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This review aims to provide clinicians that work in the surgical realm with relevant exercise principles and related research as they consider incorporating prehabilitation into care plans. Exercise is a core component of preoperative health optimization strategies referred to as prehabilitation. The exercise component of prehabilitation aims to improve systemic and loco-regional fitness to increase surgical tolerance and facilitate recovery. Studies demonstrate that greater presurgical physical fitness is associated with improved postsurgical treatment complication rates, recovery, and quality of life. The safety and effectiveness of an exercise prescription requires individualization to the patient’s medical history, exercise preferences, and functional goals within the context of their imminent treatments. However, research has shown that many health professionals express apprehension or discomfort in providing exercise guidance in clinical settings. As interest in the integration of prehabilitation into clinical care grows, an understanding of how to appropriately prescribe exercise within a pre-treatment setting is required.

OBJECTIVE The objective is to characterize the presence of malnutrition, examine the association between malnutrition and baseline functional capacity (FC), and the extent to which patients benefit from preoperative multimodal prehabilitation in patients undergoing lung resection for cancer. METHODS Data from 162 participants enrolled in multimodal prehabilitation or control before lung cancer surgery were analyzed. Malnutrition was measured using the Patient-Generated Subjective Global Assessment (PG-SGA) according to triage levels: low-nutrition-risk (PG-SGA 0-3), moderate-nutrition-risk (4-8) and high-nutrition-risk (≥9). Baseline differences in FC, measured by the 6-minute walk test (6MWT), were compared. Factorial analysis of covariance (ANCOVA) was conducted to examine the effect of nutrition status and intervention on mean change in 6MWT preoperatively. RESULTS 51.2% patients were considered low-nutrition-risk, 37.7% moderate-nutrition-risk, and 11.1% high-nutrition-risk. Low-nutrition-risk patients had significantly higher 6MWT at baseline (mean of 484 m [standard deviation (SD) = 88]) compared with moderate-nutrition-risk (432 m [SD = 107], P = .005) and high-nutrition-risk groups (416 m [SD = 90], P = .022). The adjusted mean change in 6MWT between prehabilitation vs control was 18.1 (95% confidence interval, 3.8 to 32.3) vs 5.6 m (-14.1 to 25.4) in low-nutrition-risk (P = .309), 28.5 (11 to 46) vs -4 m (-31.3 to 23.4) in moderate-nutrition-risk (P = .053), and 58.9 (16.7 to 101.2) vs -39.7 m (-80.2 to 0.826) in high-nutrition-risk group (P = .001). CONCLUSIONS Lung cancer patients at high-nutrition-risk awaiting surgery had significantly lower baseline FC compared with low-nutrition-risk patients but experienced significant improvements in preoperative FC upon receiving multimodal prehabilitation.

To determine the effect of preoperative nutrition and multimodal prehabilitation on clinical and functional outcomes in surgical lung cancer patients. We searched MEDLINE, Cochrane Library and CENTRAL, EMBASE, Scopus, and clinical trial registries ( clinicaltrials.gov , International Clinical Trials Registry Platform and Google Scholar) to identify studies involving a preoperative nutrition-based intervention or multimodal prehabilitation (nutrition with exercise) of at least 7 days, in lung cancer patients awaiting surgery. Studies must have reported results on at least one of the following outcomes: functional capacity, pulmonary function, postoperative complications, and length of hospital stay. The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials. Five studies were included (1 nutrition-only and 4 multimodal prehabilitation studies). Due to substantial heterogeneity in the interventions across studies, a meta-analysis was not conducted. Findings suggest that multimodal prehabilitation, compared with standard hospital care, is associated with improvements in both functional walking capacity and pulmonary function during the preoperative period; however it does not appear to have an effect on postoperative outcomes. Rather, the finding of significantly lower rates of postoperative complications in the intervention group was unique to the nutrition-only study. Multimodal prehabilitation programs that combine nutrition and exercise may have beneficial effects on various physical function outcomes in patients with lung cancer awaiting surgery. Optimizing preoperative nutrition may have postoperative benefits which remain to be confirmed.

BACKGROUND Multimodal prehabilitation, including exercise training, nutritional therapy and anxiety reduction, has been shown to attenuate functional decline associated with surgery. Due to the growing interest in functional status as a targeted surgical outcome, a better understanding of the optimal prescription of exercise is critical. OBJECTIVE The objective is to compare peri-operative functional trajectory in response to two different exercise training protocols within a 4-week, supervised, multimodal prehabilitation programme. DESIGN This was a single blinded, single centre, randomised controlled study. Participants performed four assessments: at baseline, after prehabilitation (just before surgery), and at 1 and 2 months after surgery. PATIENTS Adult patients scheduled for elective resection of nonmetastatic colorectal cancer were included provided there were no absolute contraindications to exercise nor poor language comprehension. INTERVENTION Patients followed either high-intensity interval training (HIIT), or moderate intensity continuous training (MICT), as part of a 4-week multimodal prehabilitation programme. Both groups followed the same supervised resistance training, nutritional therapy and anxiety reduction interventions. All patients followed standardised peri-operative management. MAIN OUTCOME MEASURE Changes in oxygen consumption at anaerobic threshold, measured with sequential cardio-pulmonary exercise testing, were assessed and compared between groups. RESULTS Forty two patients were included in the primary analysis (HIIT n = 21 vs. MICT n = 21), with mean ± SD age 64.5 ± 11.2 years and 62% were men. At 2 months after surgery, 13/21 (62%) in HIIT and 11/21 (52%) in MICT attended the study visits. Both protocols significantly enhanced pre-operative functional capacity, with no difference between groups: mean (95% confidence interval) oxygen consumption at anaerobic threshold 1.97 (0.75 to 3.19) ml kg min in HIIT vs. 1.71 (0.56 to 2.85) in MICT, P = 0.753. At 2 months after surgery, the HIIT group showed a higher improvement in physical fitness: 2.36 (0.378 to 4.34) ml kg min, P = 0.021. No adverse events occurred during the intervention. CONCLUSION Both MICT and HIIT enhanced pre-operative functional capacity. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03361150.

