BackgroundPleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad-spectrum antibiotics, since reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical trial assessing the safety and significance of ultrasound (US)-guided pleural biopsy culture to increase the microbiological yield.Methods20 patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US-guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. In an exploratory sub-study, the 16S rRNA technique was applied on pleural biopsy samples, to investigate its’ utility on increasing speed and accuracy versus standard microbiological diagnosis. This trials is registered with , number NCT02608814FindingsUS-guided were safe with no adverse events observed in this study. Pleural biopsies increased microbiological yield by 30% in addition to pleural fluid and blood samples (combined diagnostic sensitivity 55%). US characteristics at baseline were not statistically associated with survival, fluid volume drainage, radiological improvement or need for surgery. The 16S rRNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89·5%).ConclusionOur findings demonstrate safety of conducting US guided biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis. qPCR primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.FundingOxfordshire Health Services Research CommitteeAbstract 24 Figure 1(A)% increase on positive culture samples in patients with pleural infection, (B) Results of pleural biopsy culture, and (C) Gram stain of acute inflammatory exudate in a pleural biopsy showing small colonies of Gram positive cocci.
BackgroundCarcinogen-inflicted human cancers, including lung tumours harbour thousands of mutations per genome, most of which are unknown (Garraway, LA et al, Cell 2013;153:17–37).AimTo develop a faithful mouse model of human tobacco carcinogen-induced lung adenocarcinoma suitable for the identification of novel oncogenic genes and pathways.MethodsWe repeatedly managed to obtain several murine lung adenocarcinoma cell lines (MLA) by chronically exposing various mouse strains to different tobacco carcinogens. MLA were characterised for cancer stemness and oncogenes, as well as global gene expression.ResultsTo date, 12 MLA cell lines have been derived from Wt and transgenic mice on the FVB, Balb/c, and C57BL/6 strains by means of urethane or diethylnitrosamine exposure. All MLA were immortal, phenotypically stable, and indefinitely passaged in vitro over a period of over 18 months and/or 60 passages. In addition, all cell lines were oncogenic, transplantable, metastatic, and uniformly lethal in vivo. Interestingly, MLA displayed Kras mutations in codon 61, mono- or bi-allelic Trp53 loss, and expression of lung cancer stemness factors Itgb3 and Lgr6, in amazing similarity to human lung cancers. Microarray revealed that all MLA cell lines heavily overexpressed Prl2c2, encoding proliferin, in comparison to the native lungs. Prl2c2 silencing diminished MLA proliferation and stemness, to a degree comparable with Itgb3 interference.ConclusionsMLA are faithful models of human lung adenocarcinoma that led to the discovery of Prl2c2 as a candidate lung tumour promoter.FundingEuropean Research Council Starting Independent Investigator Grant #260524. Respire 2 European Respiratory Society Fellowship, European Respiratory Society Short Term Research Fellowship.
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