Effects of resistance training on quality of life, fatigue, physical function, and muscular strength during chemotherapy treatment: a systematic review and meta-analysis.

PURPOSE: To systematically review and meta-analyse the efficacy of resistance training on quality of life (QOL), fatigue, physical function, and muscular strength in people diagnosed with cancer undergoing chemotherapy. METHODS: Electronic databases PubMed, Cochrane Central, CINAHL, SCOPUS and Web of Science were systematically searched for randomised controlled trials (RCTs) that compared the effects of resistance training to control on QOL, fatigue, physical function, and lower-body and upper-body muscular strength in adults undergoing chemotherapy. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assess using the risk of bias tool for randomised trials (RoB 2). RESULTS: Seven RCTs encompassing 561 participants were included. The pooled results of seven RCTs showed that resistance training during chemotherapy significantly improved lower-body strength (n = 555, SMD 0.33, 95% CI 0.12 to 0.53, moderate-quality evidence, I2 = 23%) compared to control. There was no evidence for an effect of resistance training on QOL (n = 373, SMD 0.13, 95% CI -0.15 to 0.42, low-quality evidence, I2 = 0%), fatigue (n = 373, SMD -0.08, 95% CI -0.37 to 0.22, low-quality evidence, I2 = 20%), physical function (n = 198, SMD 0.61, 95% CI -0.73 to 1.95, very low-quality evidence, I2 = 83%), or upper-body strength (n = 413, SMD 0.37, 95% CI -0.07 to 0.80, very low-quality evidence, I2 = 69%). CONCLUSIONS: Resistance training may improve lower-body strength in patients undergoing chemotherapy treatment compared to control.

The Effect of a Very-Low-Calorie Diet (VLCD) vs. a Moderate Energy Deficit Diet in Obese Women with Polycystic Ovary Syndrome (PCOS)-A Randomised Controlled Trial.

We performed an open-label, randomised controlled trial to compare the effects of a very-low-calorie diet (VLCD) vs. moderate energy deficit approach on body weight, body composition, free androgen index (FAI), and metabolic markers in obese women with polycystic ovary syndrome (PCOS). Forty eligible patients were randomly assigned to a VLCD (n = 21) or a conventional energy deficit approach (n = 19) over the same period. After eight weeks, both groups experienced significant weight loss; however, this was greater in the VLCD arm (-10.9% vs. -3.9%, p < 0.0001). There was also a trend towards a reduction in FAI in the VLCD group compared to the energy deficit group (-32.3% vs. -7.7%, p = 0.07). In the VLCD arm, two women (18%) had a biochemical remission of PCOS (FAI < 4); this was not the case for any of the participants in the energy deficit arm. There was a significant within-group increase in the sex-hormone-binding globulin (p = 0.002) and reductions in fasting blood glucose (p = 0.010) and waist to hip ratio (p = 0.04) in the VLCD arm, but not in the energy deficit arm. The VLCD resulted in significantly greater weight reduction and was accompanied by more pronounced improvements in hyperandrogenaemia, body composition, and several metabolic parameters in obese women with PCOS as compared to the energy deficit approach.

Feasibility of delivering supervised exercise training following surgical resection and during adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PRECISE): a case series.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm, with surgical resection and adjuvant chemotherapy the only curative treatment. Treatment-related toxicities place a considerable burden on patients although exercise training has shown promise is helping to manage such adversities and facilitate rehabilitation. The feasibility and safety of exercise training as a supportive therapy during adjuvant chemotherapy remains unknown. METHODS: Patients with PDAC were screened post-surgical resection and enrolled in a 16-week, progressive, concurrent exercise programme alongside their chemotherapy regimen. Feasibility was the primary objective detailing recruitment, retention and adherence rates throughout as well as the safety and fidelity of the intervention. Secondarily, the impact on functional fitness and patient-reported outcomes was captured at baseline, post-intervention and 3-month follow up. RESULTS: Eight patients consented to participate in this trial, with five proceeding to enrol in exercise training. Concurrent exercise training is feasible and safe during adjuvant chemotherapy and prevented an expected decline in functional fitness and patient-reported outcomes during this time. DISCUSSION: This case series provides preliminary evidence that concurrent exercise training during adjuvant therapy is safe, feasible and well tolerated, preventing an expected decline in functional fitness, muscular strength and health-related quality of life (HRQoL). Given the adverse effects of treatment, these findings are promising and provide further evidence for the inclusion of exercise training as a standard of care for surgical rehabilitation and managing treatment-related toxicities. Future research should explore the impact of exercise training during neoadjuvant chemotherapy, with prehabilitation now standard practice for borderline resectable disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04305067, prospectively registered 12/03/2020, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04305067 .