Frailty is a state of vulnerability as a result of decreased reserves. Prehabilitation may increase reserve and improve postoperative outcomes. Our objective was to determine if home-based prehabilitation improves postoperative functional recovery in older adults with frailty having cancer surgery.This double blind randomised trial enrolled people ≥60 yr having elective cancer surgery and ≥3 weeks from enrolment to surgery as eligible. Participation in a remotely supported, home-based exercise prehabilitation program plus nutritional guidance was compared with standard care plus written advice on age-appropriate activity and nutrition. The primary outcome was 6-min walk test (6MWT) distance at the first postoperative clinic visit. Secondary outcomes included physical performance, quality of life, disability, length of stay, non-home discharge, and 30-day readmission.Of 543 patients assessed, 254 were eligible and 204 (80%) were randomised (102 per arm); 182 (94 intervention and 88 control) had surgery and were analysed. Mean age was 74 yr and 57% were female. Mean duration of participation was 5 weeks, mean adherence was 61% (range 0%-100%). We found no significant difference in 6MWT at follow-up (+14 m, 95% confidence interval -26-55 m, P=0.486), or for secondary outcomes. Analyses using a prespecified adherence definition of ≥80% supported improvements in 6MWT distance, complication count, and disability.A home-based prehabilitation program did not significantly improve postoperative recovery or other outcomes in older adults with frailty having cancer surgery. Program adherence may be a key mediator of prehabilitation efficacy.NCT02934230.

The certainty that prehabilitation improves postoperative outcomes is not clear. The objective of this umbrella review (i.e. systematic review of systematic reviews) was to synthesise and evaluate evidence for prehabilitation in improving health, experience, or cost outcomes.We performed an umbrella review of prehabilitation systematic reviews. MEDLINE, Embase, Cochrane, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Joanna Briggs Institute's database, and Web of Science were searched (inception to October 20, 2020). We included all systematic reviews of elective, adult patients undergoing surgery and exposed to a prehabilitation intervention, where health, experience, or cost outcomes were reported. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. Primary syntheses of any prehabilitation were stratified by surgery type.From 1412 titles, 55 systematic reviews were included. For patients with cancer undergoing surgery who participate in any prehabilitation, moderate certainty evidence supports improvements in functional recovery. Low to very low certainty evidence supports reductions in complications (mixed, cardiovascular, and cancer surgery), non-home discharge (orthopaedic surgery), and length of stay (mixed, cardiovascular, and cancer surgery). There was low to very low certainty evidence that exercise prehabilitation reduces the risk of complications, non-home discharge, and length of stay. There was low to very low certainty evidence that nutritional prehabilitation reduces risk of complications, mortality, and length of stay.Low certainty evidence suggests that prehabilitation may improve postoperative outcomes. Future low risk of bias, randomised trials, synthesised using recommended standards, are required to inform practice. Optimal patient selection, intervention design, and intervention duration must also be determined.

Background The enhancement of post-operative care is under constant evolution and, with the addition of enhanced recovery programs, is changing the traditional in-hospital paradigm. Despite these advances, there is a clear lack of focus regarding early post-surgical mobilization, which has been identified as an important aspect of recovery. This pilot study investigates the feasibility of initiating resistance exercise to promote early mobilization in colorectal cancer patients during the in-hospital period. Method Patients participated in a supervised progressive resistance exercise program, adapted to their physical ability (either in bed, seated or standing), within the first 24 h following surgery. They were seen each day during the hospital stay and encouraged to continue exercising upon discharge. All patients were asked to return to the lab at four weeks after surgery for re-evaluation to establish recovery. Results Patient compliance to the in-hospital program was high, with 90% of patients engaging in exercise on the first post-operative day (POD 1) and no adverse effects reported during study. By POD 2, over 70% of patients met enhanced recovery after surgery (ERAS) recommendations. Conclusion It is feasible to initiate a progressive post-operative resistance exercise program in patients undergoing colorectal resection. The results suggest the positive aspects of incorporating resistance exercise into post-operative care. This may facilitate a clear and easy to implement exercise intervention that can take into consideration patient physical status and limited facility space in the hospital environment.

