Retention rates and reasons for non-retention in exercise oncology trials in the post-treatment phase-a systematic review.

PURPOSE: Retention is a key marker of trial success. Poor retention can induce bias, reduce statistical power and minimise the validity of trials. This review examined retention rates in exercise trials in cancer survivors, reasons for non-retention and retention strategies utilised. METHODS: A systematic review was conducted using a predefined search strategy in EMBASE RCTs, MEDLINE OVID, CINAHL, Web of Science-Core Collection and Cochrane Central Register of Controlled Trials (CENTRAL). The search was conducted on 27/03/2023. Title and abstract screening, full text review and data extraction were completed in duplicate. RESULTS: Of 17,524 studies identified, 67 trials involving 6093 participants were included. The median overall retention rate immediately post-intervention was 89.85%, range (52.94-100%) and mean 87.36% (standard deviation 9.89%). Trials involving colorectal cancer survivors only had the highest median retention rate (94.61%), followed by breast (92.74%), prostate (86.00%) and haematological cancers (85.49%). Studies involving mixed cancer cohorts had the lowest retention rate (80.18%). The most common retention strategies were wait-list control groups, regular check-ins/reminders and free exercise equipment. Common reasons for non-retention were lost to follow-up, health problems, personal reasons including family/work commitments and travel burden, and disease progression. CONCLUSIONS: Retention rates in exercise oncology trials are approximately 90% immediately post-interventions. Our previous work highlighted variable suboptimal recruitment rates of median 38% (range 0.52-100%). Recruitment rather than retention should be prioritised for methodology research in exercise oncology. IMPLICATIONS FOR CANCER SURVIVORS: Optimising the quality of exercise oncology trials is critical to informing high quality survivorship care. PROSPERO registration number: CRD42023421359.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Effect of in-water administration of quorum system inhibitors in broilers' productive performance and intestinal microbiome in a mild necrotic enteritis challenge.

The poultry industry has been facing the impact of necrotic enteritis (NE), a disease caused by the bacterium Clostridium perfringens producing the haemolytic toxin NetB. NE severity may vary from mild clinical to prominent enteric signs causing reduced growth rates and affecting feed conversion ratio. NetB production is controlled by the Agr-like quorum-sensing (QS) system, which coordinates virulence gene expression in response to bacterial cell density. In this study, the peptide-containing cell-free spent media (CFSM) from Enterococcus faecium was tested in NE challenged broilers in two battery cage and one floor pen studies. Results showed a significant reduction of NE mortality. Metagenomic sequencing of the jejunum microbiome revealed no impact of the CFSM on the microbial community, and growth of C. perfringens was unaffected by CFSM in vitro. The expression of QS-controlled virulence genes netB, plc and pfoA was found to be significantly repressed by CFSM during the mid-logarithmic stage of C. perfringens growth and this corresponded with a significant decrease in haemolytic activity. Purified fractions of CFSM containing bioactive peptides were found to cause reduced haemolysis. These results showed that bioactive peptides reduce NE mortality in broilers by interfering with the QS system of C. perfringens and reducing bacterial virulence. Furthermore, the microbiome of C. perfringens-challenged broilers is not affected by quorum sensing inhibitor containing CFSM.

[Interest of iDAScore (intelligent Data Analysis Score) for embryo selection in routine IVF laboratory practice: Results of a preliminary study]. / Intérêt de l'iDAScore (intelligent Data Analysis Score) dans la pratique quotidienne d'un laboratoire de FIV pour la sélection embryonnaire : résultats d'une étude préliminaire.

INTRODUCTION: Embryo selection is a major challenge in ART, especially since the generalization of single embryo transfer, and its optimization could lead to the improvement of clinical results in IVF. Recently, several Artificial Intelligence (AI) models, based on deep-learning such as iDAScore, have been developed. These models, trained on time-lapse videos of embryos with known implantation data, can predict the probability of pregnancy for a given embryo, allowing automatization and standardization in embryo selection. MATERIAL AND METHODS: In this study, we have compared the hierarchical categorization of 311 D5 blastocysts of iDAScore v1.0 and the embryologists of our unit. These 311 D5 blastocysts have been classified as top (70.1%), good (Q+: 10.6%) and poor (Q-: 19.3%) quality by embryologists according to Gardner classification. Median iDAScores were [9.9-8.4],]8.4-7.5] and]7.5-2.1] for top, good and poor-quality blastocysts respectively. RESULTS: We observed a significantly concordant categorization between iDAScore and embryologists for top, good and poor-quality blastocysts (respectively, 89.5, 36.4 and 48.3%, P < 10-4). Moreover, the hierarchical categorization of the three best blastocysts between iDAScore and the embryologists was as follow: 1st rank: 71.9%; 2nd rank: 61.6%; 3rd rank: 56.8% (P=0.07). One hundred and fifty-one blastocysts with known implantation data were analyzed. The iDAScore of blastocysts that implanted was significantly higher than those that did not implant (implantation+: 9.10±0.57; implantation-: 8.70±0.95, P=0.003). CONCLUSION: This preliminary study shows that iDAScore is able to perform a reproducible, reliable and immediate hierarchical classification of blastocysts. Moreover, this tool can identify the blastocysts with the highest implantation potential. If these results confirmed on a larger scale of embryos and patients, IA could revolutionize IVF laboratories by standardizing embryo hierarchical selection.

