Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.

Exploring sedentary behavior during neo- or adjuvant treatment in patients with cancer: A phenomenological study.

PURPOSE: Increased sedentary behavior during cancer treatment is common, which may have negative long-term health effects. Understanding patients' experience of sedentary behavior during neo- or adjuvant cancer treatment may be crucial in developing effective support for patients to reduce sedentary behavior. Therefore, the present study aimed to explore sedentary behavior in patients undergoing neo- or adjuvant cancer treatment. METHODS: Eleven interviews were conducted with patients undergoing treatment for breast, prostate, and colorectal cancer. Participants were recruited from a university hospital in Sweden. Interviews were analyzed phenomenologically, and the results were presented as descriptions of the phenomenon sedentary behavior. RESULTS: The overarching theme of sedentary behavior during cancer treatment was that sedentary behavior is experienced through being physically active or not. Furthermore, experiences of sedentary behavior increased with side effects and varied depending on the type and phase of cancer treatment, meaning that sedentary behavior is an adjustment to side effects. Additionally, sedentary behavior was influenced by life circumstances and social interaction, such as work status and having social support. Finally, sedentary behavior is influenced by strategies and motivations, such as the perceived benefits of physical activity and self-image. CONCLUSIONS: Sedentary behavior is difficult for patients to discern, which is why health care personnel may need to help patients by increasing awareness of the negative impact of sedentary behavior in a way that does not stigmatize patients. Furthermore, developing support that targets periods with more side effects and helping patients reduce sedentary behavior throughout changing life circumstances may be helpful.

The effect of internet-administered support (carer eSupport) on preparedness for caregiving in informal caregivers of patients with head and neck cancer compared with support as usual: a study protocol for a randomized controlled trial.

BACKGROUND: Informal caregivers (ICs) of patients with cancer provide essential and mainly uncompensated care. A self-perceived preparedness to care for the patient is associated with a lower caregiver burden, described as the extent to which caregiving is perceived as having adverse effects on IC functioning and well-being. ICs' well-being is associated with patient-perceived quality of care, suggesting that interventions to optimize ICs' health are essential in order to improve patient care. Head and neck cancer (HNC) is the seventh most common malignant disease in the world. The disease and its treatment have a significant negative impact on the patient's health and quality of life. Symptoms usually interfere with swallowing, food and fluid intake, breathing, speaking, and communication. ICs frequently manage patients' symptoms and side effects, especially problems related to nutrition and oral pain, without being properly prepared. Carer eSupport is an Internet-administered intervention, based on focus group discussions with ICs, developed in collaboration with ICs and healthcare professionals, tested for feasibility, and deemed feasible. This study protocol outlines the methods of investigating the effects of Carer eSupport plus support as usual (SAU) on self-reported preparedness for caregiving, caregiver burden, and well-being in the ICs of patients with HNC, compared with ICs receiving SAU only. METHODS AND ANALYSIS: In this randomized controlled trial, 110 ICs of patients with HNC, undergoing radiotherapy combined with surgery and/or medical oncological treatment, will be randomized (1:1) to Carer eSupport plus SAU or SAU only. Data will be collected at baseline (before randomization), post-intervention (after 18 weeks), and 3 months after post-intervention. The primary outcome is self-reported preparedness for caregiving. Secondary outcomes are self-reported caregiver burden, anxiety, depression, and health-related quality of life. The effect of Carer eSupport plus SAU on preparedness for caregiving and secondary outcomes, compared with SAU only, will be evaluated by intention to treat analyses using linear regression models, mixed-model regression, or analysis of covariance. DISCUSSION: If proven effective, Carer eSupport has the potential to significantly improve ICs' preparedness for caregiving and their wellbeing, thereby improving patient-perceived quality of care and patient wellbeing. TRIAL REGISTRATION: ClinicalTrials.gov; NCT06307418, registered 12.03.2024 (https://clinicaltrials.gov/search? term=NCT06307418).