Objective To investigate, in lung cancer patients awaiting elective surgery, the feasibility of delivering a novel four-week multimodal prehabilitation intervention and its effects on preoperative functional capacity and health-related quality of life (HRQoL), compared to standard hospital care. Methods Adult patients awaiting elective thoracotomy for lung cancer stages I, II or IIIa, were approached to participate in an open-label, randomized controlled trial of two parallel arms: multimodal prehabilitation combining a mixed-nutrient supplement with structured supervised and home-based exercise training, and relaxation-strategies (Prehab) or standard hospital care (Control). Feasibility was assessed based on recruitment and adherence rates to the intervention and study outcome assessment. Functional capacity, measured by the 6-min walk test (6MWT), and HRQoL were measured at baseline and after four weeks (preoperative). Results Within 5 months, 34 patients were enrolled and randomized (2:1) to Prehab (n = 24; median age = 67 years) or Control (n = 10; median age = 69 years); recruitment rate of 58.6%. The study was interrupted by the COVID-19 pandemic. Adherence to the prescribed intensity of the supervised exercise program was 84.1% (SD 23.1). Self-reported adherence to the home-based exercise program was 88.2% (SD 21) and to the nutritional supplement, 93.2% (SD 14.2). Adherence to patients’ preoperative assessment was 82% and 88% in Prehab and Control, respectively. The mean adjusted difference in 4-week preoperative 6MWT between groups was 37.7 m (95% CI, −6.1 to 81.4), p = 0.089. There were no differences in HRQoL between groups. Conclusion Within a preoperative timeframe, it was feasible to deliver this novel multimodal prehabilitation intervention in lung cancer patients awaiting surgery.

To determine the effect of preoperative nutrition and multimodal prehabilitation on clinical and functional outcomes in surgical lung cancer patients.We searched MEDLINE, Cochrane Library and CENTRAL, EMBASE, Scopus, and clinical trial registries ( clinicaltrials.gov , International Clinical Trials Registry Platform and Google Scholar) to identify studies involving a preoperative nutrition-based intervention or multimodal prehabilitation (nutrition with exercise) of at least 7 days, in lung cancer patients awaiting surgery. Studies must have reported results on at least one of the following outcomes: functional capacity, pulmonary function, postoperative complications, and length of hospital stay. The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials.Five studies were included (1 nutrition-only and 4 multimodal prehabilitation studies). Due to substantial heterogeneity in the interventions across studies, a meta-analysis was not conducted. Findings suggest that multimodal prehabilitation, compared with standard hospital care, is associated with improvements in both functional walking capacity and pulmonary function during the preoperative period; however it does not appear to have an effect on postoperative outcomes. Rather, the finding of significantly lower rates of postoperative complications in the intervention group was unique to the nutrition-only study.Multimodal prehabilitation programs that combine nutrition and exercise may have beneficial effects on various physical function outcomes in patients with lung cancer awaiting surgery. Optimizing preoperative nutrition may have postoperative benefits which remain to be confirmed.

Just as there is growing interest in enhancing recovery after surgery, prehabilitation is becoming a recognised means of preparing the patient physically for their operation and/or subsequent treatment. Exercise training is an important stimulus for improving low cardiovascular fitness and preserving lean muscle mass, which are critical factors in how well the patient recovers from surgery. Despite the usual focus on exercise, it is important to recognise the contribution of nutritional optimisation and psychological wellbeing for both the adherence and the response to the physical training stimulus. This article reviews the importance of a multi-modal approach to prehabilitation in order to maximise its impact in the pre-surgical period, as well as critical future steps in its development and integration in the healthcare system.

Purpose Multimodal prehabilitation programs (exercise, nutrition, and anxiety reduction) have been shown to be successful for enhancing patients' physical function prior to surgery, although adherence remains a challenge. Given the short pre-operative period, maintaining adherence is critical to maximize program effectiveness. This study was designed to better understand patients' perspectives of prehabilitation and to identify factors related to program adherence.Methods A qualitative descriptive study was conducted based on 52 cancer patients enrolled in a prehabilitation program at the Montreal General Hospital, Montreal, Canada. Data was collected with a structured questionnaire designed to evaluate the program.Results Patients enjoyed their experience in prehabilitation, especially the exercise program and training sessions. The primary motivating factor for participation was to be physically prepared for the surgery. The most challenging exercise component was resistance training, while the most enjoyed was the aerobic training. Approximately 50% of patients were interested in group fitness classes as opposed to supervised individual training sessions for reasons related to social support. The preferred methods for exercise program delivery were home-based and one supervised exercise session per week. The biggest barrier to participation was related to transportation.Conclusions These findings highlight the need to make prehabilitation programs more patient-centered. This is critical when designing more effective therapeutic strategies tailored to meet patients' specific needs while overcoming program non-adherence.

Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone. The purpose of this study was to determine whether a weekly supervised exercise session could provide further benefit to our current prehabilition program, when comparing to standard post-surgical rehabilitation.A parallel-arm single-blind randomized control trial was conducted in patients scheduled for non-metastatic colorectal cancer resection. Patients were assigned to either a once weekly supervised prehabilitation (PREHAB+, n = 41) or standard rehabilitation (REHAB, n = 39) program. Both multimodal programs were home-based program and consisted of moderate intensity aerobic and resistance exercise, nutrition counseling with daily whey protein supplementation and anxiety-reduction strategies. Perioperative care was standardized for both groups as per enhanced recovery after surgery (ERASBoth groups were comparable for baseline walking capacity (PREHAB+: 448 m [IQR 375-525] vs. REHAB: 461 m [419-556], p=.775) and included a similar proportion of patients who improved walking capacity (20 m) during the preoperative period (PREHAB+: 54% vs. REHAB: 38%, p = .222). After surgery, changes in 6MWD were also similar in both groups. In PREHAB+, however, there was a significant association between physical activity energy expenditure and 6MWD (p .01). Previously inactive patients were more likely to improve functional capacity due to PREHAB+ (OR 7.07 [95% CI 1.10-45.51]).The addition of a weekly supervised exercise session to our current prehabilitation program did not further enhance postoperative walking capacity when compared to standard REHAB care. Sedentary patients, however, seemed more likely to benefit from PREHAB+. An association was found between energy spent in physical activity and 6MWD. This information is important to consider when designing cost-effective prehabilitation programs.

Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.

Colorectal cancer surgery results in considerable postoperative morbidity, mortality and reduced quality of life. As many patients will undergo additional (neo)adjuvant therapy, it is imperative that each individual optimize their physical function. To elucidate the potential of exercise in patient optimization, we investigated the evidence for an exercise program before and after surgical treatment in colorectal cancer patients. A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions, the guidelines of the Physical Therapy Journal and the PRISMA guidelines. No literature pertaining to exercise training during preoperative neoadjuvant treatment was found. Seven studies, investigating the effects of regular exercise during adjuvant chemotherapy for patients with colorectal cancer or a mixed population, were identified. A small effect (effect size (ES) 0.4) of endurance/interval training and strength training (ES 0.4) was found in two studies conducted in patients with colorectal and gastrointestinal cancer. In five studies that included a mixed population of cancer patients, interval training resulted in a large improvement (ES 1.5; P≤.05). Endurance training alone was found to increase both lower extremity strength and endurance capacity. The effects of strength training in the lower extremity are moderate, whereas, in the upper extremity, the increase is small. There is limited evidence available on exercise training during treatment in colorectal cancer patients. One study concluded exercise therapy may be beneficial for colorectal cancer patients during adjuvant treatment. The possible advantages of training during neoadjuvant treatment may be explored by prehabilitation trials.

Objective Depression and poor functional status (FS) frequently co-occur. Though both predict adverse surgical outcomes, research examining preoperative functional performance (FP; self-reported) and functional capacity (FC; performance-based) measures in depressed cancer patients is lacking. Prehabilitation, a preoperative intervention including exercise, nutrition, and stress-reduction, may improve FC; however, whether depressed patients benefit from this intervention remains unknown. The primary objectives were to (a) assess differences in FP and FC and (b) explore the impact of prehabilitation on FC in individuals with depressive symptoms versus those without. Method A secondary analysis was conducted on 172 colorectal cancer patients enrolled in three studies comparing prehabilitation with a control group (rehabilitation). Measures were collected at 4 weeks pre- and 8 weeks postoperatively. FP, FC, and psychological symptoms were assessed using the 36-Item Short Form Health Survey, Six-Minute Walk Distance (6MWD), and Hospital Anxiety and Depression Scale (HADS), respectively. Subjects were divided into three groups according to baseline psychological symptoms: no psychological-symptoms (HADS-N), anxiety-symptoms (HADS-A), or depressive-symptoms (HADS-D). Main objectives were tested using analyses of variance, chi-square tests, and multivariate logistic regression. Results At baseline, HADS-D reported lower FP, had shorter 6MWD, and a greater proportion walked ≤ 400 m. Prehabilitation was associated with significant improvements in 6MWD in HADS-D group but not in HADS-N or HADS-A groups. Conclusion Poorer FS was observed in subjects with depressive symptoms, and these subjects benefited most from prehabilitation intervention. Future research could examine whether severity of depression and co-occurrence of anxiety differentially impact FS and whether prehabilitation can improve psychological symptoms and quality of life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This review by a 10-member panel of experts in surgical prehabilitation addresses processes that may improve oncologic care. Surgical prehabilitation is the process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of surgical treatment. The panel focused on the current state-of-the-science and recommended future research that would help to identify the elements that enhance preoperative physical, nutritional, and psychological health in anticipation of surgery, mitigate the burden of disease, facilitate the return of patient health status to baseline values, decrease postoperative morbidity, and reduce health care costs.

High complication rates following colorectal surgery render many patients unable to fully regain functional capacity, thus seriously compromising quality of life. The aim of this study was to assess whether a 4-week trimodal prehabilitation program (exercise, nutritional supplementation, and counseling on relaxation techniques), implemented during the preoperative period, is sufficient to modify exercise behaviors and improve functional capacity of elderly patients scheduled for colorectal cancer surgery. Patients were assigned to either a prehabilitation (PREHAB; n = 57) or matched time control group (CTRL; n = 59). Over the 4-week period prior to surgery, patients in PREHAB participated in a trimodal prehabilitation program. Patients in CTRL received the same program but only postoperatively. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to measure physical activity levels, while the 6-min walk test (6MWT) was used for assessment of functional walking capacity. Measurements were collected at baseline and at the time of surgery. Over the preoperative period, patients in PREHAB significantly increased the amount of moderate- and vigorous-intensity physical activities that they performed. PREHAB patients also demonstrated a greater improvement in 6MWT compared to CTRL. At the time of surgery, a greater proportion of patients in PREHAB met current physical activity guidelines, as compared to CTRL. These findings highlight the positive effects of a trimodal prehabilitation program on patients’ physical activity levels and functional walking capacity and demonstrate that modifying exercise behaviors and improving physical function within the 4-week preoperative period are an achievable goal.

