Short-term, equipment-free high intensity interval training elicits significant improvements in the cardiorespiratory fitness of young adults irrespective of supervision

Introduction:Serious health implications from having low levels of cardiorespiratory fitness (CRF) and/or being overweight in young adulthood are carried forward into later life. High-intensity interval training (HIIT) is a time-effective, potent stimulus for improving CRF and indices of cardiometabolic health. To date, few studies have investigated the use of equipment-free HIIT or the impact of supervision for improving CRF via HIIT.Methods:Thirty healthy young adults (18-30 y) were randomised to 4 weeks equipment-free supervised HIIT (L-HIIT), unsupervised HIIT (H-HIIT) or no-intervention (CON). Measurements of CRF (anaerobic threshold (AT) and VO2peak (VO2)), blood pressure (BP), body mass index (BMI), blood glucose, plasma insulin and muscle architecture were performed at baseline and after the intervention.Results:Both HIIT protocols improved CRF (AT: L-HIIT mean difference (MD) +2.1 (95% CI: 0.34 to 4.03) ml/kg/min; p=0.02; H-HIIT MD +3.01 (1.17 to 4.85) ml/kg/min; p=0.002), VO2: L-HIIT MD +2.94 (0.64 to 5.25) ml/kg/min; p=0.01; H-HIIT MD +2.55 (0.34 to 4.76) ml/kg/min; p=0.03), BMI (L-HIIT MD 0.18 (-0.35 to 0.5) kg/m2; p=0.04; H-HIIT: MD 0.19 (-0.25 to 0.63) kg/m2; p=0.03) and m. vastus lateralis pennation angle (L-HIIT MD 0.2 (0.13 to 0.27)º; p[less than]0.001; H-HIIT MD 0.17 (0.09 to 0.24)º; p[less than]0.001). There was no significant change in BP, glucose or insulin in any of the groups.Conclusions:Four weeks’ time-efficient, equipment-free, bodyweight-based HIIT ais able to elicit improvements in CRF irrespective of supervision status. Unsupervised HIIT may be a useful tool for counteracting the rise of sedentary behaviours and consequent cardiometabolic disorders in young adults

Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans

Background: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men. Methods: Non-hypogonadal men (n=16; 18–30years) were randomized in a double-blinded fashion to receive placebo (P, saline n=8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6mg, n=8], injections, before 6weeks of supervised whole-body RET. Participants underwent dual-energy X-ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses. Results: Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4±2.8 to 55.8±3.1kg, P=0.61 vs. P: 55.9±1.7 to 57.4±1.7kg, P=0.006, effect size (ES)=0.31], composite strength (Z: 40±2.3% vs. P: 49.8±3.3%, P=0.03, ES=1.4), and muscle thickness (Z: 2.7±0.4 to 2.69±0.36cm, P>0.99 vs. P: 2.74±0.32 to 2.91±0.32cm, P0.99 vs. P: 1.9 fold, P0.99 vs. P: 4.7 fold, P=0.0005, ES=0.68; myogenin: Z: 1.3 fold, P>0.99 vs. P: 2.7 fold, P=0.002, ES=0.72), RNA/DNA (Z: 0.47±0.03 to 0.53±0.03, P=0.31 vs. P: 0.50±0.01 to 0.64±0.04, P=0.003, ES=0.72), and RNA/ASP (Z: 5.8±0.4 to 6.8±0.5, P>0.99 vs. P: 6.5±0.2 to 8.9±1.1, P=0.008, ES=0.63) ratios, as well as acute RET-induced phosphorylation of growth signalling proteins (e.g. AKTser473: Z: 2.74±0.6, P=0.2 vs. P: 5.5±1.1 fold change, P0.99 vs. P: 3.6±1 fold change, P=0.002, ES=0.53). Both MPS (Z: 1.45±0.11 to 1.50±0.06%·day−1, P=0.99 vs. P: 1.5±0.12 to 2.0±0.15%·day−1, P=0.01, ES=0.97) and (extrapolated) muscle protein breakdown (Z: 93.16±7.8 vs. P: 129.1±13.8g·day−1, P=0.04, ES=0.92) were reduced with hypogonadism result in lower net protein turnover (3.9±1.1 vs. 1.2±1.1g·day−1, P=0.04, ES=0.95). Conclusions: We conclude that endogenous T sufficiency has a central role in the up-regulation of molecular transducers of RET-induced muscle hypertrophy in humans that cannot be overcome by muscle mechano-transduction alone

