Association between pretreatment haemoglobin levels and morphometric characteristics of the tumour, response to neoadjuvant treatment and long-term outcomes in patients with locally advanced rectal cancers

Aim The study was carried out to investigate whether pretreatment haemoglobin (Hb) levels act as a biomar- ker in the management of patients with locally advanced rectal cancer. Method\ud We prospectively collected data on all patients within our cancer network with localized low rectal cancer treated with preoperative radiotherapy/chemora- diotherapy at Mount Vernon Centre for Cancer Treat- ment between March 1994 and July 2008. Pretreatment Hb level was assessed as an independent variable for the whole study sample and dichotomised at a value of 12 g/dl. A multivariate analysis of covariance (MANCOVA) was conducted on parameters that had significant association on univariate analysis of covariance (ANCOVA) and cor- relational (Kendall tau/Pearson) analyses. Kaplan – Meier survival analysis and Cox proportional hazard models were used to determine significant prognostic markers. Statistical significance was set at 0.05. Results 463 patients (male/female 2:1; median age = 66 years, interquartile range = 56.5 – 73.0) were included in the analysis. There was significant tumour response of T stage ( P < 0.001) and N stage ( P < 0.001), with 17.6% of patients achieving a pathological complete response. Pretreatment Hb value was inversely related to the craniocaudal vertical tumour length ( P = 0.02) and pretreatment T stage of the tumour ( P = 0.01). Patients with Hb levels of < 12 g/dl and moderately differenti- ated adenocarcinoma were less responsive. Local recur- rence was more common in patients with a pretreatment Hb of < 12 g/dl (hazard ratio = 1.78) over a median follow up of 24 months, but this was not statistically significant ( P = 0.08). Conclusion The pretreatment Hb level might be used as a biomarker of rectal tumour morphology, response to neoadjuvant chemoradiation and risk of local recur- renc

Supervised exercise training and increased physical activity to reduce cardiovascular disease risk in women with polycystic ovary syndrome: Study protocol for a randomized controlled feasibility trial

Background: Polycystic ovary syndrome (PCOS) affects up to 20% of women and is characterised by higher amounts of visceral fat, obesity, insulin resistance, dyslipidemia and reproductive and cardiometabolic complications. Increased oxidised low-density lipoprotein (LDL) concentrations have been associated with an increased risk of cardiovascular disease (CVD)-related events. Oxidised LDL is rarely used as a marker for CVD risk in PCOS-related studies despite its widely accepted role in atherogenesis and the increased risk factors associated with PCOS. Additionally, prolonged periods of sedentary behaviour can negatively affect metabolic health. No studies have specifically examined the effects of reducing sedentary behaviour on CVD risk in PCOS with a lifestyle physical activity intervention. The aim of the current study is to measure the feasibility of a randomised controlled trial (RCT) examining the effects of supervised exercise and reducing sedentary behaviour in women with PCOS on CVD risk. Methods/design: A feasibility, exploratory RCT will be conducted. Fifty-one pre-menopausal females will be randomly allocated between an exercise group (EG), a lifestyle physical activity group (LPAG) and a control group. Participants in the EG will undertake a 12-week supervised aerobic exercise programme. The LPAG will aim to increase daily physical activity and reduce sedentary behaviour for 12 weeks. The control group will not take part in any intervention. Primary outcomes are feasibility and acceptability of the intervention and procedures. Secondary outcomes are oxidised LDL, aerobic fitness, blood lipid profile, fasting glucose and insulin, testosterone and inflammatory markers. Discussion: PCOS is associated with various increased risk factors for CVD, including hypertension, dyslipidemia, abdominal obesity, insulin resistance, and inflammation. Whether oxidised LDL has a role in this increased risk is not yet known. The present study aims to measure the feasibility of implementing structured exercise training and/or increased lifestyle physical activity in women with PCOS, so that a subsequent adequately powered RCT can be designed. The results from the study will be used to refine the interventions and determine the acceptability of the study design. A limitation is that some self-monitoring in the lifestyle physical activity group may not be reliable or replicable, for example inputting information about time spent cleaning/gardening

Effects of lower limb angioplasty on endothelial-dependent and -independent microvascular reactivity

Background: Percutaneous Transluminal Angioplasty (PTA) of the lower limb improves arterial flow and claudication symptoms, but the effects on cutaneous microvascular perfusion and reactivity have not been previously reported. Report: Cutaneous microvascular function in the feet was assessed in 12 patients with intermittent claudication before and after PTA using Laser Doppler Fluximetry (LDF) with transcutaneous iontophoretic administration of acetylcholine and sodium nitroprusside. Maximum vasodilator responses to both endothelial-dependent and independent vasodilators were increased following PTA. Conclusions: Large vessel intervention to improve macrovascular flow has additional benefits on the downstreamcutaneous microcirculation to improve vasodilator responsiveness. These effects may be clinically important to reduce the risk of ischaemic ulceration and tissue breakdown