Objective The growing recognition of prehabilitation has caused an emerging paradigm shift in surgical cancer care and an integrated component of the cancer care continuum. This narrative review aims to update and inform the urological community of the potential of prehabilitation before radical cystectomy. Data Sources A nonsystematic narrative review was performed through a database search in PubMed, and CINAHL using the following search terms: enhanced recovery after surgery (ERAS); Frailty; Prehabilitation and/or Rehabilitation; Physical Activity and/or exercises; Nutrition; Nutritional Care; Smoking cessation; Alcohol cessation; Prevention; Supportive Care; and combined with Radical Cystectomy. Conclusion A multimodal and multi-professional approach during the preoperative period may offer an opportunity to preserve or enhance physiological integrity and optimize surgical recovery. Studies indicate a positive effect of prehabilitation on postoperative functional capacity and earlier return to daily activities and health related quality of life. Meaningful outcomes that reflect recovery from a patient's perspective and clinical outcome measures, as well as validating metrics, are necessary to establish whether prehabilitation diminish the risk of developing long-term disability in high-risk patients. Implications for Nursing Practice Uro-oncology nurses are at the forefront in every ERAS program and vital in screening patients ahead of surgery for common risk factors, current impairments, and limitations that can compromise baseline functional capacity. The growing movement to standardize clinical implementation of prehabilitation, indicate there is a clear need for further investigation, optimization of a multimodal approach and an open discussion between health care providers from different areas of expertise who might best support and promote these initiatives.

Background: Poor functional capacity (FC) is an independent predictor of postoperative morbidity. However, there is still a lack of evidence as to whether enhancing FC before surgery has a protective effect on postoperative complications. The purpose of this study was to determine whether an improvement in preoperative FC impacted positively on surgical morbidity. Methods: This was a secondary analysis of a cohort of patients who underwent colorectal resection for cancer under Enhanced Recovery After Surgery care. FC was assessed with the 6-min walk test, which measures the distance walked in 6 min (6MWD), at 4 weeks before surgery and again the day before. The study population was classified into two groups depending on whether participants achieved a significant improvement in FC preoperatively (defined as a preoperative 6MWD change ≥19 meters) or not (6MWD change Results: A total of 179 eligible adults were studied: 80 (44.7%) improved in 6MWD by ≥19 m preoperatively, and 99 (55.3%) did not. Subjects whose FC increased had lower CCI (0 [0–8.7] versus 8.7 [0–22.6], p = .022). Furthermore, they were less likely to have a severe complication (adjusted OR 0.28 (95% CI 0.11–0.74), p = .010), and to have an ED visit. Conclusion: Improved preoperative FC was independently associated with a lower risk of severe postoperative complications. Further investigation is required to establish a causative relationship conclusively.

Importance Research supports use of prehabilitation to optimize physical status before and after colorectal cancer resection, but its effect on postoperative complications remains unclear. Frail patients are a target for prehabilitation interventions owing to increased risk for poor postoperative outcomes. Objective To assess the extent to which a prehabilitation program affects 30-day postoperative complications in frail patients undergoing colorectal cancer resection compared with postoperative rehabilitation. Design, Setting, and Participants This single-blind, parallel-arm, superiority randomized clinical trial recruited patients undergoing colorectal cancer resection from September 7, 2015, through June 19, 2019. Patients were followed up for 4 weeks before surgery and 4 weeks after surgery at 2 university-affiliated tertiary hospitals. A total of 418 patients 65 years or older were assessed for eligibility. Of these, 298 patients were excluded (not frail [n = 290], unable to exercise [n = 3], and planned neoadjuvant treatment [n = 5]), and 120 frail patients (Fried Frailty Index,≥2) were randomized. Ten patients were excluded after randomization because they refused surgery (n = 3), died before surgery (n = 3), had no cancer (n = 1), had surgery without bowel resection (n = 1), or were switched to palliative care (n = 2). Hence, 110 patients were included in the intention-to-treat analysis (55 in the prehabilitation [Prehab] and 55 in the rehabilitation [Rehab] groups). Data were analyzed from July 25 through August 21, 2019. Interventions Multimodal program involving exercise, nutritional, and psychological interventions initiated before (Prehab group) or after (Rehab group) surgery. All patients were treated within a standardized enhanced recovery pathway. Main Outcomes and Measures The primary outcome included the Comprehensive Complications Index measured at 30 days after surgery. Secondary outcomes were 30-day overall and severe complications, primary and total length of hospital stay, 30-day emergency department visits and hospital readmissions, recovery of walking capacity, and patient-reported outcome measures. Results Of 110 patients randomized, mean (SD) age was 78 (7) years; 52 (47.3%) were men and 58 (52.7%) were women; 31 (28.2%) had rectal cancer; and 87 (79.1%) underwent minimally invasive surgery. There was no between-group difference in the primary outcome measure, 30-day Comprehensive Complications Index (adjusted mean difference, –3.2; 95% CI, –11.8 to 5.3;P = .45). Secondary outcome measures were also not different between groups. Conclusions and Relevance In frail patients undergoing colorectal cancer resection (predominantly minimally invasive) within an enhanced recovery pathway, a multimodal prehabilitation program did not affect postoperative outcomes. Alternative strategies should be considered to optimize treatment of frail patients preoperatively. Trial Registration ClinicalTrials.gov identifier:NCT02502760

