The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT -PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (Po0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival. Methods: An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. Analysis was conducted according to a prespecified protocol (NCT: 03979222). Data are presented as median [inter-quartile range, IQR]. Results: A total of 1205 patients were supported with ECMO during the study period; the majority (n¼1150; 95%) had venovenous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n¼887). Survivors had a lower median age (43 yr [32e52]), compared with non-survivors (49 y [39e60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival: survivors had a median SaO 2 of 90% (84e93%; median PaO 2 /FiO 2 , 9.4 kPa [7.7e12.6]), compared with non-survivors (SaO 2 88% [80e92%]; PaO 2 /FiO 2 ratio: 8.5 kPa [7.1e11.5]). Patients requiring ECMO because of asthma were more likely to survive (95% survival rate (95% CI, 91e99%), compared with a survival of 71% (95% CI, 69e74%) in patients with respiratory failure attributable to other diagnoses. Conclusion: A national ECMO service can achieve good short-term outcomes for patients with undifferentiated respiratory failure refractory to conventional management. Clinical trial registration: NCT 03979222.

Objectives: According to National Health Service England (NHSE) specialist respiratory commissioning specification for complex home ventilation, patients with weaning failure should be referred to a specialist centre. However, there are limited data reporting the clinical outcomes from such centres.