized mean difference (SMD) in muscular performance was calculated and weighted by the inverse of variance to calculate an overall effect and its 95% confidence interval (CI). Results indicated a detrimental effect of resistance training cessation on all components of muscular performance: [submaximal strength; SMD (95% CI) = -0.62 (-0.80 to -0.45), P < 0.01], [maximal force; SMD (95% CI) = -0.46 (-0.54 to -0.37), P < 0.01], [maximal power; SMD (95% CI) = -0.20 (-0.28 to -0.13), P < 0.01]. A dose-response relationship between the amplitude of SMD and the duration of training cessation was identified. The effect of resistance training cessation was found to be larger in older people (> 65 years old). The effect was also larger in inactive people for maximal force and maximal power when compared with recreational athletes. Resistance training cessation decreases all components of muscular strength. The magnitude of the effect differs according to training status, age or the duration of training cessation.

Carbon and nitrogen partitioning during the post-anthesis period is conditioned by N fertilisation and sink strength in three cereals.

Further knowledge of the processes conditioning nitrogen use efficiency (NUE) is of great relevance to crop productivity. The aim of this paper was characterise C and N partitioning during grain filling and their implications for NUE. Cereals such as bread wheat (Triticum aestivum L. cv Califa sur), triticale (× Triticosecale Wittmack cv. Imperioso) and tritordeum (× Tritordeum Asch. & Graebn line HT 621) were grown under low (LN, 5 mm NH(4) NO(3)) and high (HN, 15 mm NH(4)NO(3)) N conditions. We conducted simultaneous double labelling ((12)CO(2) and (15)NH(4) (15)NO(3)) in order to characterise C and N partitioning during grain filling. Although triticale plants showed the largest total and ear dry matter values in HN conditions, the large investment in shoot and root biomass negatively affected ear NUE. Tritordeum was the only genotype that increased NUE in both N treatments (NUE(total)), whereas in wheat, no significant effect was detected. N labelling revealed that N fertilisation during post-anthesis was more relevant for wheat and tritordeum grain filling than for triticale. The study also revealed that the investments of C and N in flag leaves and shoots, together with the 'waste' of photoassimilates in respiration, conditioned the NUE of plants, and especially under LN. These results suggest that C and N use by these plants needs to be improved in order to increase ear C and N sinks, especially under LN. It is also remarkable that even though tritordeum shows the largest increase in NUE, the low yield of this cereal limits its agronomic value.

Accelerometer as a tool to assess sedentarity and adherence to physical activity recommendations after cardiac rehabilitation program.

PURPOSE: To objectively assess, in stable cardiac patients, the adherence to physical activity (PA) recommendations using an accelerometer at 2 or 12 months after the discharge of cardiac rehabilitation program (CRP). METHODS: Eighty cardiac patients wore an accelerometer at 2 months (group 1, short-term adherence, n = 41) or one-year (group 2, long-term adherence, n = 39) after a CRP including therapeutic education about regular PA. PA was classified as "light" (1.8-2.9 Metabolic Equivalent of Task [METs]), "moderate" (3-5.9 METs), or "intense" (>6 METs). Energy expenditure (EE, in Kcal) and time (min) spent in these three different levels were measured during a one-week period with the MyWellness Key actimeter (MWK). Motivational readiness for change was also assessed at the end of CRP. Patients were considered as physically active when a minimum of 150 min of moderate PA during the one-week period was achieved. RESULTS: Both groups were comparable, except for exercise capacity at the end of the CRP which was slightly higher in group 1 (167.5 ± 42.3 versus 140.7 ± 46.1 W, P < 0.01). The total weekly active EE averaged 676.7 ± 353.2 kcal and 609.5 ± 433.5 kcal in group 1 and 2, respectively. The time spent within the light-intensity range PA was 319.4 ± 170.9 and 310.9 ± 160.6 min, and the time spent within the moderate-intensity range averaged 157.4 ± 115.4 and 165 ± 77.2 min per week for group 1 and 2, respectively. Fifty-three percent and 41% of patients remained active in both groups respectively. CONCLUSION: About half of the patients are non-adherent to PA after CRP and do not reach target levels recommended by physicians. The first 2 months following the discharge of CRP seem to be of outmost importance for lifestyle modifications maintenance, and further study monitoring more closely PA decrease could help to clarify the optimal follow-up options.