Feasibility of a novel exercise prehabilitation programme in patients scheduled for elective colorectal surgery: a feasibility randomised controlled trial.

BACKGROUND AND OBJECTIVES: To investigate the feasibility of delivering a functional exercise-based prehabilitation intervention and its effects on postoperative length of hospital stay, preoperative physical functioning and health-related quality of life in elective colorectal surgery. MATERIALS AND METHODS: In this randomised controlled feasibility trial, 22 elective colorectal surgery patients were randomly assigned to exercise prehabilitation (n = 11) or standard care (n = 11). Feasibility of delivering the intervention was assessed based on recruitment and compliance to the intervention. Impact on postoperative length of hospital stay and complications, preoperative physical functioning (timed up and go test, five times sit to stand, stair climb test, handgrip dynamometry and 6-min walk test) and health-related quality of life were also assessed. RESULTS: Over 42% of patients (84/198) screened were deemed ineligible for prehabilitation due to insufficient time existing prior to scheduled surgery. Of those who were eligible, approximately 18% consented to the trial. Median length of hospital stay was 8 [range 6-27] and 10 [range 5-12] days respectively for the standard care and prehabilitation groups. Patterns towards preoperative improvements for the timed up and go test, stair climb test and 6-min walk test were observed for all participants receiving prehabilitation but not standard care. CONCLUSIONS: Despite prehabilitation appearing to convey positive benefits on physical functioning, short surgical wait times and patient engagement represent major obstacles to implementing exercise prehabilitation programmes in colorectal cancer patients.

Impaired heat shock protein 72 expression in women with polycystic ovary syndrome following a supervised exercise programme.

Induction of heat shock protein expression and the heat shock (stress) response are seen in exercise. This exercise-induced response is thought protective against cellular stress through the expression of heat shock proteins. The highly inducible heat shock protein 72 (HSP72) has been shown to be expressed in a number of stress-related conditions, but not investigated in women with polycystic ovary syndrome (PCOS). Twenty-one women (10 controls, 11 with PCOS) concluded an 8-week supervised, moderate-intensity exercise programme. Monocytes and lymphocytes were analysed by flow cytometry for HSP72 expression from blood samples prior to, mid-way and at the completion of the programme. The monocyte HSP72 expression showed an increase from baseline values through mid-way (p = 0.025), and at the completion of the programme (p = 0.011) only in the control group, the PCOS group showed no significant change. This pattern was similar for lymphocyte HSP72 expression where a significant increase was found at the completion of the programme (p = 0.01) only in the control group. The magnitude of increased HSP72 expression following completion of the programme was linked to baseline values only in the control group. In conclusion, increased HSP72 expression to exercise over an 8-week period was seen in control but not in PCOS women, suggesting that there is an impairment of HSP72 expression in response to exercise in these women.

The CD105:CD106 microparticle ratio is CD106 dominant in polycystic ovary syndrome compared to type 2 diabetes and healthy subjects.

BACKGROUND: A retrospective analysis was carried out from patients and controls during the past 5 years from a series of studies investigating endothelial microparticles (MP). METHODS: In total, 319 samples from 207 individuals were included in this analysis, from patients with type 2 diabetes (T2D, n = 105), women with polycystic ovary syndrome (PCOS, n = 145) and healthy volunteers (n = 69). All data were generated via the same flow cytometry protocol with the same antibody clones. Endothelial markers CD105 (Endoglin) and CD106 (Vascular cell adhesion molecule-1) were used to enumerate MP in venous blood. RESULTS: The ratio of CD105MP:CD106MP was significantly different between groups (F = 63.43, p < 0.0001). Women with PCOS were found to have a median CD105MP:CD106MP ratio of 0.40 (IQR 0.24-0.57), suggesting approximately two CD106MP were found per CD105MP. The T2D group showed a median ratio of 2.32 (1.51-3.69) whereas in healthy volunteers the ratio was 2.21 (1.63-3.55). Serum intercellular adhesion molecule-1 was also shown to be significantly increased in PCOS when compared with control or T2D groups (F = 14.5, p < 0.001). CONCLUSION: These data suggest that women with PCOS have an altered endothelial MP release in favour of CD106. Thus a potential activated endothelial state exists in women with PCOS with a shift towards a predominantly CD106MP profile.

Exercise prehabilitation in elective intra-cavity surgery: A role within the ERAS pathway? A narrative review.