Does inflammation markers or treatment type moderate exercise intensity effects on changes in muscle strength in cancer survivors participating in a 6-month combined resistance- and endurance exercise program? Results from the Phys-Can trial.

BACKGROUND: Resistance exercise has a beneficial impact on physical function for patients receiving oncological treatment. However, there is an inter-individual variation in the response to exercise and the tolerability to high-intensity exercise. Identifying potential moderating factors, such as inflammation and treatment type, for changes in muscle strength is important to improve the effectiveness of exercise programs. Therefore, we aimed to investigate if inflammation and type of oncological treatment moderate the effects of exercise intensity (high vs. low-moderate) on muscular strength changes in patients with breast (BRCA) or prostate cancer (PRCA). METHODS: Participants with BRCA (n = 286) and PRCA (n = 65) from the Physical training and Cancer study (Phys-Can) were included in the present study. Participants performed a combined resistance- and endurance exercise program during six months, at either high or low-moderate intensity. Separate regression models were estimated for each cancer type, with and without interaction terms. Moderators included in the models were treatment type (i.e., neo/adjuvant chemotherapy-yes/no for BRCA, adjuvant androgen deprivation therapy (ADT)-yes/no for PRCA)), and inflammation (interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα)) at follow-up. RESULTS: For BRCA, neither IL6 (b = 2.469, 95% CI [- 7.614, 12.552]) nor TNFα (b = 0.036, 95% CI [- 6.345, 6.418]) levels moderated the effect of exercise intensity on muscle strength change. The same was observed for chemotherapy treatment (b = 4.893, 95% CI [- 2.938, 12.724]). Similarly, for PRCA, the effect of exercise intensity on muscle strength change was not moderated by IL6 (b = - 1.423, 95% CI [- 17.894, 15.048]) and TNFα (b = - 1.905, 95% CI [- 8.542, 4.732]) levels, nor by ADT (b = - 0.180, 95% CI [- 11.201, 10.841]). CONCLUSIONS: The effect of exercise intensity on muscle strength is not moderated by TNFα, IL6, neo/adjuvant chemotherapy, or ADT, and therefore cannot explain any intra-variation of training response regarding exercise intensity (e.g., strength gain) for BRCA or PRCA in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02473003.

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

BACKGROUND: Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. METHODS: This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. RESULTS: An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20 weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). CONCLUSIONS: This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

The Phys-Can study: meaningful and challenging - supervising physical exercise in a community-based setting for persons undergoing curative oncological treatment.

Introduction: Supervised exercise may improve physical function and quality of life during oncological treatment. Providing supervised exercise to all patients at hospitals may be impractical, with community-based settings (e.g. public gyms) as a possible alternative. To facilitate implementation, knowledge about the experiences of professionals who deliver exercise programs in community-based settings is crucial.Objective: To explore how physical therapists and personal trainers experience supervising exercise in a community-based setting for persons undergoing curative oncological treatment. Methods: Nine physical therapists and two personal trainers (coaches) were interviewed individually. The semi-structured interviews lasted 33-67 minutes and were analyzed using thematic analysis. Results: Two main themes emerged: "A meaningful task" and "A challenging task," with nine sub-themes. The coaches experienced supervising exercise for persons undergoing treatment as meaningful, as they became a link between oncology care and health promotion. They grew more confident in the role and ascertained that exercising during treatment was feasible. Challenges included managing side effects of treatment and contradictory information from oncology care staff at hospitals, advising patients not to exercise.Conclusion: Supervising exercise for persons undergoing oncological treatment in a community-based setting may be highly rewarding for professionals who deliver exercise programs, which is promising for implementation. However, patients receive contradictory information about exercise, which may prevent physical activity. Also, supervising exercise for persons undergoing oncological treatment requires skills training; this is suggested for inclusion in educational programs for physical therapists and others. Future research should focus on strategies for cooperation between oncology care and health promotion.

Making a business case in healthcare: the value of careful consideration.