Fasting and surgery timing (FaST) audit

Background & aimsInternational guidance advocates the avoidance of prolonged preoperative fasting due to its negative impact on perioperative hydration. This study aimed to assess the adherence to these guidelines for fasting in patients undergoing elective and emergency surgery in the East Midlands region of the UK.MethodsThis prospective audit was performed over a two-month period at five National Health Service (NHS) Trusts across the East Midlands region of the UK. Demographic data, admission and operative details, and length of preoperative fasting were collected on adult patients listed for emergency and elective surgery.ResultsOf the 343 surgical patients included within the study, 50% (n = 172) were male, 78% (n = 266) had elective surgery and 22% (n = 77) underwent emergency surgery. Overall median fasting times (Q1, Q3) were 16.1 (13.0, 19.4) hours for food and 5.8 (3.5, 10.7) hours for clear fluids. Prolonged fasting >12 h was documented in 73% (n = 250) for food, and 21% (n = 71) for clear fluids. Median fasting times from clear fluids and food were longer in the those undergoing emergency surgery when compared with those undergoing elective surgery: 13.0 (6.4, 22.6) vs. 4.9 (3.3, 7.8) hours, and 22.0 (14.0, 37.4) vs. 15.6 (12.9, 17.8) hours respectively, p < 0.0001.ConclusionsDespite international consensus on the duration of preoperative fasting, patients continue to fast from clear fluids and food for prolonged lengths of time. Patients admitted for emergency surgery were more likely to fast for longer than those having elective surgery

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Exploring the efficacy of novel environmental stimuli to improve cardiorespiratory fitness and muscle health in older adults

The UK population is increasing, and people are living longer than ever before, which has implications for the whole of society. Increasing rates of comorbidity and ill-health associated with age is, and will continue to have, significant socioeconomic consequences when considering the treatment of chronic disease and comorbidity, and their implications for hospitalisation and social care for the older adult. The benefits of regular exercise for older adults have been extensively studied and are known to protect against and even reverse the effects of comorbidity. However, rates of exercise uptake amongst older but also younger adults are poor, with a worrying shift to more sedentary lifestyles in an increasingly technological age. The ageing population has also resulted in a generation of comorbid older adults for whom exercise is not possible and as such are prone to muscle wasting. In addition, low cardiorespiratory fitness, which results from prolonged inactivity, is also a risk factor for many cardiovascular and cardiometabolic diseases, and even premature mortality. Higher-intensity exercise interventions with reduced time commitment have been shown to dramatically improve cardiorespiratory fitness and cardiometabolic health in a short timeframe and as such may be more effective in maintaining adherence to regular exercise. However, the health benefits of such regimens have not been extensively studied outside of a supervised, laboratory environment or without utilising expensive gym equipment. This thesis will explore the efficacy of a home-based, high intensity exercise regimen for improving indices of cardiorespiratory fitness in older and younger adults. It shall also explore the effects of supervision on achieving these improvements. Finally, for those who cannot exercise due to older age or co-morbidity, the effects of plant-based treatments on improving blood flow to increase muscle nutrient and oxygen delivery will also be explored

Exploring the efficacy of novel environmental stimuli to improve cardiorespiratory fitness and muscle health in older adults