BACKGROUND Exercise training is a component of the pre-habilitation program. While in one previous study the training was home-based, in a subsequent investigation it was supervised in hospital. The hypothesis of this secondary analysis of the two studies was to determine whether supervised exercise further accelerates the return to baseline walking ability. METHODS Data from two consecutive randomized control trials (RCT) comparing pre-habilitation to the rehabilitation of cancer patients scheduled for colorectal surgery were pooled for analysis. The interventions were similar and included home-based exercise training, nutritional counseling and protein supplementation, and relaxation techniques administered either before surgery (pre-habilitation) or after surgery (rehabilitation). Patients in the second RCT received additional supervised exercise sessions. Functional capacity was assessed with the 6-minute walk test (6 MWT) at baseline, before surgery, and at 4 and 8 weeks after surgery. Adjusted logistic regression was used to determine the improvement of the 6-minute walk distance (6MWD). RESULTS Baseline mean 6MWD of 63 patients in the supervised group was 465.1 m (SD, 115), and that of 77 patients in the nonsupervised group was 407.8 m (SD, 109) (P

The concept of preparing surgical candidates with various modalities designed to increase physical, physiological, metabolic, and psychosocial reserves is known as prehabilitation. Prehabilitation has garnered significant attention in recent years as evidence grows describing benefits to clinical and quality of life outcomes. Recent research examining hospital length of stay and readmission rates provides promising findings with respect to the value of prehabilitation in economic and sustainable healthcare models. The role of prehabilitation across the surgical experience exploits common surgical wait-times and the teachable moment that many patients experience upon the identification of a surgical requirement to improve the pre-, peri-, and postoperative experience. Prehabilitation incorporates numerous systemic and regional approaches to conditioning the surgical candidate. These include exercise, nutrition, education, and/or psychosocial approaches that are intended to improve preoperative fitness and preparedness. Importantly, this also promotes and facilitates health behaviour changes not only preoperatively but during the postoperative period and over the long-term. In this paper, we briefly review the historical and current perspectives on prehabilitation and comment on opportunities for greater clinical and empirical understanding in this field.

Patients who are elderly, malnourished, anxious, and have a low physical function before surgery are likely to have suboptimal recovery from cancer surgery. A multimodal prehabilitation program is proposed, consisting of exercise training and nutritional and psychological support, which increases physiologic reserve before the stress of surgery. This interventional approach seems to improve ability to undergo the stress of surgery and faster recovery. The integration of exercise, adequate nutrition, and psychosocial components, with medical and pharmacologic optimization in the presurgical period, deserves to receive more attention by clinicians to elucidate the most effective interventions.

Low-carbohydrate diets are considered to be an effective approach to weight loss and have, subsequently, grown in popularity. Despite the apparent health benefits that these diets may provide for insulin resistance, hypertension, and dyslipidemia, their implications on cardiomyocyte oxidative capacity have yet to be investigated. To evaluate the adaptations induced by a 6-week low-carbohydrate, high-fat (LCHF) diet on mitochondrial respiration, two groups of male mice were investigated: Apolipoprotein E-deficient mice on a LCHF diet (L-DIET) and apolipoprotein E-deficient mice on a regular rodent diet (CON). Heart tissue was extracted and used for high-resolution respirometry (HRR), while immunoblotting was performed to quantify mitochondrial density and complexes. The results demonstrate increased expression of all five mitochondrial subunits in the L-DIET group compared to control condition. Furthermore, HRR revealed increased efficiency of substrate consumption, implying augmented oxidative capacity in the L-DIET group. These findings further support the notion that cardiomyocytes prefer lipids as a primary fuel source, by demonstrating that the shift in metabolism caused by a LCHF diet facilitates such an environment. This provides important information regarding the effects of a LCHF on cardiomyocytes, especially when considering free radical production and heart dysfunction.

Atherosclerosis remains the leading cause of severe cardiovascular complications such as cardio- and cerebrovascular events. Given that prevention and early intervention play important roles in the reduction of cardiovascular complications associated with atherosclerosis, it is critical to better understand how to target the modifiable risk factors, such as diet, in order to best minimize their contributions to the development of the disease. Studies have shown that various dietary sources of protein can affect blood lipid levels, a modifiable risk factor for atherosclerosis, either positively or negatively. This clearly highlights that not all proteins are "created equal." For example, consumption of diets high in either animal- or vegetable-based sources of protein have resulted in varied and inconsistent effects on blood cholesterol levels, often depending on the amino acid composition of the protein and the species investigated. Careful consideration of the source of dietary protein may play an important role in the prevention of atherosclerosis and subsequent cardiovascular complications. Given the recent focus on high protein diets, an emphasis on controlled studies in the area is warranted. The goal of this review is to present the current state of the literature that examines the effects of casein, a commonly utilized animal-based protein, on blood cholesterol levels and the varying effects noted in both animals and humans.

