Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial.

BACKGROUND: There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer. METHODS: A prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery. RESULTS: Comparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1-3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed. CONCLUSION: The results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic. TRIAL REGISTRATION NUMBER: NCT03626610.

Charter to establish clinical exercise physiology as a recognised allied health profession in the UK: a call to action.

The UK population is growing, ageing and becoming increasingly inactive and unfit. Personalised and targeted exercise interventions are beneficial for ageing and the management of chronic and complex conditions. Increasing the uptake of effective exercise and physical activity (PA) interventions is vital to support a healthier society and decrease healthcare costs. Current strategies for exercise and PA at a population level mostly involve self-directed exercise pathways, delivered largely via the fitness industry. Even for those who opt-in and manage to achieve the current recommendations regarding minimum PA, this generic 'one-size-fits-all' approach often fails to demonstrate meaningful physiological and health benefits. Personalised exercise prescription and appropriate exercise testing, monitoring and progression of interventions for individuals with chronic disease should be provided by appropriately trained and recognised exercise healthcare professionals, educated in the cognate disciplines of exercise science (eg, physiology, biomechanics, motor control, psychology). This workforce has operated for >20 years in the Australian public and private healthcare systems. Accredited exercise physiologists (AEPs) are recognised allied health professionals, with demonstrable health and economic benefits. AEPs have knowledge of the risks and benefits of distinct forms of exercise, skills in the personalised prescription and optimal delivery of exercise, and competencies to support sustained PA behavioural change, based on the established scientific evidence. In this charter, we propose a road map for the training, accreditation and promotion of a clinical exercise physiology profession in the UK.

Medical encounters at community-based physical activity events (parkrun) in the UK.

OBJECTIVE: To determine the incidence, clinical correlates and exposure risk of medical encounters during community-based physical activity events in the UK. METHODS: An analysis of medical data from weekly, community-based physical activity events (parkrun) at 702 UK locations over a 6-year period (29 476 294 participations between 2014 and 2019) was conducted in order to define the incidence and clinical correlates of serious life-threatening, non-life-threatening and fatal medical encounters. RESULTS: 84 serious life-threatening encounters (overall incidence rate=0.26/100 000 participations) occurred including 18 fatalities (0.056/100 000 participations). Statistical modelling revealed that the probabilities of serious life-threatening encounters were exceptionally low, however, male sex, increasing age, slower personal best parkrun time and less prior running engagement/experience (average number of runs per year and number of years as a parkrun participant) were associated with increased probability of serious life-threatening encounters. These were largely accounted for by cardiac arrest (48/84, 57%) and acute coronary syndromes (20/84, 24%). Non-life-threatening medical encounters were mainly attributed to tripping or falling, with a reported incidence of 39.2/100 000 participations. CONCLUSIONS: Serious life-threatening and fatal medical encounters associated with parkrun participation are extremely rare. In the context of a global public health crisis due to inactivity, this finding underscores the safety and corollary public health value of community running/walking events as a strategy to promote physical activity.

Systematic review and meta-analysis of training mode, imaging modality and body size influences on the morphology and function of the male athlete's heart.

CONTEXT: The athlete's heart (AH) remains a popular topic of study. Controversy related to training-specific cardiac adaptation in male athletes, and continuing developments in imaging technology and scaling prompted this systematic review and meta-analysis. OBJECTIVE: To provide new insight in relation to: 1) cardiac adaptation to divergent training patterns in male athletes, 2) a developing research database using cardiac magnetic resonance (CMR) in athletes; 3) functional data derived from tissue-Doppler analysis as well as right ventricular (RV) and left atrial (LA) measurements in athletes; and 4) an awareness of the impact of body size on cardiac dimensions. STUDY DESIGN: Systematic review and meta-analysis of prospective trials. Data extraction performed by two researchers. DATA SOURCES: Pub Med, Medline, Scopus and ISI Web of knowledge scholarly data base. STUDY SELECTION: Prospective studies were included if they were echocardiographic or CMR trials of elite young male athletes, with clear indication of type of sports and passed a quality criteria checklist. RESULTS: All left ventricular (LV) structural parameters were higher in athletes than in controls. Only LV end-diastolic diameter and volume were higher in endurance athletes than in resistance athletes: 54.8 mm (95% CI 54.1 to 55.6) vs 52.4 mm (95% CI 51.2 to 53.6); p<0.001 and 171 ml (95% CI 157 to 185) vs 131 ml (95% CI 120 to 142); p<0.001, respectively. RV end-diastolic volume, mass and LA diameter were higher in endurance athletes than controls. LV end-diastolic volume was larger when CMR was used rather than echocardiography: 178 ml (95% CI Q7 162 to 194) vs 135 ml (95% CI 128 to 142); p<0.001. Meta-analysis regression models demonstrated positive and significant associations between body surface area (BSA) and LV mass, RV mass and LA diameter. CONCLUSIONS: Morphological features of the male AH were noted in both athlete groups. A training-specific pattern of concentric hypertrophy was not discerned in resistance athletes. Both imaging mode and BSA can have a significant impact on the interpretation of AH data.