A well thought-out business case offers an opportunity for clinicians to bring about evidenced-based change in clinical practice. It is a powerful tool that can have a significant impact on healthcare services and patient outcomes, while also offering desirable solutions to the NHS, which is facing growing healthcare demands on increasingly limited resources. The role of a business case is to justify the need for change, argue its value, gain support from leadership and illustrate how it can be sustainably implemented. This article guides clinicians through the process of producing a successful business case using the five-case model, which can be applied to the majority of improvement projects or services in healthcare settings. Clinicians might use this guide to support the development of a case to make a change in their own workplace or to help them take a full part in wider system changes.

Effects of heavy-load resistance training during (neo-)adjuvant chemotherapy on muscle cellular outcomes in women with breast cancer.

INTRODUCTION: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness. METHODS: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group.The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations. TRIAL REGISTRATION NUMBER: NCT04586517.

Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment.

Exercise training has been hypothesized to lower the inflammatory burden for patients with cancer, but the role of exercise intensity is unknown. To this end, we compared the effects of high-intensity (HI) and low-to-moderate intensity (LMI) exercise on markers of inflammation in patients with curable breast, prostate and colorectal cancer undergoing primary adjuvant cancer treatment in a secondary analysis of the Phys-Can randomized trial (NCT02473003). Sub-group analyses focused on patients with breast cancer undergoing chemotherapy. Patients performed 6 months of combined aerobic and resistance exercise on either HI or LMI during and after primary adjuvant cancer treatment. Plasma taken at baseline, immediately post-treatment and post-intervention was analyzed for levels of interleukin 1 beta (IL1B), IL6, IL8, IL10, tumor-necrosis factor alpha (TNFA) and C-reactive protein (CRP). Intention-to-treat analyses of 394 participants revealed no significant between-group differences. Regardless of exercise intensity, significant increases of IL6, IL8, IL10 and TNFA post-treatment followed by significant declines, except for IL8, until post-intervention were observed with no difference for CRP or IL1B. Subgroup analyses of 154 patients with breast cancer undergoing chemotherapy revealed that CRP (estimated mean difference (95% CI): 0.59 (0.33; 1.06); P = 0.101) and TNFA (EMD (95% CI): 0.88 (0.77; 1); P = 0.053) increased less with HI exercise post-treatment compared to LMI. Exploratory cytokine co-regulation analysis revealed no difference between the groups. In patients with breast cancer undergoing chemotherapy, HI exercise resulted in a lesser increase of CRP and TNFA immediately post-treatment compared to LMI, potentially protecting against chemotherapy-related inflammation.

Does exercise intensity matter for fatigue during (neo-)adjuvant cancer treatment? The Phys-Can randomized clinical trial.

Exercise during cancer treatment improves cancer-related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high- vs low-to-moderate-intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo-)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo-)adjuvant treatment were randomized to high intensity (n = 144), low-to-moderate intensity (n = 144), high intensity with BCS (n = 144) or low-to-moderate intensity with BCS (n = 145). The 6-month exercise intervention included supervised resistance training and home-based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4-20), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F, score range 0-52). Multiple linear regression for main factorial effects was performed according to intention-to-treat, with post-intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high- vs low-to-moderate-intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference -1.05 [95% CI: -1.85, -0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo-)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high- or low-to-moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well-controlled exercise interventions.

Is it safe to exercise during oncological treatment? A study of adverse events during endurance and resistance training - data from the Phys-Can study.

INTRODUCTION: Few studies have systematically evaluated the risk of adverse events (AEs) among persons exercising during oncological treatment. We aimed to describe incidence and types of AEs during exercise for persons undergoing oncological treatment, and associations to exercise intensity, exercise adherence, chemotherapy treatment, initial aerobic fitness. A second aim was to compare incidence of lymphedema, periphery inserted central catheter (PICC) complications, and other new medical conditions (any illness or injury occurred during the exercise trial) between high-intensity vs low-to-moderate exercise and usual care (UC). METHODS: This descriptive, comparative study was based on data from an observational study including patients in an UC setting (n = 90) and a randomized exercise trial (n = 577) in which participants exercised at high-intensity (HI) or low-moderate intensity (LMI). Persons with breast, prostate, or colorectal cancer undergoing neo/adjuvant treatment were included. AEs were reported by exercise coaches, participants, and identified in medical records, as were lymphedema, PICC-complications, and new medical conditions. RESULTS: Coaches reported AEs for 20% of the participants, while 28% of participants self-reported AEs. The most common coach- and participant reported AEs were musculoskeletal and the majority (97%) were considered minor. HI had higher likelihood of AEs than LMI, according to both coaches (OR: 1.9 [95%CI 1.16-3.21], p=.011) and participants (OR: 3.36 [95%CI 2.00-5.62], ≤.001). Lymphedema rates were low (4-9%) and PICC complications ranged from 15% in LMI to 23% in UC and there were no statistically significant differences between HI, LMI, and UC. There were no statistically significant differences between HI and LMI regarding new medical conditions. CONCLUSIONS: Exercise during treatment is safe for these patient groups in this setting, even HI exercise can be recommended if no medical contraindications are present. Similar to healthy populations, a higher risk of having minor AEs when exercising at HI in comparison to LMI may exist.

The Phys-Can observational study: adjuvant chemotherapy is associated with a reduction whereas physical activity level before start of treatment is associated with maintenance of maximal oxygen uptake in patients with cancer.

BACKGROUND: Adjuvant therapy may cause multiple sideeffects on long term health, including reduced cardiorespiratory fitness (CRF) in patients with breast cancer (1, 2). However, there is currently limited knowledge regarding the effect of different types of adjuvant cancer treatment on CRF in other cancer populations. The primary objective of the present study was to assess whether previously known correlates (age, diagnosis, initial CRF, physical activity level), type of adjuvant treatment and cancer-related fatigue were associated with changes in V ˙ O 2 max in patients with breast, prostate or colorectal cancer. METHODS: Prospective study with two time points of assessment, 85 patients scheduled for adjuvant cancer treatment were included. Cardiorespiratory fitness was assessed by V ˙ O 2 max during a maximal incremental exercise test on a treadmill before start of adjuvant therapy and again six months later. Physical activity level was recorded with a physical activity monitor (Sense Wear™ Mini) at baseline as average minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Physical fatigue at baseline was reported using the Multidimensional Fatigue Inventory-20 questionaire. RESULTS: In multivariate linear regression analysis, 30 min higher daily MVPA at baseline was associated with a 5% higher V ˙ O 2 max at six months follow up when adjusted for adjuvant treatment (P = 0.010). Patients receiving adjuvant chemotherapy had a mean decline in V ˙ O 2 max of 10% (- 19, - 1; 95% confidence interval) compared to patients receiving adjuvant endocrine treatment (P = 0.028). Adjuvant radiotherapy, fatigue, age and diagnosis were not significantly associated with changes in V ˙ O 2 max . CONCLUSION: The results of the present study indicate that adjuvant chemotherapy is associated with a subsequent reduction in V ˙ O 2 max in patients with cancer whereas MVPA before start of adjuvant treatment is positively associated with a higher V ˙ O 2 max after end of adjuvant treatment.

Weighted species richness outperforms species richness as predictor of biotic resistance.

The species richness hypothesis, which predicts that species-rich communities should be better at resisting invasions than species-poor communities, has been empirically tested many times and is often poorly supported. In this study, we contrast the species richness hypothesis with four alternative hypotheses with the aim of finding better descriptors of invasion resistance. These alternative hypotheses state that resistance to invasions is determined by abiotic conditions, community saturation (i.e., the number of resident species relative to the maximum number of species that can be supported), presence/absence of key species, or weighted species richness. Weighted species richness is a weighted sum of the number of species, where each species' weight describes its contribution to resistance. We tested these hypotheses using data on the success of 571 introductions of four freshwater fish species into lakes throughout Sweden, i.e., Arctic char (Salvelinus alpinus), tench (Tinca tinca), zander (Sander lucioperca), and whitefish (Coregonus lavaretus). We found that weighted species richness best predicted invasion success. The weights describing the contribution of each resident species to community resistance varied considerably in both strength and sign. Positive resistance weights, which indicate that species repel invaders, were as common as negative resistance weights, which indicate facilitative interactions. This result can be contrasted with the implicit assumption of the original species richness hypothesis, that all resident species have negative effects on invader success. We argue that this assumption is unlikely to be true in natural communities, and thus that we expect that weighted species richness is a better predictor of invader success than the actual number of resident species.