Objective: The incidence of childhood obesity in North America and around the world has risen significantly over the past decade leaving clinicians constantly searching for effective weight loss strategies. Despite the growing popularity or carbohydrate restricted diets, consequences of long term use remain widely unknown. The objective of the current investigation is to evaluate the effects of LCHF diets on heart size and cardiac glycogen content in young mice. Methods: Young mice (age 21 d, n = 24) and mature mice (age 84 d, n = 18) were placed on either a LCHF diet, a WD diet or a control diet for 12 weeks. Activity levels, body weight, and glucose values were measured during the investigation. At the competition of the dietary intervention, wet heart weights were measured to compute the heart weight-to-tibia length ratio, cross sectional area was calculated and sections of cardiac tissue were stained with periodic acid and Schiff reagent to visualize glycogen. Results: No differences in activity levels or glucose measures were noted between groups. Mice following the LCHF diet displayed a smaller heart weight-to-tibia length ratio when compared to controls. The trend was observed in both young (p = 0.012) and mature (p = 0.024) mice. No differences in cross sectional area were detected. Cardiac tissue from mice consuming the LCHF diet had a reduced percentage of total area stained positive for glycogen when compared to mice following the WD diet (p = 0.016). Conclusions: A LCHF diet can lead to the development of a smaller heart in young and mature mice. Alterations in intercellular cardiac glycogen content may contribute to differences observed in heart weight. Cardiac restricted diets should be recommended with caution as long term cardiac developmental impairments are unknown.

Multimodal prehabilitation is a preoperative conditioning intervention in form of exercise, nutritional assessment, whey protein supplementation, and anxiety-coping technique. Despite recent evidence suggesting that prehabilitation could improve functional capacity in patients undergoing colorectal surgery for cancer, all studies were characterized by a relatively small sample size. The aim of this study was to confirm what was previously found in three small population trials.Data of 185 participants enrolled in a pilot single group study and two randomized control trials conducted at the McGill University Health Center from 2010 to 2015 were reanalyzed. Subjects performing trimodal prehabilitation (exercise, nutrition, and coping strategies for anxiety) were compared to the patients who underwent the trimodal program only after surgery (rehabilitation/control group). Functional capacity was assessed with the six-minute walk test (6MWT), a measure of the distance walked over six minutes (6MWD). A significant functional improvement was defined as an increase in 6MWD from baseline by at least 19 m. Changes in 6MWD before surgery, at four and eight weeks were compared between groups.Of the total study population, 113 subjects (61%) underwent prehabilitation. Changes in 6MWD in the prehabilitation group were higher compared to the rehabilitation/control group during the preoperative period {30.0 [standard deviation (SD) 46.7] m vs. -5.8 (SD 40.1) m, p 0.001}, at four weeks [-11.2 (SD 72) m vs. -72.5 (SD 129) m, p 0.01], and at eight weeks [17.0 (SD 84.0) m vs. -8.8 (SD 74.0) m, p = 0.047]. The proportion of subjects experiencing a significant preoperative improvement in physical fitness was higher in those patients who underwent prehabilitation [68 (60%) vs. 15 (21%), p 0.001].In large secondary analysis, multimodal prehabilitation resulted in greater improvement in walking capacity throughout the whole perioperative period when compared to rehabilitation started after surgery.

Traditional rehabilitative approaches to perioperative cancer care have focused on the postoperative period to facilitate the return to presurgical baseline conditions. However, there is some realization that the preoperative period can be a very effective time for intervention as the patients are more amenable to target their physiological condition to prepare to overcome the metabolic cost of the surgical stress.We undertook a narrative review of the current literature on surgical prehabilitation and discussed the current evidence of preoperative interventions before cancer surgery in order to increase physiological reserve before surgery and accelerate postoperative recovery.Published data indicate the positive impact of prehabilitation on postoperative functional capacity and return to daily activities. However, the current evidence on the impact on short- and long-term clinical outcome is limited, and more research needs to be conducted.Preliminary findings indicate that a group of interventions such as exercise, nutrition and anxiety reduction in the preoperative period can complement the enhanced recovery program and facilitate the return to baseline activities of daily living. It is not clear at this stage whether the preoperative increase in functional capacity mitigates the burden of postoperative morbidities and subsequent cancer therapies. Therefore, more research is warranted.