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

Altered inflammasome activation in neonatal encephalopathy persists in childhood.

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1ß, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1ß and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1ß gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.

Modification of Proteins by Metabolites in Immunity.

Immunometabolism has emerged as a key focus for immunologists, with metabolic change in immune cells becoming as important a determinant for specific immune effector responses as discrete signaling pathways. A key output for these changes involves post-translational modification (PTM) of proteins by metabolites. Products of glycolysis and Krebs cycle pathways can mediate these events, as can lipids, amino acids, and polyamines. A rich and diverse set of PTMs in macrophages and T cells has been uncovered, altering phenotype and modulating immunity and inflammation in different contexts. We review the recent findings in this area and speculate whether they could be of use in the effort to develop therapeutics for immune-related diseases.

Posterior reversible encephalopathy syndrome with Lilliputian hallucinations secondary to Takayasu's arteritis.

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare complication of Takayasu's Arteritis. A 54-year-old, right-handed woman presented with Lilliputian visual hallucinations, postprandial abdominal pain, blurred vision and headaches. She then had a tonic-clonic seizure. Neuroimaging revealed characteristic white matter oedema of the occipital lobes, in keeping with PRES. Renal infarcts and abnormalities of the abdominal aorta, subclavian, mesenteric, and internal carotid arteries were demonstrated on further imaging. The combination of hypertension, absent peripheral pulses, postprandial claudication, and imaging abnormalities of the aorta as well as its branches, lead to the diagnosis of PRES secondary to Takayasu's Arteritis. Treatment with oral steroids resulted in complete resolution of the patient's symptoms and abnormalities found on CT and MRI brain imaging. Takayasu's Arteritis is a rare vasculitis, more common in women and PRES is an unusual complication. Symptoms of PRES may include headache, seizures, hallucinations, confusion, and altered consciousness. Risk factors for PRES include; pregnancy, immunosuppression, renal disease, hypertension and rheumatological disorders. Vasogenic oedema in affected lobes, most often occipital, is characteristic of PRES on neuroimaging. Prompt treatment of PRES can avoid catastrophic consequences such as death and can achieve complete resolution of symptoms and imaging abnormalities.

Cardiopulmonary Exercise Testing in Oesophagogastric Surgery: a Systematic Review.

BACKGROUND: Cardiopulmonary exercise testing (CPX) can objectively measure fitness and oxygen uptake at anaerobic threshold. The relationship between fitness and postoperative outcomes after upper gastro-intestinal surgery is unclear. The aim of the present review is to assess the prognostic ability of CPX in predicting postoperative outcome associated with oesophagogastric surgery. METHODS: Relevant studies were identified through a systematic search of EMBASE, Medline, CINAHL, Cochrane Library, and Web of Science to July 2019. The eligibility criteria for studies included prognostic studies of upper gastro-intestinal surgery among adult populations using a preoperative CPX and measurement of postoperative outcome (mortality or morbidity or length of stay). Risk of bias was assessed using the QUIPS Quality in Prognostic Studies validated tool. RESULTS: Thirteen papers with a total of 1735 participants were included in data extraction. A total of 7 studies examined the association between CPX variables and postoperative mortality. Patients undergoing gastro-intestinal surgery with lower anaerobic threshold values were found to have an increased risk of postoperative mortality. Similarly, a lower rate of oxygen consumption was found to be associated with higher mortality. There was conflicting evidence regarding the association between CPX variables and postoperative morbidity. The evidence did not demonstrate any association between preoperative CPX variables and hospital length of stay. CONCLUSION: Studies report an association between CPX variables and postoperative mortality; however, there is conflicting evidence regarding the association between CPX variables and postoperative morbidity.

Evaluation of protective and immune responses following vaccination with recombinant MIP and CPAF from Chlamydia abortus as novel vaccines for enzootic abortion of ewes.

