A single bout of vigorous intensity exercise enhances the efficacy of rituximab against human chronic lymphocytic leukaemia B-cells ex vivo.

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naïve CLL completed a bout of cycling 15 % above anaerobic threshold for âˆ¼ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3-CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells - independent of rituximab - was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy.

Harnessing the immunomodulatory effects of exercise to enhance the efficacy of monoclonal antibody therapies against B-cell haematological cancers: a narrative review.

Therapeutic monoclonal antibodies (mAbs) are standard care for many B-cell haematological cancers. The modes of action for these mAbs include: induction of cancer cell lysis by activating Fcγ-receptors on innate immune cells; opsonising target cells for antibody-dependent cellular cytotoxicity or phagocytosis, and/or triggering the classical complement pathway; the simultaneous binding of cancer cells with T-cells to create an immune synapse and activate perforin-mediated T-cell cytotoxicity against cancer cells; blockade of immune checkpoints to facilitate T-cell cytotoxicity against immunogenic cancer cell clones; and direct delivery of cytotoxic agents via internalisation of mAbs by target cells. While treatment regimens comprising mAb therapy can lead to durable anti-cancer responses, disease relapse is common due to failure of mAb therapy to eradicate minimal residual disease. Factors that limit mAb efficacy include: suboptimal effector cell frequencies, overt immune exhaustion and/or immune anergy, and survival of diffusely spread tumour cells in different stromal niches. In this review, we discuss how immunomodulatory changes arising from exposure to structured bouts of acute exercise might improve mAb treatment efficacy by augmenting (i) antibody-dependent cellular cytotoxicity, (ii) antibody-dependent cellular phagocytosis, (iii) complement-dependent cytotoxicity, (iv) T-cell cytotoxicity, and (v) direct delivery of cytotoxic agents.

Patient-clinician dynamics in remote consultations: a qualitative study of cardiology and rheumatology outpatient clinics in the UK.

OBJECTIVE: Explore the experiences of patients and clinicians in rheumatology and cardiology outpatient clinics during the first year of the COVID-19 pandemic, focusing on the impact of remote consultations on interpersonal dynamics. DESIGN: Qualitative study using semistructured interviews, conducted between February and June 2021. SETTING: The rheumatology and cardiology departments of a general hospital in England, UK. PARTICIPANTS: All clinicians and a convenience sample of 100 patients in each department who had taken part in a remote consultation in the past month were invited to take part. Twenty-five interviews were conducted (13 with patients, 12 with clinicians). RESULTS: Three themes were developed through the analysis: adapting to the dynamics of remote consultations, impact on the patient's experience and impact on the clinician's experience. The majority of remote consultations experienced by both patients and clinicians had been via telephone. Both clinicians and patients found remote consultations to be more business-like and focused, with the absence of pauses restricting time for reflection. For patients with stable, well-managed conditions, remote consultations were felt to be appropriate and could be more convenient than in-person consultations. However, the loss of visual cues meant some patients felt they could not give a holistic view of their condition and limited clinicians' ability to gather and convey information. Clinicians adjusted their approach by asking more questions, checking understanding more frequently and expressing empathy verbally, but felt patients still shared fewer concerns remotely than in person; a perception with which patients concurred. CONCLUSIONS: These findings highlight the importance of ensuring, for each patient, that remote care is appropriate. Future research should focus on developing ways to support both clinicians and patients to gather and provide all information necessary during remote consultations, to enhance communication and trust.

"A disembodied voice over the telephone": a qualitative study of healthcare practitioners' experiences in geriatric medicine.

OBJECTIVES: This study explored the experience of delivering care remotely among practitioners in a UK geriatric medicine clinic. METHODS: Nine semi-structured interviews were conducted with consultants (n = 5), nurses (n = 2), a speech and language and an occupational therapist, and thematically analysed. RESULTS: Four themes developed; Challenges of remote consultations; Perceived advantages of remote consultations; Disruption of involvement of family members; Impact on care staff. Participants felt that rapport and trust had been more feasible to develop remotely than they had anticipated, although this was more challenging for new patients and those with cognitive or sensory impairments. While practitioners identified advantages of remote consultations, including involving relatives, saving time, and reducing anxiety, they also experienced disadvantages such as consultations feeling like a 'production line', missing visual cues and reduced privacy. Some participants felt their professional identity was threatened by the lack of face-to-face contact, linked to feeling that remote consultations are not suitable for frail older adults or those with cognitive deficits. DISCUSSION: Staff perceived barriers to remote consultations that went beyond practical concerns, and suggest support for building rapport, involving families, and protecting clinician identity and job satisfaction may be warranted.

The effects of exercise on complement system proteins in humans: a systematic scoping review.