This review by a 10-member panel of experts in surgical prehabilitation addresses processes that may improve oncologic care. Surgical prehabilitation is the process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of surgical treatment. The panel focused on the current state-of-the-science and recommended future research that would help to identify the elements that enhance preoperative physical, nutritional, and psychological health in anticipation of surgery, mitigate the burden of disease, facilitate the return of patient health status to baseline values, decrease postoperative morbidity, and reduce health care costs.

summary Background & aims: Despite the descriptive presence of cancer cachexia (CC) in clinical practice, the underlying mechanisms and diagnostic definition have not been clearly identified. Recent work, attempting to establish diagnostic and staging criteria for CC, has identified IL-6 as a biomarker. This study aimed to investigate the clinical relevance of plasma levels of four pro-inflammatory cytokines (IL6, IL-1b, IL-8 and TNF-a) in advanced cancer patients (ACP) to further establish their potential in the diagnostic definition of CC. Methods: Blood was obtained from 83 ACP (47 male and 36 female, aged 34e85 years) and analyzed for white blood cells, lymphocytes, C-reactive protein, albumin and cytokines. Subjects completed questionnaires to establish weakness, loss of appetite, fatigue, quality of life and weight loss; completed tests to determine strength, body composition and sarcopenia; and consented to chart review to calculate survival and total days admitted to hospital. Results: This study shows that, in ACP, IL-1 b is better associated with clinical features of the cachectic condition, such as weakness, loss of appetite, weight loss and sarcopenia, than IL-6. Conclusion: IL-6 may not best represent the clinical correlates of CC in ACP. Additional cytokines should be considered in the definition of this condition.

Introduction Exercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent. Methods and analysis We will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4). The intervention consists of > 3 weeks of exercise prehabilitation (strength, aerobic and stretching). The primary outcome is the 6 min walk test at the first postoperative clinic visit. Secondary outcomes include the short physical performance battery, health-related quality of life, disability-free survival, complications and health resource utilisation. The primary outcome will be analysed by intention to treat using analysis of covariance. Outcomes up to 1 year after surgery will be ascertained through linkage to administrative data. Ethics and dissemination Ethical approval has been granted by our ethics review board (Protocol Approval #2016009–01H). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media. Trial registration number NCT02934230; Pre-results.

Patients with type 2 diabetes (T2DM) have an increased risk for cardiovascular disease. We examined the effects of 8 weeks of home-based rowing training (heart rate corresponding to 65-70% of VO(2 peak) ) on endothelial function and glucose clearance (local and systemic effects) in male subjects with T2DM (n=9) and matched controls (n=8). Before and after training (30 min every other day), all subjects underwent sequential graded brachial artery infusions of non-insulin vasodilators (acetylcholine; sodium nitroprusside; adenosine). Forearm blood flow was improved by training in controls (without and with insulin: P=0.003 and 0.05, respectively) but not in subjects with T2DM. Likewise, whole body glucose clearance increased in response to training in controls (P=0.05) but not in T2DM. However, in both groups, the capacity for local forearm glucose extraction (controls: P=0.001; T2DM: P=0.002) and clearance (controls: P

Aims: The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent disease. Methods: 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60 mg/min), endothelial independent (sodium nitroprusside: 1, 3, 10 mg/min) and partially endothelial mediated (adenosine: 50, 150, 500 mg/min) vasodilators. The protocol was repeated during a hyperinsulinemic clamp. Forearm blood flow and glucose extraction were measured at each dose of vasodilator (with/ without insulin). Measurements were also taken in the control arm, reflecting systemic insulin infusion only. Results: Non-insulin mediated increases in bulk forearm blood flow were similar in T2DM and CON. However, insulin mediated forearm blood flow responses and glucose extraction were lower in T2DM versus CON. Conclusion: The vasodilatory effect of insulin is impaired in T2DM although bulk flow capacity is maintained. Insulin mediated glucose extraction is reduced during concomitant maximal stimulation of forearm blood flow with endothelial-dependent vasodilators, despite maintaining flow. This is consistent with previous work that associates T2DM with impaired insulin mediated capillary recruitment.

Patients with T2DM have an increased risk of CVD. Prevention of CVD represents the major goal of all treatment of T2DM, and early intervention in those patients at particularly high risk is important.We measured the insulin sensitivity and plasma biomarkers of CVD to determine whether a home-based exercise training program improves biomarker levels and insulin sensitivity. Patients with T2DM (n=12), IGT (n=4) and healthy control subjects (n=9) were studied before and after eight weeks of exercise training by rowing ergometry at 65—70% of peak oxygen uptake. Conclusions: 1) patients with T2DM have elevated plasma concentrations of CVD biomarkers compared to the matched control and IGT groups; 2) a moderate to vigorous intensity home-based training program did not reduce plasma concentrations of these CVD markers; 3) insulin sensitivity improved as a result of exercise training in the control group, but not in the T2DM group.

ObjectiveIn obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic–euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males.DesignWe studied eight obese females and eight obese males (body mass index (BMI): 32.6±1.4 and 32.8±0.8 respectively, non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7±1.6 and 47.6±1.3 ml/kg min respectively, NS).MethodsEach subject underwent two hyperinsulinemic–euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp.ResultsThe lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46±10 and 60±4% respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (PP=0.01 respectively). Muscle ceramide, triacylglycerol (TAG), diacylglycerol (DAG), and glycogen content were similar between sexes and remained unchanged during the clamp and when exercise was superimposed.ConclusionsThe lipid-induced inhibition of glucose disposal is similar in obese females and males. However, obese females are more insulin sensitive compared with obese males (both during saline and lipid infusion), which is not due to differences in the concentration of the muscle lipid intermediates such as ceramide and DAG.

Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes.