Understanding the performance-related psychological characteristics and skills of doctors: A sport psychology perspective.

INTRODUCTION: Doctors need to consistently maintain their clinical performance across a range of different situations by managing the stress response provoked by these situations. Six performance-related adaptive and maladaptive psychological characteristics and psychological skills can distinguish between how athletes manage their stress response and consistently maintain an optimal level of performance across a variety of situations. The aim of the study was to understand how the performance-related psychological characteristics and skills identified in athletes are applied by doctors. METHODS: An exploratory qualitative study was conducted with semi-structured interviews. A purposive sample of 10 doctors were interviewed and the data were analysed by template analysis. RESULTS: Doctors have similar performance-related psychological characteristics and skills as identified in athletes for managing their stress response to consistently maintain optimal clinical performance. The importance of maladaptive characteristics was also identified, especially in junior doctors. CONCLUSIONS: The findings of this pilot study can be used for informing the design of performance-related educational interventions for doctors to manage their stress response for consistently maintaining optimal clinical performance. An important consideration will need to be a focus on specific groups in their career journey and the development of a multi-dimensional, reflective, and problem-solving approach.

An overview and evaluation of the differential attainment champion role in the North West of England GP school.

BACKGROUND AND AIMS: In the Northwest of England, a national allocation of funding to minimise the effects of differential attainment has been used to support experienced GP educators to act as Differential Attainment Champions (DAC) since October 2021. An evaluation of the role's impact was undertaken. METHODS: The evaluation was designed to gather the views and experiences of DACs and their trainees via online semi-structured interviews during the first 12 months following establishment of the intervention programme. RESULTS: Thematic framework analysis identified three main themes: DACs' adaptive approach to support trainees; barriers to fulfilling the DAC role; and the positive impact of the DAC role on training. The following aspects of the DAC role worked well: the freedom to tailor support to the individual needs of the trainees; the targeted and proactive support early on in GP core training; the support of trainees in a wide range of areas including e-portfolio advice, examination preparation, and personal help. Trainees valued one-to-one support when needed. Reported improvements included: improved examination outcomes; portfolio engagement recognised in some cases by Annual Review of Competence Progression (ARCP) panels. CONCLUSIONS: The individualised and adaptive approach works well but it does mean it is difficult to quantify how many trainees can be supported by one DAC and their workload needs to be monitored.

Applying sport psychology in health professions education: A systematic review of performance mental skills training.

INTRODUCTION: Health professionals are expected to consistently perform to a high standard during a variety of challenging clinical situations, which can provoke stress and impair their performance. There is increasing interest in applying sport psychology training using performance mental skills (PMS) immediately before and during performance. METHODS: A systematic review of the main relevant databases was conducted with the aim to identify how PMS training (PMST) has been applied in health professions education and its outcomes. RESULTS: The 20 selected studies noted the potential for PMST to improve performance, especially for simulated situations. The key implementation components were a multimodal approach that targeted several PMS in combination and delivered face-to-face delivery in a group by a trainer with expertise in PMS. The average number of sessions was 5 and of 57 min duration, with structured learner guidance, an opportunity for practice of the PMS and a focus on application for transfer to another context. CONCLUSION: Future PMST can be informed by the key implementation components identified in the review but further design and development research is essential to close the gap in current understanding of the effectiveness of PMST and its key implementation components, especially in real-life situations.

Cancer-Associated Fibroblasts Suppress CD8+ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade.

Immune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination αCTLA4 and αPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathologic analyses demonstrating a relationship between CAF density and a CD8+ T-cell-excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of αSMA-expressing CAFs and impaired tumor progression in vivo. The addition of wild-type, but not Endo180-deficient, CAFs in coimplantation studies restricted CD8+ T-cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T-cell infiltration and enhanced sensitivity to ICB compared with tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors were associated with a poor response to αPD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy. SIGNIFICANCE: Paired syngeneic models help unravel the interplay between CAF and tumor immune evasion, highlighting the benefits of targeting fibroblast subpopulations to improve clinical responses to immunotherapy.

Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment.

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.

Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis.

Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.

Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.

Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed a pharmacogenomic analysis of MEKi-sensitive versus MEKi-resistant colorectal cancer cell lines. Strikingly, interferon- and inflammatory-related gene sets were enriched in cell lines exhibiting intrinsic and acquired resistance to MEK inhibition. The bromodomain inhibitor JQ1 suppressed interferon-stimulated gene (ISG) expression and in combination with MEK inhibitors displayed synergistic effects and induced apoptosis in MEKi-resistant colorectal cancer cell lines. ISG expression was confirmed in patient-derived organoid models, which displayed resistance to trametinib and were resensitized by JQ1 co-treatment. In in vivo models of colorectal cancer, combination treatment significantly suppressed tumor growth. Our findings provide a novel explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, known for its inflammatory nature. Moreover, the high expression of ISGs was associated with significantly reduced survival of colorectal cancer patients. Excitingly, we have identified novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer.

Correction: Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.

A correction to this paper has been published and can be accessed via a link at the top of the paper.