The Enhanced Recovery after Surgery (ERAS) model integrates several elements of perioperative care into a standardised clinical pathway for surgical patients. ERAS programmes aim to reduce the rate of complications, improve surgical recovery, and limit postoperative length of hospital stay (LOHS). One area of growing interest that is not currently included within ERAS protocols is the use of exercise prehabilitation (PREHAB) interventions. PREHAB refers to the systematic process of improving functional capacity of the patient to withstand the upcoming physiological stress of surgery. A number of recent systematic reviews have examined the role of PREHAB prior to elective intra-cavity surgery. However, the results have been conflicting and a definitive conclusion has not been obtained. Furthermore, a summary of the research area focussing exclusively on the therapeutic potential of exercise prior to intra-cavity surgery is yet to be undertaken. Clarification is required to better inform perioperative care and advance the research field. Therefore, this "review of reviews" provides a critical overview of currently available evidence on the effect of exercise PREHAB in patients undergoing i) coronary artery bypass graft surgery (CABG), ii) lung resection surgery, and iii) gastrointestinal and colorectal surgery. We discuss the findings of systematic reviews and meta-analyses and supplement these with recently published clinical trials. This article summarises the research findings and identifies pertinent gaps in the research area that warrant further investigation. Finally, studies are conceptually synthesised to discuss the feasibility of PREHAB in clinical practice and its potential role within the ERAS pathway.

The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight. METHODS: Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month - baseline) ± standard deviation. RESULTS: Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls -0.17 ± 0.26 but not PCOS -0.12 ± 0.28; between groups difference, 95% confidence interval = -0.14 - 0.26, P = 0.41. No significant changes were noted in cIMT or RHI. CONCLUSIONS: Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3-4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity and suggest a potential beneficial effect on platelet function and atherothrombotic risk at 6 months of treatment. TRIAL REGISTRATION: Clinical trial reg. no. ISRCTN48560305. Date of registration 22/05/2012.

A comparison of cardiovascular risk indices in patients with polycystic ovary syndrome with and without coexisting nonalcoholic fatty liver disease.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have an adverse cardiovascular risk profile and an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which is also associated with an adverse cardiovascular risk profile. OBJECTIVE: To compare the cardiovascular risk profile of women with PCOS alone and women with PCOS and NAFLD. DESIGN, SETTING AND PARTICIPANTS: Twenty-five oligoanovulatory women with PCOS were screened for NAFLD (including liver biopsy if appropriate) and had their cardiovascular risk factors measured which included the inflammatory marker C-reactive protein (CRP), endothelial function {measured using endoPAT 2000 and serum markers [intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin]}, clot structure and function [maximum absorbance (MA) and lysis potential (LT)]. RESULTS: Twelve patients had confirmed PCOS without evidence of NAFLD, and 13 patients had confirmed PCOS with evidence of NAFLD. The PCOS and NAFLD group were heavier (BMI 43·9 ± 2·2 kg/m(2) ) compared with the PCOS alone group (BMI 37·6 ± 1·4 kg/m(2) P = 0·03). There was no difference in CRP (7·57 ± 0·95 vs 6·59 ± 1·87 mm P = 0·62) or endothelial function (RH-PAT 1·96 ± 0·1 vs 1·74 ± 0·16 P = 0·25), ICAM-1 (221 ± 48 vs 250 ± 60 ng/ml P = 0·19), VCAM-1 (2124 ± 78 vs 2314 ± 91 ng/ml P = 0·13), E-selectin (33·9 ± 3·3 vs 39·5 ± 15·5 ng/ml P = 0·31) and P-selectin (101·0 ± 6·6 vs 95·9 ± 10·2 ng/ml P = 0·69). There was no difference in clot formation or lysis. CONCLUSION: The patients with PCOS and NAFLD were heavier compared with patients with PCOS alone. Despite this, we were unable to demonstrate differences in inflammatory markers, endothelial function or clot structure and function, suggesting that severity of steatosis is not the most important determinant of cardiovascular risk in PCOS.

Increased inducible heat shock protein 72 expression associated with PBMC isolated from patients with haematological tumours.

BACKGROUND: Heat shock protein 72 (Hsp72) is a highly inducible stress protein and molecular chaperone. Cancers have been shown to be associated with increased Hsp72 expression within the tumour itself and this may lead to resistance to apoptosis. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from patients diagnosed with chronic lymphocytic leukaemia (CLL) (n = 27) and chronic myelomonocytic leukaemia (CMML) (n = 16) and Hsp72 expression was characterized on both the cell surface and intracellularly by flow cytometry. To allow for comparison PBMC from breast cancer patients (n = 25) and healthy volunteers (n = 19) were included. RESULTS: Both lymphocytes and monocytes from CLL and CMML patients showed high levels of total Hsp72 expression (4-6 fold increase) in comparison to breast cancer and healthy subjects. The majority of Hsp72 in these tumours was determined to be cell-surface expressed (64-93% of cell total Hsp72). CONCLUSIONS: A correlation was observed between lymphocyte and monocyte total Hsp72 expression (p < 0.001) suggesting a common stress response pathway may exist in these blood cells and there are stress conditions present within the circulation. Hsp72 expression was not found to be related to white blood cell count.

Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress.

While in vitro work has revealed that dehydration and hyperthermia can elicit increased cellular and oxidative stress, in vivo research linking dehydration, hyperthermia, and oxidative stress is limited. The purpose of this study was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male, trained cyclists (power output (W) at lactate threshold (LT): 199 ± 19 W) completed 90 min of cycling exercise at 95% LT followed by a 5-km time trial (TT) in 4 trials: (i) euhydration in a warm environment (EU-W, control), (ii) dehydration in a warm environment (DE-W), (iii) euhydration in a thermoneutral environment (EU-T), and (iv) dehydration in a thermoneutral environment (DE-T) (W: 33.9 ± 0.9 °C; T: 23.0 ± 1.0 °C). Oxidized glutathione (GSSG) increased significantly postexercise in dehydration trials only (DE-W: p < 0.01, DE-T: p = 0.03), and while not significant, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) tended to increase postexercise in dehydration trials (p = 0.08 for both). Monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, we found evidence of increased cellular stress (measured via HSP) during all trials independent of hydration status and environment. Finally, both 90-min and 5-km TT performances were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia, and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat.

Identification of methicillin-resistant Staphylococcus aureus-specific peptides for targeted photoantimicrobial chemotherapy.

The increasing prevalence of multi-drug resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), necessitates development of alternative modes of bacterial targeting which are not hindered by antibiotic resistance and minimise collateral damage. To achieve this, the FliTrx™ bacterially-displayed peptide library was panned against MRSA and randomly selected clones (n = 20) were DNA sequenced. One selected peptide was synthesised as both cyclic and linear constructs. Binding of the cyclic construct was observed by flow cytometry against isolates of MRSA whilst the linear construct showed low affinity. Low reactivity was observed with other Staphylococcal sp., gram-negative bacteria and human keratinocytes. The selected peptide was also cloned in-frame, within the thioredoxin gene into the pPROTet.E 6xHN vector for protein expression. A porphyrin photosensitiser (5-(4-isothiocyanatophenyl)-10,15,20-tris(4-N-methylpyridiniumyl)porphyrin trichloride) was conjugated to the recombinant protein and the in vitro cytotoxic effect of the resulting bioconjugate was determined against MRSA and other non-specific bacterial and mammalian cell lines. Photoantimicrobial chemotherapy (PACT) using the bioconjugate showed a 66% reduction in MRSA growth in comparison with non-irradiated cells. This work demonstrates the potential to isolate peptides with binding specificity against MRSA that can be used for targeted PACT, providing an effective alternative to antibody targeting.

Endothelial function and stress response after simulated dives to 18 msw breathing air or oxygen.

INTRODUCTION: Decompression sickness is caused by gas bubbles released upon decompression. These bubbles have the potential to occlude blood vessels and damage the vascular endothelium. The aim of this study was to quantify damage to the vascular endothelium resulting from decompression by measuring endothelial microparticles (MP) and endothelial function. METHODS: Five healthy male volunteers undertook a simulated (hyperbaric chamber) air dive and 1 wk later a second dive breathing 100% oxygen at 283 kPa (18 msw) for 60 min bottom time, decompressed with 5-min stops at 161 kPa (6 msw) and 131 kPa (3 msw). Endothelial function was tested pre- and postdive by reactive hyperemia peripheral artery tonometry (RH-PAT) and CD105 (Endoglin) positive MP were quantified by flow cytometry. Plasma E- and P-selectin, interleukin-6, and serum cortisol were also quantified. RESULTS: RH-PAT showed a significantly decreased endothelial function post-decompression after breathing air when compared to oxygen (-0.33 +/- 0.27 vs. +0.18 +/- 0.14). CD105 MP pre- and postdive showed no change on the oxygen dive (460 +/- 370 to 360 +/- 163), however, they increased after breathing air (440 +/- 70 to 1306 +/- 359). There was no change in expression of CD105 on MP. Furthermore no changes were observed in plasma E- or P-selectin, IL-6, or serum cortisol. CONCLUSION: From the data, at least in the time frame involved, there appears to be no detectable physiological/stress response to decompression, rather decompression from breathing air probably caused mechanical damage to the endothelium, resulting in both MP release and a reduction in endothelial function.