MIP and CPAF from Chlamydia have been shown to be effective in inducing immune responses important in clearing chlamydial infections. This study evaluates the protection conferred by MIP and CPAF as novel vaccines in pregnant C. abortus challenged ewes. Fifty C. abortus sero-negative sheep were randomly allocated into 5 groups of 10 according to the treatment they were to receive (1) 100 µg of MBP-MIP (2) 100 µg CPAF (3) 50 µg MBP-MIP and 50 µg CPAF (4) Tris-buffer (negative control) (5) Enzovax (positive control). Booster inoculations were administered 3 weeks after primary inoculations. Blood samples were taken pre-vaccination and weekly for 5 weeks. Five months after vaccination the ewes were mated. Pregnant ewes were then challenged on day 90 of gestation. Blood samples taken at four time-points post challenge were analysed for IFNγ levels, TNFα and IL-10 expression and anti-chlamydial antibody levels. Vaginal swabs, placental and foetal tissue and bacterial shedding were analysed using qPCR to quantify levels of C. abortus. Enzovax was 100% effective with no abortions occurring. The MIP/CPAF combined vaccine offered the greatest protection of the novel vaccines with 67% of ewes giving birth to one or more live lambs equating to a 50% vaccine efficacy rate. MIP and CPAF administered singly did not confer protection. Enzovax and MIP/CPAF vaccinated ewes had longer gestations and lambs with higher birth weights than negative control ewes. Aborting ewes shed higher numbers of C. abortus than ewes that had live lambs, all vaccinated ewes demonstrated lower levels of bacterial shedding than negative control ewes with Enzovax ewes shedding significantly fewer bacteria. Ewes that went on to abort had significantly higher levels of IFNγ and IL-10 at day 35 post challenge and significantly higher levels of anti-chlamydial antibodies at 24 h post lambing compared to ewes that had live lambs.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Effect of preoperative inspiratory muscle training on physical functioning following esophagectomy.

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.

Comparison of three commercial serological tests for the detection of Chlamydia abortus infection in ewes.

BACKGROUND: 20.9% of diagnosable abortions in Ireland in 2015 were caused by Chlamydia abortus infection. Abortion usually occurs in the last 2-3 weeks of gestation, and up to 30% of ewes may be affected in naïve flocks. Serological diagnosis of EAE in flocks using LPS or whole bacteria as antigens is often hindered by cross reactions with C. pecorum. Although the complement fixation test is the official test for diagnosis of EAE, more sensitive and specific ELISA based tests have been developed. This study aimed to compare three commercial ELISA kits to detect C. abortus antibodies in ewes and to determine which of the kits had the highest sensitivity. The IDvet kit utilises a MOMP peptide antigen, the MVD-Enfer kit is based on a POMP90-3 antigen while the LSI kit plates are coated with chlamydial LPS. The study also aimed to examine the potential of these ELISAs to distinguish infected animals that go on to abort compared to those that have live lambs. Ewes were vaccinated with either a commercial live vaccine (n = 10) or Tris-buffer sham inoculation (n = 9) 5 months prior to gestation, these ewes were then challenged with C. abortus (1 × 106 IFU/ml) on day 90 of gestation. Sera were collected at pre-vaccination, 14 days post vaccination, 35 days post vaccination, pre-challenge, 35 days post challenge and 3 weeks post lambing/abortion (~ 70 days post challenge) and tested using the 3 aforementioned ELISAs to determine if one ELISA was more sensitive at detecting circulating anti-chlamydial antibodies. RESULTS: Sensitivity was highest with the LSI test kit at 94.74%, followed by the MVD-Enfer and IDvet kits, at 78.95 and 73.68% respectively. Ewes vaccinated with Enzovax became seropositive at 14 days post vaccination with all kits. Following challenge at day 90 of gestation, antibody titres steadily rose in all groups of ewes. With all ELISA kits, antibody levels were higher in ewes that aborted compared to ewes that had live lambs at 35 days post challenge and three weeks post lambing, and statistically significantly higher antibody levels were recorded in ewes that aborted compared to ewes that had live lambs using the MVD-ENFER ELISA at three weeks post lambing (P = 0.0482). CONCLUSIONS: The LSI assay was the most sensitive out of the three kits tested in this study, when sera were tested at three weeks post lambing. As the LPS used in this kit is cross-reactive with all chlamydia, it is good for identifying flocks infected with any chlamydial species, but it is not considered specific for C. abortus. Furthermore, antibody levels were higher in ewes that aborted compared to ewes that had live lambs, at both 35 days post challenge and at three weeks post lambing. Future work should include evaluation of a larger number of sera at a wider range of time-points as well as an estimation of the specificity of commercially available assays.

