MULTIPLE ENZYME CHANGES IN THE PLASMA OF NORMAL AND TUMOR-BEARING MICE FOLLOWING INFECTION WITH THE LACTIC DEHYDROGENASE AGENT

Within 72 hours after injection of the LDH agent into normal mice, five (LDH, ICDH, MDH, PHI, and GOT) out of the seven plasma enzymes studied were elevated. This elevation persisted for the duration of the experiment. Alkaline phosphatase and aldolase were not elevated. Plasma from mice bearing tumor SS-70429 and infected with the LDH agent showed 7 times more LDH, 8 times more ICDH, and 4 times more MDH activity than the plasma from mice with the same tumor but uninfected. The plasma aldolase activity from the infected tumor-bearing animal was approximately the same as that from the uninfected tumor-bearing animal. Somewhat similar results, but lower in magnitude, were found with mice bearing mammary carcinoma C3HBA. The early rise in plasma enzyme activity (LDH, MDH, ICDH) prior to the actual appearance of the tumor was shown to be due not to the tumor, but to the LDH agent. Uninfected tumor-bearing mice showed a late increase in plasma enzyme activity which appeared to be related to tumor growth. The findings reported above suggest that contamination with the LDH agent may have been responsible for much of the increased plasma enzyme activity previously attributed to the tumor

Is it feasible to conduct a randomised controlled trial of pretransplant exercise (prehabilitation) for patients with multiple myeloma awaiting autologous haematopoietic stem cell transplantation? Protocol for the PREeMPT study

Introduction While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition. Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation—exercise before treatment—has been shown to be effective in other disease areas. To date there has been no research into prehabilitation in patients with myeloma awaiting transplantation treatment. Our objective is to determine whether it is feasible to conduct a randomised controlled trial into pretransplant exercise for patients with multiple myeloma who are awaiting autologous stem-cell transplantation. Methods and analysis This mixed methods study identifies patients with diagnosis of multiple myeloma who have been assigned to the autologous transplantation list and invites them to participate in six weekly sessions of individualised, supervised exercise while awaiting transplantation. Quantitative data to determine feasibility targets include rates of recruitment, adherence and adverse events, and outcome measures including 6 min walking distance test and quality of life. Qualitative interviews are undertaken with a purposive sample of patients to capture their experiences of the study and the intervention. Ethics and dissemination Ethics committee approval has been obtained. Dissemination will be through open-access publications and presentations and will seek to reach multiprofessional bases as well as patients and carer groups, addressing the widespread interest in this area of research. Trial registration number NCT03135925; Pre-results

Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Gadolinium enhancement on high-resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta-analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. METHODS AND RESULTS: We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random-effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI-detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between-study heterogeneity using the Cochrane Q test and publication bias using the Begg-Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1-28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. CONCLUSIONS: Intracranial plaque enhancement on high-resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology.National Institutes of Health/National Institute of Neurological Disorders and Stroke (Grant ID: K23NS082367), National Institutes of Health/ National Center for Advancing Translational Sciences (Grant ID: KL2TR000458)This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/JAHA.116.00381

Evaluation of a city-wide physical activity pathway for people affected by cancer: the Active Everyday service

Purpose: The primary goal of this article is to present an evaluation of a UK-based city-wide physical activity pathway for patients with a cancer diagnosis, the Active Everyday service. Active Everyday was a co-produced physical activity service for people affected by cancer. The service was underpinned by a behaviour change care pathway model developed by Macmillan Cancer Support charity. Methods: This was a retrospective evaluation assessing physical activity levels and changes to outcome measures (fatigue, perceived health, and self-efficacy) over 6 months. Each participant self-reported their levels of physical activity for the previous 7 days at three-time points: baseline (T1), at 12-week exit from the scheme (T2), and at 6-month follow-up (T3). Results: The Active Everyday service received 395 referrals, of which 252 attended a baseline assessment. Participants’ fatigue and self-efficacy improved between T1 and T2 and T1 and T3. Perceived health improved across all time points. Participant exercise levels showed significant differences between T1 and T2. Conclusion: The service, provided over 3 years, resulted in positive health and wellbeing outcomes in people affected by cancer who engaged in the service. Future services must routinely include exercise referrals/prescriptions as a standard part of care to help engage inactive individuals. Services should focus on targeted promotion to people from ethnic minority groups, and a wide socioeconomic population

Should Healthcare Organisations Offer Ongoing Rehabilitation Services for Patients Undergoing Haematopoietic Cell Transplant? A Narrative Review