The endurance athletes heart: acute stress and chronic adaptation.

The impact of endurance exercise training on the heart has received significant research and clinical attention for well over a century. Despite this, many issues remain controversial and clinical interpretation can be complex of biomarkers of cardiomyocyte insult. This review assesses the current state of knowledge related to two areas of research where problems with clinical decision making may arise: (1) the impact of chronic endurance exercise training on cardiac structure, function and electrical activity to the point where the athletic heart phenotype may be similar to the expression of some cardiac pathologies (a diagnostic dilemma referred to as the 'grey-zone') and (2) the impact of acute bouts of prolonged exercise on cardiac function and the presentation of biomarkers and cardiomyocyte insult in the circulatory system. The combination of acute endurance exercise stress on the heart and prolonged periods of training are considered together in the final section.

Conduit diameter and wall remodeling in elite athletes and spinal cord injury.

PURPOSE: This study aimed to investigate localized and systemic effects of chronic exercise and inactivity on conduit artery remodeling in humans. METHODS: We recruited elite athletes engaged in predominantly lower limb (LL runners/cyclists, n = 10) or upper limb (UL canoe paddlers, n = 12) exercise and matched able-bodied, recreationally active, controls (C, n = 16). We also studied wheelchair controls (spinal cord injury, n = 9) and athletes (spinal cord injury, n = 1; spina bifida, n = 4). Carotid, brachial, and superficial femoral (SF) artery diameter and wall thickness were assessed using high-resolution ultrasound. RESULTS: Brachial diameters were significantly larger in UL and wheelchair users (athletes and controls) compared with C (both P < 0.05). SF artery diameter in wheelchair controls was significantly smaller compared with the other groups, with LL athletes having significantly greater lumen diameter than controls (both P < 0.05). In all arteries, a lower wall thickness was found in able-bodied athletes compared with C, including wheelchair athletes compared with wheelchair controls (P < 0.001). In the SF artery, wall-to-lumen-ratio was significantly lower in able-bodied athletes and higher in wheelchair controls compared with able-bodied controls (P < 0.001). In the brachial and carotid arteries, able-bodied and wheelchair athletes demonstrated lower wall-to-lumen-ratio than less active wheelchair controls and able-bodied controls (P < 0.001). CONCLUSIONS: These findings suggest that remodeling of the arterial wall occurs systemically in response to exercise training and is unrelated to exercise type in humans. Conversely, localized effects are evident with respect to the effect of exercise on arterial diameter. These findings have implications for our understanding of the effects of exercise on arterial structure and function in humans.

Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise.

Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.

Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies.

OBJECTIVE: To evaluate the risk of chronic traumatic brain injury from amateur boxing. SETTING: Secondary research performed by combination of sport physicians and clinical academics. DESIGN, DATA SOURCES, AND METHODS: Systematic review of observational studies in which chronic traumatic brain injury was defined as any abnormality on clinical neurological examination, psychometric testing,neuroimaging studies, and electroencephalography. Studies were identified through database (1950 to date) and bibliographic searches without language restrictions. Two reviewers extracted study characteristics, quality, and data, with adherence to a protocol developed from a widely recommended method for systematic review of observational studies (MOOSE). RESULTS: 36 papers had relevant extractable data (from a detailed evaluation of 93 studies of 943 identified from the initial search). Quality of evidence was generally poor. The best quality studies were those with a cohort design and those that used psychometric tests. These yielded the most negative results: only four of 17 (24%) better quality studies found any indication of chronic traumatic brain injury in a minority of boxers studied. CONCLUSION: There is no strong evidence to associate chronic traumatic brain injury with amateur boxing.

Changes in vascular and cardiac function after prolonged strenuous exercise in humans.