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Real-life adaptations in walking patterns in patients with established peripheral arterial disease assessed using a global positioning system in the community: A cohort study

Objective: Lower extremity peripheral arterial disease (PAD) is a chronic condition most commonly presenting with intermittent claudication (IC). IC limits walking ability and may negatively affect health-related quality of life. Treadmill assessment of maximal walking distance (MWD) is the gold standard to assess PAD symptom severity. Despite being a well-established and reproducible tool, it may be inappropriate (due to frailty or fear) for some patients and only describes maximal abilities for a single walk test. Global Positioning Systems (GPS) have been proposed as reliable and reproducible tool to measure total, mean and maximal walking distances in PAD patients, in the community setting. Using GPS our study attempted to explore what happens to the walking ability of patients with IC following no intervention under "real-life" conditions. Design and Methods: Using the GlobalSat DG100 GPS, forty-three patients (69±9yrs; 9 female; no invasive interventions or rehabilitation) undertook two 60-minute walking assessments, 6 months apart. Assessments took place in community spaces that had even terrain, no tall trees or buildings and were free from motorised vehicles. GPS-measured maximum walking distance was the main study outcome measure. Results: Over the 6-month period, patients demonstrated significantly shorter GPS-measured, mean (552m vs 334m; p=0.02) and maximum (714m vs 545m; p=0.04) walking distances, stopping also more frequently (9 v 5 times; p=0.03). Conclusions: Given the reported symptom progression we advocate early intervention (e.g. exercise interventions) combined with frequent patient monitoring in attempts to maintain or improve walking ability. Key Words: peripheral arterial disease; Global Position System; maximum walking distance; intermittent claudication; community assessments

Contrasting Effects of Varicose Vein Surgery on Endothelial-dependent and -independent Cutaneous Vasodilation in the Perimalleolar Region

AbstractObjectivesTo evaluate the effects of varicose vein surgery on cutaneous microvascular perfusion and vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) in the gaiter area of patients with great saphenous vein insufficiency.MethodsTwenty-nine patients with isolated great saphenous vein incompetence attended three study mornings (before surgery, and 6–8 weeks and 6 months after sapheno-femoral ligation+partial stripping) during which cutaneous microvascular responses were measured in the supine and standing positions using laser Doppler fluximetry (LDF) combined with incremental-dose iontophoretic administration of endothelial-dependent (Ach) and -independent (SNP) vasodilators.ResultsVaricose vein surgery had no significant effect on baseline cutaneous perfusion or the microvascular response to Ach: e.g. peak vasodilator responses to the 1000μC stimulus were mean 58 SEM 7, 64 SEM 6 and 65 SEM 7PU on the pre-operative, 6–8 weeks and 6 months assessments. In contrast, the corresponding responses to SNP were significantly increased following surgery: e.g. at 2000μC, mean 63 SEM 9, 142 SEM 4 and 157 SEM 9PU (p<0.0001) in the upright position.ConclusionsSapheno-femoral ligation and partial stripping in patients with great saphenous vein insufficiency improves endothelial-independent cutaneous vasodilator function at the gaiter area, which may at least partly explain the benefits of surgery in reducing the risk of venous ulceration

Dietary nitrate does not modify blood pressure and cardiac output at rest and during exercise in older adults : a randomised cross over study

Dietary nitrate (〖NO〗_3^-) supplementation has been associated with improved vascular and metabolic health. We conducted a double-blind, cross-over, placebo-controlled RCT to investigate the effects of 7-day consumption of beetroot juice compared with placebo on 1) blood pressure (BP) measured in resting conditions and during exercise, 2) cardiac and peripheral vascular function and 3) biomarkers of inflammation, oxidative stress and endothelial integrity. Twenty non-smoking healthy participants aged 60-75y and BMI 20.0-29.9kg/m2 were recruited. Measurement were conducted before and after each 7-day intervention period. Consumption of 〖NO〗_3^- had no effect on resting systolic and diastolic BP. 〖NO〗_3^- consumption did not improve indexes of central and peripheral cardiac function responses during cardiopulmonary exercise testing. Dietary 〖NO〗_3^- supplementation did not modify biomarkers of inflammation, oxidative stress and endothelial integrity. This study do not support the short-term benefits of dietary 〖NO〗_3^- supplementation on physiological and biochemical markers of vascular health in older healthy adults. Trial Registration: ISRCTN1906495

Supervised exercise training as an adjunctive therapy for venous leg ulcers: study protocol for a randomised controlled trial