A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT).

BACKGROUND: Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. OBJECTIVES: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX. METHODS: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day). RESULTS: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation. CONCLUSIONS: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.

Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

OBJECTIVES: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1ß (IL-1ß) have been implicated in pancreatic ß cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic ß cell death could allow for selective T2D treatment without compromising all IL-1ß-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic ß cell death, thereby preventing the onset of T2D. METHODS: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic ß cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. RESULTS: MCC950 was a potent inhibitor of NLRP3-induced IL-1ß in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1ß. CONCLUSIONS: NLRP3 driven-pancreatic IL-1ß inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer.

PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Physical activity and advanced cancer: the views of oncology and palliative care physicians in Ireland.

BACKGROUND: Physical activity (PA) levels play an important role in maintaining the quality of life and enhancing the physical function of advanced cancer patients. A brief exercise prompt by physicians can increase PA levels of patients diagnosed with cancer. AIMS: This study explores the views of Irish oncology and palliative care physicians towards PA for patients with advanced cancer. METHODS: A web-based survey with closed- and open-ended questions was used to explore physicians' views. The survey presented a Likert-style questionnaire and open text responses to two patient case studies. Quantitative data were analysed using descriptive statistics, and qualitative data were analysed using content analysis. RESULTS: Forty participants completed the study, a response rate of 41%. Responding physicians acknowledged the importance of physical activity for patients with advanced cancer. Twenty-six physicians (67%) agreed that patients look to them for PA recommendations and 30 physicians (77%) indicated a need for more information on providing PA recommendations. Case study responses highlighted concerns relating to PA prescription for patients with bone metastases including the aggravation of symptom control and increased fracture risk. CONCLUSIONS: The results of this study identify a need for physician education on providing PA recommendations for patients with advanced cancer. Concerns over the prescription of PA to patients with bone metastases highlight the need to disseminate the evidence on the benefits of PA for patients with metastatic cancer to healthcare professionals.

The views of patients with metastatic prostate cancer towards physical activity: a qualitative exploration.

PURPOSE: Patients with metastatic cancer can experience debilitating symptoms, which may influence attitudes towards and engagement in physical activity. This study aimed to examine the attitudes of patients living with metastatic prostate cancer towards physical activity. MATERIALS AND METHODS: Semi-structured interviews were completed with male patients living with metastatic prostate cancer. Interviews included eight questions related to patients' attitudes towards physical activity. Content analysis was conducted on the transcribed interview data. Twenty men with metastatic prostate cancer (mean age 71 ± 8.5 years; body mass index 30.19 ± 5.37 kg/cm2) and associated bone metastases (55% with > 2 regions affected) participated in the study. RESULTS: Men's views towards physical activity were coded into the following major themes: (1) barriers to physical activity, (2) benefits of physical activity, (3) a reduction in physical activity levels post diagnosis and (4) social support for physical activity. Symptoms of metastatic prostate cancer and treatment side effects including pain and fatigue negatively influenced activity participation. In addition, many generic barriers to physical activity were described such as bad weather and a lack of suitable facilities for exercising in rural areas. CONCLUSION: Men living with metastatic prostate cancer have unique needs regarding physical activity related to symptoms of both their cancer and cancer treatment. There is a need to increase prompts that encourage those with metastatic prostate cancer to maintain/increase physical activity levels post diagnosis. Given the individualised needs of this patient group, referral to a cancer exercise specialist should be considered for prescription of tailored physical activity programmes. TRIAL REGISTRATION: Clinicaltrials.gov NLM Identifier: NCT02453139.

Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-ß and cognitive function in APP/PS1 mice.

Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impact on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity. Here, we examined the effect of the small molecule inhibitor of the NLRP3 inflammasome, MCC950, on microglia in vitro and in vivo. The findings indicate that MCC950 inhibited LPS+Aß-induced caspase 1 activation in microglia and this was accompanied by IL-1ß release, without inducing pyroptosis. We demonstrate that MCC950 also inhibited inflammasome activation and microglial activation in the APP/PS1 mouse model of AD. Furthermore, MCC950 stimulated Aß phagocytosis in vitro, and it reduced Aß accumulation in APP/PS1 mice, which was associated with improved cognitive function. These data suggest that activation of the inflammasome contributes to amyloid accumulation and to the deterioration of neuronal function in APP/PS1 mice and demonstrate that blocking assembly of the inflammasome may prove to be a valuable strategy for attenuating changes that negatively impact on neuronal function.