VO2 slow component is independent from critical power.

The aim of this study was to determine whether the amplitude of the V˙O (2) slow component was dependent from Critical Power (CP; the slope of the linear time - distance relationship) in individuals matched for V˙O (2) peak. 30 moderately-trained endurance athletes completed a maximal graded exercise test, 2 randomly ordered constant power tests at 90 and 100% of peak power output (PPO), and 2 constant duration test of 6 min at 30% of the difference between CP and PPO. Afterwards, participants were ranked according to their relative CP (%PPO; a direct measure of aerobic endurance). The median third was excluded to form a low aerobic endurance group (LEG) and a high aerobic endurance group (HEG). A t-test revealed no difference between LEG and HEG in peak oxygen consumption, but a large difference in their relative CP (p<0.001, effect size=3.2). A' (2) was similar between groups (626 ± 96 and 512 ± 176 ml, corresponding to 26 ± 4 and 24 ± 8% of end exercise oxygen consumption, respectively; NS) and was not associated with relative CP (r=0.10; NS). These results suggest that increasing CP probably extends the range of exercise intensities over which the V˙O (2) slow component does not develop, but does not decrease the amplitude of this phenomenon once it occurs.

Effect of functional overreaching on executive functions.

The aim of this study was to investigate whether cognitive performance was a valid marker of overreaching. 10 well-trained male endurance athletes increased their training load by 100% for 2 weeks. They performed a maximal graded test, a constant speed test, a reaction time task and a computerized version of the Stroop color word-test before and after this overload period. Regarding performance results, five participants were considered as overreached and the five remaining were considered as well-trained. We found no significant differences between groups in performing the Stroop test. Noteworthy, we found a small increase in response time in the more complex condition in overreached athletes (1 188+/-261 to 1 297+/-231 ms, effect size=0.44), while it decreased moderately in the well-trained athletes (1 066+/-175 to 963+/-171 ms, effect size=-0.59). Furthermore, we found an interaction between time and group on initiation time of the reaction time task, since it increased in overreached athletes after the overload period (246+/-24 to 264+/-26 ms, p<0.05), while it remained unchanged in well-trained participants. Participants made very few anticipation errors, whatever the group or the period (error rate <2%).We concluded that an unaccustomed increase in training volume which is accompanied by a decrement in physical performance induces a deterioration of some executive functions.

Effect of the lengthening of the protocol on the reliability of muscle fatigue indicators.

The aim of this study was to examine absolute and relative reliability of fatigue measures calculated from peak torque or total work during 20, 30, 40 and 50 reciprocal maximal concentric contractions performed on an isokinetic dynamometer at 180 degrees x s(-1). Eighteen moderately active men performed 50 reciprocal maximal concentric contractions on three occasions with one 7-10 days recovery between each session. Peak torque and total work were computed for each contraction and subsequently summed to compute cumulated performance after respectively 20, 30, 40 and 50 repetitions. Muscle fatigue was determined after 20, 30, 40 and 50 repetitions by the fatigue index, the percent decrease in performance and the slope. Reliability of average peak torque or average total work was similar and was not affected by the lengthening of the protocol, although a learning effect was evident for knee flexors. Reliability of fatigue measures calculated from peak torque or total work was similar, improved with the lengthening of the protocol and was better for knee extensors. Measuring average peak torque or average total work and the slope during a protocol involving 30 maximal reciprocal concentric contractions appear to represent a better compromise between reliability and physiological interpretability of the data.

Anaerobic Work Capacity derived from isokinetic and isoinertial cycling.