Prolonged exercise has been shown to result in an acute depression in cardiac function. However, little is known about the effect of this type of exercise on vascular function. Therefore, the purpose of the present study was to investigate the impact of an acute bout of prolonged strenuous exercise on vascular and cardiac function and the appearance of biomarkers of cardiomyocyte damage in 15 male (32 +/- 10 yr) nonelite runners. The subjects were tested on two occasions, the day before and within an hour of finishing the London marathon (229 +/- 38 min). Function of the brachial and femoral arteries was determined using flow-mediated dilatation (FMD). Echocardiographic assessment of cardiac strain, strain rate, tissue velocities, and flow velocities during diastole and systole were also obtained. Venous blood samples were taken for later assessment of cardiac troponin I (cTnI), a biomarker of cardiomyocyte damage. Completion of the marathon resulted in a depression in femoral (P = 0.04), but not brachial (P = 0.96), artery FMD. There was no change, pre- vs. postmarathon, in vascular shear, indicating that the impaired femoral artery function was not related to hemodynamic changes. The ratio of peak early to atrial radial strain rate, a measure of left ventricular diastolic function, was reduced postmarathon (P = 0.006). Postrace cTnI was elevated in 12 of 13 runners, with levels above the recognized clinical threshold for damage in 7 of these. In conclusion, when taken together, these data suggest a transient depression in cardiac and leg vascular function following prolonged intensive exercise.

Senescent T-lymphocytes are mobilised into the peripheral blood compartment in young and older humans after exhaustive exercise.

Senescent T-lymphocytes are antigen-experienced cells that express the killer-cell lectin-like receptor G1 (KLRG1) and/or CD57; fail to clonally expand following further antigenic stimulation and prevail in the resting blood of older adults compared to the young. Physical exercise mobilises T-lymphocytes into the bloodstream and is therefore a model with which to compare age-related phenotypes of blood-resident T-cells with those T-cells entering the blood from peripheral lymphoid compartments. Eight young (Y; Age: 21+/-3 years) and 8 older (O; Age: 56+/-3 years) healthy males completed a maximal treadmill exercise protocol. Blood lymphocytes isolated before, immediately after and 1h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L and lymphocyte subset markers using three-colour flow cytometry. Lymphocyte subset numbers (CD3+, CD3+/CD4+, CD3+/CD8 and CD3-/CD56+) increased with exercise (p<0.05) but were not different between Y and O. At rest and immediately after exercise, the percentage of CD3+/CD8+ T-lymphocytes expressing KLRG1 and CD45RO was greater in O than Y, whereas Y had a greater expression of CD45RA and CD62L than O. The percentage of all CD3+/CD8+ and CD3+/CD4+ T-lymphocytes expressing KLRG1 and CD57 increased after exercise, but the magnitude of change was not age-dependent. In conclusion, there is a greater proportion of senescent CD3+/CD8+ T-lymphocytes in the blood of older adults compared to young at rest and immediately after exhaustive exercise, indicating that the greater frequency of KLRG1+/CD8+ T-lymphocytes in older humans is ubiquitous and not localised to the peripheral blood.

Apoptosis does not contribute to the blood lymphocytopenia observed after intensive and downhill treadmill running in humans.

The lymphocytopenia that occurs during the recovery stage of exercise may be a result of apoptosis through an increased expression of CD95, a loss of the complement regulatory proteins CD55 and CD59, or both. Trained subjects completed intensive, moderate, and downhill treadmill-running protocols. Blood lymphocytes isolated before, immediately after, 1h after, and 24h after each exercise test were assessed for markers of apoptosis (Annexin-V(+), HSP60(+)), and CD55, CD59, and CD95 expression by flow cytometry. Lymphocytopenia occurred 1h after intensive and downhill running exercise, but no changes in the percentage of Annexin-V + or HSP60 + lymphocytes were found. Numbers of CD95(+), CD55(dim), and CD59(dim) lymphocytes increased immediately after intensive and downhill exercise, which were attributed to the selective mobilization and subsequent efflux of CD8(+) and CD56(+) lymphocyte subsets. No differences were found between the intensive and downhill protocols. In conclusion, apoptosis of circulating lymphocytes does not appear to contribute to exercise-induced lymphocytopenia.

Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies.