BACKGROUND: The complement system is comprised of the classical, lectin and alternative pathways that result in the formation of: pro-inflammatory anaphylatoxins; opsonins that label cells for phagocytic removal; and, a membrane attack complex that directly lyses target cells. Complement-dependent cytotoxicity (CDC) - cell lysis triggered by complement protein C1q binding to the Fc region of antibodies bound to target cells - is another effector function of complement and a key mechanism-of-action of several monoclonal antibody therapies. At present, it is not well established how exercise affects complement system proteins in humans. METHODS: A systematic search was conducted to identify studies that included original data and investigated the association between soluble complement proteins in the blood of healthy humans, and: 1) an acute bout of exercise; 2) exercise training interventions; or, 3) measurements of habitual physical activity and fitness. RESULTS: 77 studies were eligible for inclusion in this review, which included a total of 10,236 participants, and 40 complement proteins and constituent fragments. Higher levels of exercise training and cardiorespiratory fitness were commonly associated with reduced C3 in blood. Additionally, muscle strength was negatively associated with C1q. Elevated C3a-des-Arg, C4a-des-Arg and C5a, lower C1-inhibitor, and unchanged C3 and C4 were reported immediately post-laboratory based exercise, compared to baseline. Whereas, ultra-endurance running and resistance training increased markers of the alternative (factor B and H), classical (C1s), and leptin (mannose binding lectin) pathways, as well as C3 and C6 family proteins, up to 72-h following exercise. Heterogeneity among studies may be due to discrepancies in blood sampling/handling procedures, analytical techniques, exercise interventions/measurements and fitness of included populations. CONCLUSIONS: Increased anaphylatoxins were observed immediately following an acute bout of exercise in a laboratory setting, whereas field-based exercise interventions of a longer duration (e.g. ultra-endurance running) or designed to elicit muscle damage (e.g. resistance training) increased complement proteins for up to 72-h. C3 in blood was mostly reduced by exercise training and associated with increased cardiorespiratory fitness, whereas C1q appeared to be negatively associated to muscle strength. Thus, both acute bouts of exercise and exercise training appear to modulate complement system proteins. Future research is needed to assess the clinical implications of these changes, for example on the efficacy of monoclonal antibody therapies dependent on CDC.

'You're kind of left to your own devices': a qualitative focus group study of patients with breast, prostate or blood cancer at a hospital in the South West of England, exploring their engagement with exercise and physical activity during cancer treatment and in the months following standard care.

OBJECTIVES: The aim of this study was to explore the experiences of patients with breast, prostate or blood cancer, regarding their (1) engagement with exercise and physical activity during treatment and in the months following standard care, and (2) the meanings attached to these lifestyle behaviours. DESIGN: A qualitative study using focus groups. The groups were audio recorded, transcribed and analysed using Framework analysis. SETTING: A hospital-based cancer treatment centre in the South-West of England. PARTICIPANTS: Eighteen people who had either completed treatment or were currently on maintenance therapy for breast, prostate or blood cancer (non-Hodgkin lymphoma or Hodgkin lymphoma). RESULTS: Participants reported treatment limiting their ability to engage in exercise and physical activity. However, participants were aware of the physiological, emotional and social benefits of exercise and expressed a desire to maintain a physically active lifestyle before, during and after treatment. They noted a lack of concrete guidance and appropriate exercise classes for people with cancer and felt poorly informed about the type, intensity, duration and frequency of exercise they should be undertaking. As such, participants reported making decisions on their own, relying on their intuition and listening to their bodies to gauge whether they were doing enough exercise (or not). CONCLUSIONS: Participants were aware of the benefits of a physically active lifestyle during and following cancer treatment, but were not familiar with exercise and physical activity guidelines for people living with and beyond cancer. There is a need for healthcare professionals, academics and policy makers to determine how exercise and physical activity can be supported in clinical settings in realistic and meaningful ways accommodating individual patient circumstances.

The experiences of cancer patients within the material hospital environment: Three ways that materiality is affective.

Improving the patient experience is widely recognised as an important goal in the delivery of high-quality healthcare. This study contributes to this goal with a particular focus on the role of the material hospital environment for patients being treated for cancer. Extending the burgeoning literature utilising materialist theoretical approaches in social science and medicine, we report on qualitative data with 18 participants who had received cancer treatment from one UK hospital. Our analysis offers a typology of ways in which the material hospital environment is affective: through patients' direct intra-actions with nonhuman materiality; through providing shared spaces within which human-human assemblages are actualised; and through being the material component of the practices of treatment. Within each process in this typology, the analysis highlights how the affective feeling states which play a critical role in patient wellbeing are in many ways contingent, fluid and context-sensitive. Amidst ambitions to improve the patient experience, these findings underline the significance of materialities of care and offer a broad explanatory typology with analytic and practical potential for healthcare staff, patient groups, architects and designers.

Acute aerobic exercise induces a preferential mobilisation of plasmacytoid dendritic cells into the peripheral blood in man.

Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise. Nine healthy males (age, 21.9 ±â€¯3.6 years; height, 177.8 ±â€¯5.4 cm; body mass, 78.9 ±â€¯10.8 kg; body mass index, 24.9 ±â€¯3.3 kg·m2; V̇O2 MAX, 41.5 ±â€¯5.1 mL·kg·min-1) cycled for 20 min at 80% V̇O2 MAX. Blood was sampled at baseline, during the final minute of exercise and 30 min later. Using flow cytometry, total DCs were defined as Lineage- (CD3, CD19, CD20, CD14, CD56) HLA-DR+ and subsequently identified as plasmacytoid DCs (CD303+) and myeloid DCs (CD303-). Myeloid DCs were analysed for expression of CD1c and CD141 to yield four sub-populations; CD1c-CD141+; CD1c+CD141+; CD1c+CD141- and CD1c-CD141-. Expression of CD205 was also analysed on all DC sub-populations to identify DCs capable of recognising apoptotic and necrotic cells. Total DCs increased by 150% during exercise (F(1,10) = 60; p < 0.05, η2 = 0.9). Plasmacytoid DCs mobilised to a greater magnitude than myeloid DCs (195 ±â€¯131% vs. 131 ±â€¯100%; p < 0.05). Among myeloid DCs, CD1c-CD141- cells showed the largest exercise-induced mobilisation (167 ±â€¯122%), with a stepwise pattern observed among the remaining sub-populations: CD1c+CD141- (79 ±â€¯50%), followed by CD1c+CD141+ (44 ±â€¯41%), with the smallest response shown by CD1c-CD141+ cells (23 ±â€¯54%) (p < 0.05). Among myeloid DCs, CD205- cells were the most exercise responsive. All DC subsets returned to resting levels within 30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferons against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy.

n-3 Fatty Acid Supplementation During 4 Weeks of Training Leads to Improved Anaerobic Endurance Capacity, but not Maximal Strength, Speed, or Power in Soccer Players.

Omega-3 fatty acid (n-3 FA) supplementation could promote adaptation to soccer-specific training. We examined the impact of a 4-week period of n-3 FA supplementation during training on adaptations in 1RM knee extensor strength, 20-m sprint speed, vertical jump power, and anaerobic endurance capacity (Yo-Yo test) in competitive soccer players. Twenty six soccer players were randomly assigned to one of two groups: n-3 FA supplementation (n-3 FA; n = 13) or placebo (n = 13). Both groups performed two experimental trial days. Assessments of physical function and respiratory function were conducted pre (PRE) and post (POST) supplementation. Training session intensity, competitive games and nutritional intake were monitored during the 4-week period. No differences were observed in respiratory measurements (FEV1, FVC) between groups. No main effect of treatment was observed for 1RM knee extensor strength, explosive leg power, or 20 m sprint performance, but strength improved as a result of the training period in both groups (p < .05). Yo-Yo test distance improved with training in the n-3 FA group only (p < .01). The mean difference (95% CI) in Yo-Yo test distance completed from PRE to POST was 203 (66-340) m for n-3 FA, and 62 (-94-217) m for placebo, with a moderate effect size (Cohen's d of 0.52). We conclude that 4 weeks of n-3 FA supplementation does not improve strength, power or speed assessments in competitive soccer players. However, the increase in anaerobic endurance capacity evident only in the n-3 FA treatment group suggests an interaction that requires further study.

Training status and sex influence on senescent T-lymphocyte redistribution in response to acute maximal exercise.

PURPOSE: Investigate training status and sex effects on the redistribution of senescent and naïve T-lymphocytes following acute exercise. METHODS: Sixteen (8 male, 8 female) trained (18.3±1.7yr) soccer players (Tr) and sixteen (8 male, 8 female) untrained (19.3±2.0yr) controls (UTr) performed a treadmill running test to volitional exhaustion. Blood lymphocytes were isolated before (Pre), immediately post, and 1-h post-exercise for assessment of cell surface expression of CD28 and CD57 on CD4(+) and CD8(+) T-lymphocyte subsets. Plasma was used to determine cytomegalovirus (CMV) serostatus. RESULTS: Exercise elicited a redistribution of T-lymphocyte subsets. Senescent CD4(+) and CD8(+) T-lymphocytes increased by 42.4% and 45.9% respectively, while naïve CD4(+) and CD8(+) T-lymphocytes decreased by 8.7% and 22.5% respectively in response to exercise. A main effect (P<0.05) of training status was observed for senescent CD4(+), CD8(+) and naïve CD8(+) T-lymphocytes: UTr had a higher proportion of senescent and a lower proportion of naïve CD8(+) T-lymphocytes than Tr. A main effect (P<0.05) of sex was observed in senescent CD4(+), CD8(+) and naïve CD4(+), CD8(+) T-lymphocytes. Males had a higher proportion of senescent and lower proportion of naïve T-lymphocytes than females. A sex-by-training status interaction (P<0.05) was observed for the senescent and naïve CD4(+) T-lymphocytes (but not CD8(+)) with the highest percentage of senescent and lowest percentage of naïve T-lymphocytes observed in UTr males. CMV exerted a significant main covariate effect (P<0.05) in the senescent and naïve (P<0.05) CD8(+) T-lymphocytes but not in the senescent and naïve CD4(+) T-lymphocytes. CONCLUSION: This study highlights important sex and training status differences in the senescent and naïve T-lymphocyte redistribution in response to exercise that warrants further investigation.