Strong invaders are strong defenders - implications for the resistance of invaded communities.

Many ecosystems receive a steady stream of non-native species. How biotic resistance develops over time in these ecosystems will depend on how established invaders contribute to subsequent resistance. If invasion success and defence capacity (i.e. contribution to resistance) are correlated, then community resistance should increase as species accumulate. If successful invaders also cause most impact (through replacing native species with low defence capacity) then the effect will be even stronger. If successful invaders instead have weak defence capacity or even facilitative attributes, then resistance should decrease with time, as proposed by the invasional meltdown hypothesis. We analysed 1157 introductions of freshwater fish in Swedish lakes and found that species' invasion success was positively correlated with their defence capacity and impact, suggesting that these communities will develop stronger resistance over time. These insights can be used to identify scenarios where invading species are expected to cause large impact.

Perceived barriers to and facilitators of being physically active during adjuvant cancer treatment.

OBJECTIVE: The aim was to describe cancer patients' perceived barriers and facilitators of physical activity during adjuvant cancer treatment. METHODS: Semi-structured focus group interviews were conducted with patients with breast cancer (n=9) and colorectal cancer (n=1) and prostate cancer (n=8) undergoing adjuvant cancer treatment. To capture perceived barriers and facilitators before starting treatment, individual interviews with women with breast cancer (n=5) were also conducted. 23 patients in total, were interviewed, and the transcribed interviews were analysed with qualitative content analysis. RESULTS: Three categories emerged: "Physical and emotional barriers"-addresses experiences of side-effects, co-morbid conditions and emotional barriers, preventing physical activity (PA). "Perspective and attitudes"-how self-efficacy, self-image, preference, concerns, expectations, experience and new perspective regarding one's health influencing PA. "Support and practicalities"-addresses needs of support and information and how practicalities could be a barrier to PA. CONCLUSIONS: Several barriers were side effects of oncological treatment, which can be alleviated by PA. Another barrier was concerns regarding safety of PA during treatment. Communicating benefits and safety of PA to cancer patients early as possible after diagnosis might be beneficial. PRACTICE IMPLICATIONS: Information about PA from health care staff should be given early after diagnosis and as a part of standard care.

Glycosynthase activity of hybrid aspen xyloglucan endo-transglycosylase PttXET16-34 nucleophile mutants.

Glycosynthases are active-site mutants of glycoside hydrolases that catalyse glycosyl transfer using suitable activated donor substrates without competing product hydrolysis (S. M. Hancock, M. D. Vaughan and S. G. Withers, Curr. Opin. Chem. Biol., 2006, 10, 509-519). Site-directed mutagenesis of the catalytic nucleophile, Glu-85, of a Populus tremula x tremuloides xyloglucan endo-transglycosylase (PttXET16-34, EC 2.4.1.207) into alanine, glycine, and serine yielded enzymes with glycosynthase activity. Product analysis indicated that PttXET16-34 E85A in particular was able to catalyse regio- and stereospecific homo- and hetero-condensations of alpha-xylogluco-oligosaccharyl fluoride donors XXXGalphaF and XLLGalphaF to produce xyloglucans with regular sidechain substitution patterns. This substrate promiscuity contrasts that of the Humicola insolens Cel7B E197A glycosynthase, which was not able to polymerise the di-galactosylated substrate XLLGalphaF. The production of the PttXET16-34 E85A xyloglucosynthase thus expands the repertoire of glycosynthases to include those capable of synthesising structurally homogenenous xyloglucans for applications.