Introduction In patients with non-small cell lung cancer (NSCLC), the prognostic significance of the tumor microenvironment (TME) immune composition has been demonstrated using single or dual-marker staining on sequential tissue sections. While these studies show that relative abundance and localization of immune cells are important parameters, deeper analyses of the NSCLC TME are necessary to refine the potential application of these findings to clinical care. Currently, the complex spatial relationships between cells of the NSCLC TME and potential drivers contributing to its immunologic composition remain unknown. Methods We employed multispectral quantitative imaging on the lung adenocarcinoma TME in 153 patients with resected tumors. On a single slide per patient, we evaluated the TME with markers for CD3, CD8, CD14, CD19, major histocompatibility complex II (MHCII), cytokeratin, and DAPI. Image analysis including tissue segmentation, phenotyping, and spatial localization were performed. Results Specimens where 5% or greater of lung cancer cells expressed MHCII (MHCIIhi TME) demonstrated increased levels of CD4+ and CD8+ T cell and CD14+ cell infiltration. In the MHCIIhi TME, the immune infiltrate was closer to cancer cells and expressed an activated phenotype. Morphologic image analysis revealed cancer cells in the MHCIIhi TME more frequently interfaced with CD4+ and CD8+ T cells. Patients with an MHCIIhi TME experienced improved overall survival (p=0.046). Conclusions Lung cancer cell-specific expression of MHCII associates with levels of immune cell infiltration, spatial localization, and activation status within the TME. This suggest cancer cell-specific expression of MHCII may represent a biomarker for the immune systems recognition and activation against the tumor.
ObjectiveTo assess the association of symptoms of depression and anxiety with sexual risk behaviour and history, among women and heterosexual men attending genitourinary medicine (GUM) clinics.MethodsAttitudes to and Understanding of Risk of Acquisition of HIV (AURAH) was a cross-sectional, self-administered questionnaire study recruited from 20 GUM clinics in England, 2013–2014. This analysis included women and heterosexual men. The prevalence of depression and anxiety symptoms was assessed. Modified Poisson regression was used to produce adjusted prevalence ratios (aPR) for the association of t demographic, socioeconomic and lifestyle factors with depression and anxiety, adjusted for gender, age, ethnicity, education level and study region. Among individuals reporting sex in the past 3 months, associations of depression and anxiety with sexual risk behaviour and history were assessed separately by gender, adjusted for age, ethnicity, study region, education and relationship status.ResultsQuestionnaires were completed by 676 women and 470 heterosexual men. Depression symptoms were reported by 100 (14.8%) women and 33 men (7.0%). Anxiety symptoms were reported by 79 women (11.7%) and 21 men (4.5%). Among women reporting recent sex, those with depression symptoms were more likely to report condomless sex with a non-regular partner, aPR 1.38 (1.07–1.77) and recent condomless sex with two or more partners, 1.80 (1.25–2.59). Women with anxiety symptoms more likely to report recent condomless sex with two or more partners, 1.68 (1.13–2.50), low self-efficacy for condom use, 1.54 (1.02–2.31) and STI diagnosis in the last year 1.51 (1.04–2.20). Among heterosexual men reporting recent sex, depression and anxiety symptoms were associated with low self-efficacy with condom use, 2.32 (1.29–4.19) for depression and 2.23 (1.26–3.94) for anxiety, but not with measures of condomless sex.DiscussionThe associations between psychological symptoms and sexual risk behaviours highlight the importance of holistic assessment of need by both general and sexual health clinicians. We highlight the challenge in delivering holistic care associated with fragmentation of sexual health services.
Objective: To determine the rate of uterine pathology in hysterectomies performed during surgery for treatment of uterovaginal prolapse. Methods:In this retrospective cohort study, we evaluated all patients undergoing hysterectomy during treatment of uterovaginal prolapse at a single academic institution from 2008 to 2013. Demographics, risk factors for uterine malignancy, operative data, and pathology reports were reviewed. Patients with history of concerning uterine pathology were excluded.Results: 339 subjects were included; none were excluded. Mean age of patients undergoing hysterectomy was 63.2 years with 85.5% post-menopausal. Mean BMI was 27 kg/m 2 and mean uterine weight was 71 grams. Abnormal pathology was identified in 0.8% (3/339) subjects: complex atypical hyperplasia (1), grade 1 endometrial adenocarcinoma (1), and low-grade B-cell lymphoma (1). 49% of specimens contained fibroids and no sarcomas were identified. Total hysterectomy was performed in 88%. 12% (40/339) underwent supracervical hysterectomy with morcellation. One specimen with abnormal pathology (complex atypical hyperplasia) was morcellated. Patients undergoing procedures requiring morcellation were younger (57.3 vs. 63.3, p=.001, 95%CI 2.52, 9.52) and less likely to be postmenopausal (69% vs. 88%, p=.021, 95%CI .067, .300). Risk factors for uterine malignancy were not different between groups. Conclusions:We found a low rate of incidental uterine pathology in hysterectomy specimens from prolapse surgery. Half of uterine specimens had leiomyomas. Specimens with fibroids had a higher mean weight than leiomyoma-free specimens. Risk factors for cancers among patients undergoing morcellation versus intact removal were not different. Further study is needed to clarify the role of morcellation in this low-risk population.
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