Purpose: Hematopoietic stem cell transplant (HSCT) patients can suffer from long-term transplant-related complications that affect their quality of life and daily activities. This study, a narrative review, aims to report the impact of HCT complications, the benefits of rehabilitation intervention, the need for long-term care and highlights the research gap in clinical trials involving rehabilitation. Design/methodology/approach: A comprehensive search strategy was performed on several databases to look for relevant articles published from 1998 to 2018. Articles published in English with the following terms were used: hematopoietic stem cell transplant, chronic graft-versus-host disease, rehabilitation, exercise, physical therapy, occupational therapy. A patient/population, intervention, comparison, and outcomes (PICO) framework was employed to ensure that the search strategies were structured and precise. Study year, design, outcome, intervention, sample demographics, setting and study results were extracted. Findings: Of the 1,411 records identified, 51 studies underwent title/abstract screening for appropriateness, 30 were reviewed in full, and 19 studies were included in the review. The review found that, for the majority of patients who underwent HSCT and developed treatment-related complications, rehabilitation exercises had a positive impact on their overall quality of life. However, exercise prescription in this patient group has not always reflected the scientific approach; there is a lack of high-quality clinical trials in general. The review also highlights the need to educate healthcare policymakers and insurance companies responsible for rationing services to recognise the importance of offering long-term follow-up care for this patient group, including rehabilitation services. Practical implications: A large number of HSCT patients require long-term follow-up from a multidisciplinary team, including rehabilitation specialists. It is important for healthcare policymakers and insurance companies to recognise this need and take the necessary steps to ensure that HSCT patients receive adequate long-term care. This paper also highlights the urgent need for high-quality rehabilitation trials to demonstrate the feasibility and importance of rehabilitation teams. Originality/value: Healthcare policymakers and insurance companies need to recognise that transplant patients need ongoing physiotherapy for early identification of any functional impairments and appropriate timely intervention

Time to act: the challenges of working during and after cancer, initiatives in research and practice

Time to act: the challenges of working during and after cancer, initiatives in research and practic

A continuous infusion of a minor histocompatibility antigen-immunodominant peptide induces a delay of male skin graft rejection.

We previously reported that an inhibition of antigen-specific Interferon-gamma release and cytotoxicity occurs after a continuous infusion of an HY immunodominant peptide although this treatment is not able to cause a significant delay of male skin grafts rejection. In vivo administration of high doses of an HY peptide, through mini-osmotic pumps, in naïve female mice was used to study the effects on the male skin grafts rejection. A continuous infusion of 1mg of an HY peptide induces a significant delay of male skin graft rejection. In vitro HY-specific Interferon-gamma release was inhibited adding peptide-specific suppressor cells: the ability to inhibit Interferon-gamma release was evident when two HY peptides were present on the same dendritic cells indicating that the suppressor cells exert "linked-suppression". The phenotype of the suppressor cells is CD8(+)CD28(-) and these cells express more CD62 ligand and FOXP3 than controls. Suppressor cells were able to cause a significant delay of rejection of male skin grafts when injected in naive female mice. The inhibitory effects of these suppressor cells seem to be due to the impairment of antigen presentation; down-regulation of B7 molecules on dendritic cells occurred. Taken all together, our data demonstrate that a continuous infusion of an immunodominant HY peptide induces a T CD8 suppressor subset able to inhibit immune responses to male tissues and cells

The development of a theory and evidence-based intervention to aid implementation of exercise into the prostate cancer care pathway with a focus on healthcare professional behaviour, the STAMINA trial

Abstract: Background: Twice-weekly supervised aerobic and resistance exercise for 12 weeks reduces fatigue and improves quality of life in men on Androgen Deprivation Therapy for prostate cancer. Despite the National Institute for Health and Care Excellence (NICE) proposing this as standard of care, it does not routinely take place in practice. Healthcare professionals are in a prime position to deliver and integrate these recommendations. A change in the behaviour of clinical teams is therefore required. In this paper, we describe the development of a training package for healthcare professionals using theory and evidence to promote delivery of such recommendations as standard care. Methods: The intervention development process was guided by the Medical Research Council guidance for complex interventions and the Behaviour Change Wheel. Target behaviours were identified from the literature and thirty-five prostate cancer care healthcare professionals (including oncologists, consultant urologists, clinical nurse specialists, physiotherapists, general practitioners and commissioners) were interviewed to understand influences on these behaviours. The Theoretical Domains Framework was used to identify theoretical constructs for change. Behaviour change techniques were selected based on theory and evidence and were translated into intervention content. The intervention was refined with the input of stakeholders including healthcare professionals, patients, and exercise professionals in the form of rehearsal deliveries, focus groups and a workshop. Results: Seven modifiable healthcare professional target behaviours were identified to support the delivery of the NICE recommendations including identifying eligible patients suitable for exercise, recommending exercise, providing information, exercise referral, providing support and interpret and feedback on progress. Ten domains from the Theoretical Domain’s Framework were identified as necessary for change, including improving knowledge and skills, addressing beliefs about consequences, and targeting social influences. These were targeted through twenty-two behaviour change techniques delivered in a half-day, interactive training package. Based on initial feedback from stakeholders, the intervention was refined in preparation for evaluation. Conclusions: We designed an intervention based on theory, evidence, and stakeholder feedback to promote and support the delivery of NICE recommendations. Future work will aim to test this training package in a multi-centre randomised trial. If proven effective, the development and training package will provide a template for replication in other clinical populations, where exercise has proven efficacy but is insufficiently implemented