OBJECTIVE: To evaluate the risk of chronic traumatic brain injury from amateur boxing. SETTING: Secondary research performed by combination of sport physicians and clinical academics. DESIGN, DATA SOURCES, AND METHODS: Systematic review of observational studies in which chronic traumatic brain injury was defined as any abnormality on clinical neurological examination, psychometric testing, neuroimaging studies, and electroencephalography. Studies were identified through database (1950 to date) and bibliographic searches without language restrictions. Two reviewers extracted study characteristics, quality, and data, with adherence to a protocol developed from a widely recommended method for systematic review of observational studies (MOOSE). RESULTS: 36 papers had relevant extractable data (from a detailed evaluation of 93 studies of 943 identified from the initial search). Quality of evidence was generally poor. The best quality studies were those with a cohort design and those that used psychometric tests. These yielded the most negative results: only four of 17 (24%) better quality studies found any indication of chronic traumatic brain injury in a minority of boxers studied. CONCLUSION: There is no strong evidence to associate chronic traumatic brain injury with amateur boxing.

High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects.

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 +/- 9 yr; maximal O2 uptake 62 +/- 6 ml x kg(-1) x min(-1)) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise (P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population (P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.

The effects of marathon running on expression of the complement regulatory proteins CD55 (DAF) and CD59 (MACIF) on red blood cells.

Exercise is known to result in the haemolysis of red blood cells (RBCs). Although mechanical stressors such as footstrike and an increased velocity of blood flow may be involved, the biological mechanisms that underpin RBC haemolysis remain elusive. RBCs are potentially susceptible to lysis by autologous complement activation. RBCs are protected from the lytic effects of complement by regulatory proteins (CRPs) bound to the cell membrane via glycosylphosphatidylinositol (GPI) anchors. This study aimed to determine if marathon running would result in RBC haemolysis through a loss of membrane expression of the CRPs CD55 (decay accelerating factor) and CD59 (membrane attack complex inhibitory factor). Blood samples were obtained from 14 male runners before, within 30 min after, and 24 h after completion of the 2004 London Marathon. RBCs were assessed for cell surface CD55 and CD59 expression using indirect immunofluorescence assays and flow cytometry. No significant changes in the total RBC count, haematocrit or haemoglobin concentrations were found in response to running the marathon (P > 0.05). Blood bilirubin concentrations after the marathon were significantly greater than the pre-race values (P < 0.01). The relative fluorescent intensity (arbitrary units) of CD55 and CD59 expression on RBC membranes did not change in response to the marathon race (P > 0.05). In conclusion, marathon running did not alter the expression of CD55 or CD59 on RBCs, despite concomitant elevations in blood bilirubin concentrations. Consequently, any haemolysis of RBCs that occurred in response to the marathon was not likely due to a loss of membrane bound CRPs and subsequent cell lysis by autologous complement.

The effects of intensive, moderate and downhill treadmill running on human blood lymphocytes expressing the adhesion/activation molecules CD54 (ICAM-1), CD18 (beta2 integrin) and CD53.

This study examined the effects of intensive, moderate and downhill treadmill running on blood lymphocyte expression of adhesion/activation (AA) molecules. Trained subjects completed three treadmill-running protocols of identical duration: (1) an intensive protocol at 80% VO2max to volitional exhaustion, (2) a moderate protocol at 60% VO2max and (3) a -10% downhill (eccentric) protocol at 80% VO2max. Blood samples were taken before, immediately after, 1 and 24 h after exercise. Isolated lymphocytes were assessed for expression of the AA molecules CD54, CD18 and CD53 by flow cytometry. Lymphocyte counts increased immediately after all running protocols. Lymphocytopenia was observed 1 h after the intensive and eccentric protocols only. Plasma creatine kinase increased 24 h after the downhill protocol only. Increases in the number and percentage of CD54+, CD18bright and CD53bright lymphocytes were observed immediately after the intensive and eccentric protocols, with the numbers falling below pre-exercise values at 1 h post-exercise for all protocols. No differences were found between the intensive protocol and the eccentric protocol at the same relative intensity. Analysis of lymphocyte subsets showed that the total number of CD3+, CD4+, CD8+ and CD56+ lymphocytes increased after the intensive protocol before falling below pre-exercise values at 1 h post-exercise. A relatively greater mobilisation of CD56+ and CD8+ cells accounts for the changes in CD54+, CD18bright and CD53bright cell populations. Lymphocytes that enter and exit the circulation following exercise express high levels of AA molecules, which may mediate extravasation and post-exercise lymphocytopenia. This effect appears to be influenced by exercise intensity and not muscle damage.

Immune alterations, lipid peroxidation, and muscle damage following a hill race.

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; alpha-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p < 0.05). TEAC and the cytokine IL-8 increased immediately after the race (p < 0.05). Plasma TNF-alpha remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-alpha response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components.