The UK population is increasing, and people are living longer than ever before, which has implications for the whole of society. Increasing rates of comorbidity and ill-health associated with age is, and will continue to have, significant socioeconomic consequences when considering the treatment of chronic disease and comorbidity, and their implications for hospitalisation and social care for the older adult. The benefits of regular exercise for older adults have been extensively studied and are known to protect against and even reverse the effects of comorbidity. However, rates of exercise uptake amongst older but also younger adults are poor, with a worrying shift to more sedentary lifestyles in an increasingly technological age. The ageing population has also resulted in a generation of comorbid older adults for whom exercise is not possible and as such are prone to muscle wasting. In addition, low cardiorespiratory fitness, which results from prolonged inactivity, is also a risk factor for many cardiovascular and cardiometabolic diseases, and even premature mortality. Higher-intensity exercise interventions with reduced time commitment have been shown to dramatically improve cardiorespiratory fitness and cardiometabolic health in a short timeframe and as such may be more effective in maintaining adherence to regular exercise. However, the health benefits of such regimens have not been extensively studied outside of a supervised, laboratory environment or without utilising expensive gym equipment. This thesis will explore the efficacy of a home-based, high intensity exercise regimen for improving indices of cardiorespiratory fitness in older and younger adults. It shall also explore the effects of supervision on achieving these improvements. Finally, for those who cannot exercise due to older age or co-morbidity, the effects of plant-based treatments on improving blood flow to increase muscle nutrient and oxygen delivery will also be explored

Robotic colorectal surgery: previous laparoscopic colorectal experience is not essential

A background in minimally invasive colorectal surgery (MICS) has been thought to be essential prior to robotic-assisted colorectal surgery (RACS). Our aim was to determine whether MICS is essential prior to starting RACS training based on results from our initial experience with RACS. Two surgeons from our centre received robotic training through the European Academy of Robotic Colorectal Surgery (EARCS). One surgeon had no prior formal MICS training. We reviewed the first 30 consecutive robotic colorectal procedures from a prospectively maintained database between November 2014 and January 2016 at our institution. Fourteen patients were male. Median age was 64.5 years (range 36–82) and BMI was 27.5 (range 20–32.5). Twelve procedures (40%) were performed by the non-MICS-trained surgeon: ten high anterior resections (one conversion), one low anterior resection and one abdomino-perineal resection of rectum (APER). The MICS-trained surgeon performed nine high and four low anterior resections, one APER and in addition three right hemicolectomies and one abdominal suture rectopexy. There were no intra-operative complications and two patients required re-operation. Median post-operative stay was five days (range 1–26). There were two 30-day re-admissions. All oncological resections had clear margins and median node harvest was 18 (range 9–39). Our case series demonstrates that a background in MICS is not essential prior to starting RACS training. Not having prior MICS training should not discourage surgeons from considering applying for a robotic training programme. Safe and successful robotic colorectal services can be established after completing a formal structured robotic training programme

Curcumin Enhances Fed-State Muscle Microvascular Perfusion but Not Leg Glucose Uptake in Older Adults

Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cerebral and leg macrovascular blood flow, leg muscle microvascular blood flow, brachial artery endothelial function, and leg insulin and glucose responses in healthy older adults (n = 12, 50% male, 73 &plusmn; 1 year). Curcumin enhanced m. tibialis anterior microvascular blood volume (MBV) at 180 and 240 min following the ONS (baseline: 1.0 vs. 180 min: 1.08 &plusmn; 0.02, p = 0.01 vs. 240 min: 1.08 &plusmn; 0.03, p = 0.01), and MBV was significantly higher compared with the control at both time points (p &lt; 0.05). MBV increased from baseline in the m. vastus lateralis at 240 min after the ONS in both groups (p &lt; 0.05), and there were no significant differences between groups. Following the ONS, leg blood flow and leg vascular conductance increased, and leg vascular resistance decreased similarly in both conditions (p &lt; 0.05). Brachial artery flow-mediated dilation and middle cerebral artery blood flow were unchanged in both conditions (p &gt; 0.05). Similarly, the curcumin and control groups demonstrated comparable increases in glucose uptake and insulin in response to the ONS. Thus, acute curcumin supplementation enhanced ONS-induced increases in m. tibialis anterior MBV without potentiating m. vastus lateralis MBV, muscle glucose uptake, or systemic endothelial or macrovascular function in healthy older adults