MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE: To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN: We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS: MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION: Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The care of older cancer patients in the United Kingdom

The ageing population poses new challenges globally. Cancer care for older patients is one of these challenges, and it has a significant impact on societies. In the United Kingdom (UK), as the number of older cancer patients increases, the management of this group has become part of daily practice for most oncology teams in every geographical area. Older cancer patients are at a higher risk of both under- and over-treatment. Therefore, the assessment of a patient’s biological age and effective organ functional reserve becomes paramount. This may then guide treatment decisions by better estimating a prognosis and the risk-to-benefit ratio of a given therapy to anticipate and mitigate against potential toxicities/difficulties. Moreover, older cancer patients are often affected by geriatric syndromes and other issues that impact their overall health, function and quality of life. Comprehensive geriatric assessments offer an opportunity to identify and address health problems which may then optimise one’s fitness and well-being. Whilst it is widely accepted that older cancer patients may benefit from such an approach, resources are often scarce, and access to dedicated services and research remains limited to specific centres across the UK. The aim of this project is to map the current services and projects in the UK to learn from each other and shape the future direction of care of older patients with cancer

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients’ physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University’s Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level

Impact of a prehabilitation and recovery programme on emotional well-being in individuals undergoing cancer surgery: A multi-perspective qualitative study

Background: Prehabilitation and recovery programmes aim to optimise patients’ physical fitness and mental well-being before, during and after cancer treatment. This paper aimed to understand the impact of such a programme on emotional well-being in individuals undergoing cancer surgery. The programme was multi-modal, containing physical activity, well-being and nutritional support.Methods: Qualitative interviews were conducted with 16 individuals who participated in a prehabilitation and recovery programme. Twenty-four health care staff involved in referral completed an online survey. An inductive, thematic analysis was conducted, integrating perspectives of patients and staff, structured with the Framework approach.Results: Patients seemed to experience emotional benefits from the programme, appearing less anxious and more confident in their ability to cope with treatment. They seemed to value having something positive to focus on and control over an aspect of treatment. Ongoing, implicit psychological support provided by Exercise Specialists, who were perceived as expert, available and caring, seemed valued. Some patients appeared to appreciate opportunities to talk about cancer with peers and professionals. Discomfort with talking about cancer with other people, outside of the programme, was expressed.Conclusions: Participation in a prehabilitation and recovery programme appeared to yield valuable emotional well-being benefits, even without referral to specialist psychological support.<br/

Impact of a Best Practice Alert on the Implementation of Expedited Partner Therapy

Objectives: The objective of this study was to determine if an ED-based electronic health record (EHR) Best Practice Alert (BPA) increased the ordering of expedited partner therapy (EPT) for sexually transmitted infections (STI) in adult patients.Background: US EDs have reported increases in STI visits and positivity rates, mirroring record level increases in STI incidence in the general population. EPT is an evidence-based practice recommended by public health experts for treating sexual partners of STI patients. EDs typically evaluate patients for STIs without their sexual partner present, thereby providing opportunities for EPT. However, EPT is infrequently used in US EDs.Methods: This pilot study was part of a quality improvement initiative conducted between August and October 2021 in an academic tertiary care ED located in the Midwest. An EPT BPA was randomly displayed in the EHR to clinicians when they empirically treated adult ED patients for STIs with antibiotics. Differences in proportions of EPT ordering were calculated for STI visits between BPA exposed vs. unexposed, ED clinician type, and testing-confirmed vs. not confirmed STI status.Results: Of the 52 adult ED patients empirically treated for STIs during the study period, their mean age was 30 years old, 56% were female, 48% White and 40% Black, and 31% had Medicaid. Testing-confirmed STI prevalence was 27%. EPT was ordered less often during BPA unexposed (8%; 95% CI 1-25) than BPA exposed (42%; 95% CI 23-63) STI visits, for a mean difference of 35% (95% CI 13-56). EPT was ordered during 41% of STI visits involving residents, as compared to 7% of physician assistant visits (p=0.07). EPT was not ordered more often for testing-confirmed vs. not confirmed STI visits (21% vs. 26%; p=0.7).Conclusion: Displaying an EHR BPA greatly increased EPT ordering for patients empirically treated for STIs, although not consistently across all clinician types. Because suspected cases of STIs may be less common in some EDs depending on the populations they serve, BPAs may be a useful tool to bolster the implementation of EPT practices

Acceptability of prehabilitation for cancer surgery: a multi-perspective qualitative investigation of patient and ‘clinician’ experiences

Abstract Background ‘Prehabilitation’ interventions aim to enhance individuals’ physical fitness prior to cancer treatment, typically involve exercise training as a key component, and may continue to support physical activity, strength, and fitness during or after treatment. However, uptake of prehabilitation is variable. This study investigated how patients from diverse socio-economic status groups perceived an exemplar prehabilitation and recovery programme, aiming to understand factors impacting acceptability, engagement and referral. Methods This research was conducted in the context of the Prehab4Cancer and Recovery Programme, a prehabilitation and recovery programme available across Greater Manchester, UK. Qualitative, semi-structured phone/video-call interviews were conducted with 18 adult patient participants referred to the programme (16 ‘engagers’, 2 ‘non-engagers’; half the sample lived in localities with low socio-economic status scores). An online questionnaire with free-response and categorical-response questions was completed by 24 ‘clinician’ participants involved in referral (nurses, doctors and other staff roles). An inductive, multi-perspective, thematic analysis was performed, structured using the Framework approach. Results Discussing and referring patients to prehabilitation can be challenging due to large quantities of information for staff to cover, and for patients to absorb, around the time of diagnosis. The programme was highly valued by both participant groups; the belief that participation would improve recovery seemed a major motivator for engagement, and some ‘clinicians’ felt that prehabilitation should be treated as a routine part of treatment, or extended to support other patient groups. Engagers seemed to appreciate a supportive approach where they did not feel forced to do any activity and tailoring of the programme to meet individual needs and abilities was appreciated. Initial engagement could be daunting, but gaining experience with the programme seemed to increase confidence. Conclusions The prehabilitation programme was highly valued by engagers. Introducing prehabilitation at a challenging time means that personalised approaches might be needed to support engagement, or participation could be encouraged at a later time. Strategies to support individuals lacking in confidence, such as buddying, may be valuable. Study registration The study protocol was uploaded onto the Open Science Framework 24 September 2020 ( https://osf.io/347qj/ )