INTRODUCTION A comprehensive characterisation of the tumour microenvironment is lacking in neuroendocrine tumours (NETs), where programmed cell death-1 receptor-ligand (PD-1/PD-L1) inhibitors are undergoing efficacy testing. OBJECTIVE We investigated drivers of cancer-related immunosuppression across NETs of various sites and grade using multi-parameter immunohistochemistry and targeted transcriptomic profiling. METHODS Tissue microarrays (n=102) were stained for PD-L1 & 2, Indoleamine-deoxygenase-1 (IDO-1) and evaluated in relationship to functional characteristics of tumor-infiltrating T-lymphocytes (TILs) and biomarkers of hypoxia/angiogenesis. PD-L1 expression was tested in circulating tumour cell (CTCs, n=12) to evaluate its relationship with metastatic dissemination. RESULTS PD-L1 expression was highest in lung NETs (n=30, p=0.007), whereas PD-L2 was highest in pNETs (n=53, p less then 0.001) with no correlation with grade or hypoxia/angiogenesis. PD-L1+ NETs (n=26, 25%) had greater CD4+/FOXP3+ and CD8+/PD1+ TILs (p less then 0.001) and necrosis (p=0.02). CD4+/FOXP3+ infiltrate was highest PD-L1/IDO-1 co-expressing tumours (p=0.006). Grade 3 well-differentiated NETs had lower CD4+/FOXP3+ and CD8+/PD1+ TILs density (p less then 0.001) and Nanostring immune-profiling revealed enrichment of macrophage-related transcripts in cases with poorer prognosis. We identified PD-L1(+) CTC subpopulations in 75% of evaluated patients (n=12). CONCLUSIONS PD-L1 expression correlates with T-cell exhaustion independent of tumour hypoxia and is enhanced in a subpopulation of CTCs, suggesting its relevance to the progression of NETs. These findings support a potential therapeutic role for PD-L1 inhibitors in a subset of NETs. © 2020 S. Karger AG, Basel.BACKGROUND Skin cancer places a substantial burden on the health system in Australia. The modernisation of skin cancer prevention interventions by using social media may enhance their contemporary reach and relevance, especially among the youth. This study aimed to analyse Twitter posts in Australia to establish a baseline of skin cancer and sun-related communication trends. METHODS Tweets posted over the summer of 2018/2019 relating to relevant keywords and hashtags such as "slipslopslap" and "sunscreen" were analysed using quantitative and qualitative methods. The number of tweets, related communication patterns, and possible factors for sudden changes in tweet volume were studied. RESULTS Results showed that Australians are using Twitter to communicate about their sun-related and skin cancer experiences and to share advice and information on this matter. Overall, Australians use Twitter more frequently to talk about sunscreen (number of tweets between December 2018 and February 2019 = 5,842) and/or skin cancer (n = 3,936), but not so often to communicate about other sun-protective behaviours (n = 1,972) or skin cancer prevention campaigns (n = 108). The number of tweets is greatly affected by the increase in temperature. Celebrities, non-health-related organisations with a high number of followers, and individuals sharing their own skin cancer experiences achieve a substantial number of likes and retweets and thus influence on Twitter regarding skin cancer-related communication. CONCLUSIONS The results allow deeper understanding of important determinants for effective social media use for health promotion and public health messaging in the future. Linking tweets with temperature, sharing by celebrities or non-health-related organisations and individuals with a high following can all contribute to greater spread of skin cancer and sun-related messages. © 2020 S. Karger AG, Basel.INTRODUCTION Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma. Similarly, irinotecan-based therapy has marginal efficacy. We combined irinotecan plus a fluoropyrimidine with an anti-PD-1 antibody, nivolumab, with hopes of having a higher advantage for patients. OBJECTIVES Primary objective was to assess safety judged by toxicities, dose delays, or dose reductions. Secondary endpoints included the assessment of response, overall survival (OS), and progression-free survival (PFS). METHODS We treated 15 patients with this combination during July 2017 to April 2019. Patients were included if they had follow-up at our institution. RESULTS Median doses given were nivolumab 240 mg + irinotecan 120 mg/m2 + 5-FU 2,000 mg/m2 over 46-48 h (or capecitabine 1,250 mg/m2/day; 7 days on, 7 days off) given every 2 weeks. Median age of the patients was 55 years, and all patients had an ECOG performance status of 0-1. The patients had a median of 1 prior therapy. Slightly over half of the patients had PD-L1 expression. The median number of cycles was 7. Five patients (33%) had a dose delay or dose adjustment. The most common reason for dose delay or adjustment was grade 2 fatigue. Disease control (response or stability) on first scan was 73.3% (n = 11). Median PFS and OS for the entire group was 7 and 13.3 months, respectively. CONCLUSION In this small cohort of patients, we conclude that this combination is quite feasible and resulted in prolonged stability in some patients. Further development of this regimen is warranted. © 2020 S. https://www.selleckchem.com/products/cx-5461.html Karger AG, Basel.BACKGROUND The NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) or bare-metal stent (BMS) with 5-year follow-up. No difference was found in the composite primary outcome of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularizations, which were reduced by DES. We report the occurrence of target lesion revascularization (TLR) in time and across demographic and clinical subgroups in patients with lesions in native coronary arteries (n = 8,782). RESULTS Clinically driven TLR was performed on 488 (5.6%) of the 8,782 patients during 5 years of follow-up. Male gender, older age, visible thrombus in the lesion, and larger stent diameter were associated with less TLR; multivessel disease and longer stents were associated with a higher risk of TLR. There was a substantial and highly significant reduction of the risk of any TLR after 5 years in the DES group (hazard ratio [HR] 0.