The purpose of this study was to compare Anaerobic Work Capacity (AWC) measured on an isoinertial or an isokinetic bicycle ergometer. Twelve male participants completed two randomly ordered exercise testing sessions including a torque-velocity test followed by a 30-s all-out test on an isokinetic ergometer, or a force-velocity test followed by a Wingate Anaerobic Test on an isoinertial ergometer. Optimal load measured during the force-velocity test on the isoinertial ergometer was 1.13+/-0.11 N.kg(-1). Optimal cadence measured during the torque-velocity test on the isokinetic ergometer was 107+/-13 rpm. Although P(peak) measures were significantly correlated (r=0.77), we found a large difference between them (effect size=2.85) together with wide limits of agreement (bias+/-95%LOA=24+/-12%). The same observation was made with P(mean), but with a smaller magnitude of difference (bias+/-95%LOA=4.2+/-12%; effect size=0.51; r=0.73). This lack of agreement led us to the conclusion that AWC measures obtained during 30-s all-out tests performed on an isoinertial or an isokinetic bicycle ergometer are not necessarily similar and cannot be used interchangeably.

[Treatment of venous thromboembolic disease in cancer patients]. / Traitement de la maladie thromboembolique veineuse chez le cancéreux.

Venous thromboembolism (VTE) disease, as defined by the occurrence of deep venous thrombosis or pulmonary embolism, occurs among 4 to 20% of patients with cancer and is a leading cause of death among these patients. Use of classical anticoagulation to treat VTE in a cancer patient is associated with a higher risk of major bleeding and of VTE recurrence as compared to noncancer patients. Updated comprehensive and systematic review of current data from the medical literature allows to reconsider the classical approach used for anticoagulant treatment in cancer patients and to implement adapted recommendations. In 2008, the use of daily subcutaneous low-molecular-weight heparin (LMWH) for at least three to six months is recommended as first line therapy to treat VTE disease in cancer patients. If LMWH are contra-indicated (renal insufficiency), other therapeutic approaches are warranted, such as use of unfractionated heparin (UFH) with early introduction of anti-vitamin K for at least three months or venous cava filter in case of absolute contra-indications to anticoagulation. VTE prophylaxis in cancer patients relies on the same therapeutic approaches as currently used for noncancer patients at high risk of VTE. The definition of more specific prophylactic approaches for patients with cancer considered at higher risks of VTE, will be the subject of many clinical trials in the forthcoming years.

Is heart rate a convenient tool to monitor over-reaching? A systematic review of the literature.

OBJECTIVE: A meta-analysis was conducted on the effect of overload training on resting HR, submaximal and maximal exercise HR (HR), and heart rate variability (HRV), to determine whether these measures can be used as valid markers of over-reaching. METHODS: Six databases were searched using relevant terms and strategies. Criteria for study inclusion were: participants had to be competitive athletes, an increased training load intervention had to be used, and all necessary data to calculate effect sizes had to be available. An arbitrary limit of 2 weeks was chosen to make the distinction between short-term and long-term interventions. Dependent variables were HR and HRV (during supine rest). Standardised mean differences (SMD) in HR or HRV before and after interventions were calculated, and weighted according to the within-group heterogeneity to develop an overall effect. RESULTS: In these competitive athletes, short-term interventions resulted in a moderate increase in both resting HR (SMD = 0.55; p = 0.01) and low frequency/high frequency ratio (SMD = 0.52; p = 0.02), and a moderate decrease in maximal HR (SMD = -0.75; p = 0.01). Long-term interventions resulted in a small decrease in HR during submaximal (SMD = -0.38; p = 0.006) and maximal exercise (SMD = -0.33; p = 0.007), without alteration of resting values. CONCLUSION: The small to moderate amplitude of these alterations limits their clinical usefulness, as expected differences may fall within the day-to-day variability of these markers. Consequently, correct interpretation of HR or HRV fluctuations during the training process requires the comparison with other signs and symptoms of over-reaching to be meaningful.