The effect of age in the outcome and treatment of older women with ductal carcinoma in situ

AbstractThe effect of increasing age on outcomes and type of treatment given to older women with ductal carcinoma in situ (DCIS) was assessed. 646 women ≥60 years old (654 cases) receiving surgery for DCIS at Memorial Sloan-Kettering Cancer Center between 2000 and 2007 (8 bilateral) had wide local excision (WLE; 37%), WLE plus radiotherapy (WLE+RT; 41%), or mastectomy (22%). 45%, 38%, and 16% of patients 60–69 years, 70–79 years, and ≥80 years, respectively, received WLE+RT (P<0.001) and 25%, 20%, and 13%, received mastectomy, respectively (P<0.001). Age (P<0.001), grade (P<0.001), and necrosis (P<0.01) were highly associated with treatment. Four-year local recurrence was 3.6%. Overall local recurrence differed by treatment (mastectomy, 0%; WLE, 5%; WLE+RT, 4%; P<0.00001) but not age. It is possible to identify older women with DCIS in whom the risk of recurrence is acceptably low after WLE alone. WLE alone may be a viable treatment option for select older women with DCIS

Non-suicidal reasons for self-harm: a systematic review of self-reported accounts

Background: Self-harm is a major public health problem yet current healthcare provision is widely regarded as inadequate. One of the barriers to effective healthcare is the lack of a clear understanding of the functions self-harm may serve for the individual. The aim of this review is to identify first-hand accounts of the reasons for self-harm from the individual's perspective. Method: A systematic review of the literature reporting first-hand accounts of the reasons for self-harm other than intent to die. A thematic analysis and ‘best fit' framework synthesis was undertaken to classify the responses. Results: The most widely researched non-suicidal reasons for self-harm were dealing with distress and exerting interpersonal influence. However, many first-hand accounts included reasons such as self-validation, and self-harm to achieve a personal sense of mastery, which suggests individuals thought there were positive or adaptive functions of the act not based only on its social effects. Limitations: Associations with different sub-population characteristics or with the method of harm were not available from most studies included in the analysis. Conclusions: Our review identified a number of themes that are relatively neglected in discussions about self-harm, which we summarised as self-harm as a positive experience and defining the self. These self-reported “positive” reasons may be important in understanding and responding especially to repeated acts of self-harm

Metabolic support of regulatory T cells by lactic acid

Regulatory T (Treg) cells, although vital for immune homeostasis, also represent a major barrier to anti-cancer immunity, as the tumor microenvironment (TME) promotes the recruitment, differentiation, and activity of these cells1,2. Tumor cells show deregulated metabolism, leading to a metabolite-depleted, hypoxic and acidic TME3, which places infiltrating effector T cells in competition with the tumor for metabolites and impairs their function4–6. At the same time, Treg cells maintain a strong suppression of effector T cells within the TME7,8. As previous studies suggested that Treg cells possess a distinct metabolic profile from effector T cells9–11, we hypothesized that the altered metabolic landscape of the TME and increased activity of intratumoral Treg cells are linked. Here we show that Treg cells display broad heterogeneity in their metabolism of glucose within normal and transformed tissues and can engage an alternative metabolic pathway to maintain suppressive function and proliferation. Glucose uptake correlates with poorer suppressive function and long-term instability, and high-glucose conditions impair the function and stability of Treg cells in vitro. Treg cells instead upregulate pathways involved in the metabolism of the glycolytic by-product lactic acid. Treg cells withstand high-lactate conditions, and treatment with lactate prevents the destabilizing effects of high-glucose conditions, generating intermediates necessary for proliferation. Lactic acid also contributes directly to epigenetic modifications through histone lactylation which may support the expression of Treg cell signature genes. Deletion of MCT1—a lactate transporter—in Treg cells reveals that lactate uptake is dispensable for the function of peripheral Treg cells but required intratumorally, resulting in slowed tumor growth and an increased response to immunotherapy. Thus, Treg cells are metabolically flexible: they can use ‘alternative’ metabolites in the TME to maintain their suppressive identity. Further, our results suggest that tumors avoid destruction by not only depriving effector T cells of nutrients, but also metabolically supporting regulatory populations