Background: Venous leg ulcers are common, chronic wounds that are painful and reduce quality of life. Compression therapy is known to assist in the healing of venous leg ulceration. Supervised exercise training that targets an improvement in calf muscle pump function might be a useful adjunctive therapy for enhancing ulcer healing and other aspects of physical and mental health. However, the evidence of exercise for individuals with venous ulcers is sparse. Here, we describe the protocol for a study that aims to assess the feasibility of undertaking a randomised controlled trial of a supervised exercise programme in people who are receiving compression for venous ulceration. Methods/Design: This is a randomised, controlled, assessor-blinded, two-centre, feasibility trial with two parallel groups. Eighty adults who are receiving lower-limb compression for a venous leg ulcer will be randomly assigned to receive usual care (compression only) or usual care plus a 12-week supervised exercise programme. Participants in the exercise group will be invited to undertake three, 60-minute sessions of supervised exercise each week, and each session will involve a combination of treadmill walking, upright cycling and strength and flexibility exercises for the lower limbs. Participants will be assessed before randomisation and 3, 6 and 12 months after randomisation. Primary outcomes include rates of recruitment, retention and adherence. Secondary outcomes include time to ulcer healing, proportion of participants healed, percentage and absolute change in ulcer size, health-related quality of life (EQ-5D-5L and VEINES-QOL/Sym), lower-limb cutaneous microvascular function (laser Doppler flowmetry coupled with iontophoresis) and physical fitness (30-second sit-to-stand test, chair sit and reach test, 6-minute walk test and ankle range of motion). The costs associated with the exercise programme and health-care utilisation will be calculated. We will also complete interviews with a sub-sample of participants to explore their experiences of having a venous ulcer and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to refine the supervised exercise programme, investigate the acceptability of the intervention and study design and determine the most appropriate outcome measures, thereby providing estimates of the factors needed to design an adequately powered trial across several centres

Low-intensity resistance exercise with blood flow restriction for patients with claudication: A randomized controlled feasibility trial

Background: Claudication is a common and debilitating symptom of peripheral artery disease, resulting in poor exercise performance and quality of life (QoL). Supervised exercise programs are an effective rehabilitation for patients with claudication, but they are poorly adhered to, in part due to the high pain and effort associated with walking, aerobic, and resistance exercise. Low-intensity resistance exercise with blood flow restriction (BFR) represents an alternative exercise method for individuals who are intolerant to high-intensity protocols. The aim of this study was to evaluate the feasibility of a supervised BFR program in patients with claudication. Methods: Thirty patients with stable claudication completed an 8-week supervised exercise program and were randomized to either BFR (n = 15) or a control of matched exercise without BFR (control; n = 15). Feasibility, safety, and efficacy were assessed. Results: All success criteria of the feasibility trial were met. Exercise adherence was high (BFR = 78.3%, control = 83.8%), loss to follow up was 10%, and there were no adverse events. Clinical improvement in walking was achieved in 86% of patients in the BFR group but in only 46% of patients in the control group. Time to claudication pain during walking increased by 35% for BFR but was unchanged for the control. QoL for the BFR group showed improved mobility, ability to do usual activities, pain, depression, and overall health at follow up. Conclusion: A supervised blood flow restriction program is feasible in patients with claudication and has the potential to increase exercise performance, reduce pain, and improve QoL. (Clinicaltrials.gov Identifier: NCT04890275

Dietary nitrate does not have an effect on physical activity outcomes in healthy older adults : a randomized, cross-over trial

Dietary nitrate (〖NO〗_3^-) ingestion appears to enhance exercise capacity and performance in young individuals whereas inconclusive findings have been reported in older people. We conducted a double-blind, cross-over randomized clinical trial in older normal weight and overweight healthy participants testing whether beetroot juice (a rich source of 〖NO〗_3^-) for one week may increase nitric oxide bioavailability via the non-enzymatic pathway and enhance 1) exercise capacity during an incremental exercise test, 2) physical capability and 3) free-living physical activity. Twenty non-smoking healthy participants aged 60-75y and BMI 20.0-29.9kg/m2 were included. Pre and post supplementation resting, sub-maximal, maximal and recovery gas exchanges were measured. Physical capability was measured by hand-grip strength (HGS), time-up-and-go (TUG), repeated-chair-rising-test (RCRT), and 10m walking speed (WLS). Free-living physical activity was assessed by triaxal accelerometry. Changes in urinary and plasma 〖NO〗_3^- concentrations were measured by gas chromatography mass spectrometry. Nineteen participants (M/F=9/10) completed the study. Beetroot juice increased significantly both plasma and urinary 〖NO〗_3^- concentrations (p<0.001) compared to placebo. Beetroot juice did not influence resting, sub-maximal and maximal oxygen consumption during the incremental exercise test. In addition, measures of physical capability and physical activity levels measured in free-living conditions were not modified by beetroot juice ingestion. The positive effects of beetroot juice ingestion on exercise performance seen in young individuals were not replicated in healthy, older adults. Whether aging represents a modifier of the effects of dietary 〖NO〗_3^- on muscular performance is not known and mechanistic studies and larger trials are needed to test this hypothesis. Keywords: inorganic nitrate, nitric oxide, exercise, oxygen consumption, agin