Genomic landscape of lung adenocarcinoma in East Asians

Lung cancer is the world’s leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts

An underused opportunity to introduce ACE inhibitors and influence prognosis: observational study of patients undergoing aortic surgery

OBJECTIVE: To asses whether Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are underused in patients with aortic disease due to concerns regarding flow limiting (>70%) renal artery stenosis (RAS). DESIGN: A prospective analysis of patients admitted for aortic surgery was performed (January-July 2009). Co-morbidity, ACEI/ARB use and renal function were recorded. Computerised tomography (CT) angiograms were reviewed by a single blinded radiologist for the presence and severity of RAS. SETTING: St Mary's Hospital, Vascular Unit, Imperial College Healthcare NHS Trust, London, UK. PARTICIPANTS: 75 randomly selected patients admitted to our vascular unit including elective and emergency admissions. MAIN OUTCOME MEASURES: Indications for ACEI therapy were identified as determined by the National Institute of Health and Clinical Excellence (NICE) guidance. The ratio of the measurement distal to the stenosis and at the area of maximal stenosis on CT angiography were used to calculate the percentage RAS. RESULTS: 60 patients were identified (15 patients excluded due to previously modified renal vessels). The median age was 73 [interquartile range 68, 77]. Their underlying aortic disease included 52 (87%) aortic aneurysm, 6 (10%) with aortic dissection, 1 (1.7%) patient with occlusive disease and 1 (1.7%) patient with mycotic disease. Overall, 56/60 (93%) patients had at least one indication for ACEI therapy. 33/60 (55%) of patients were already receiving ACEI. CT angiogram examination demonstrated 17/60 (28%) patients have RAS of some degree, of which only 9/60 (15%) have flow limiting RAS. CONCLUSION: A large proportion of aortic patients do not receive ACEI/ARB therapy despite definite indications and a low prevalence of flow-limiting RAS is low. After the exclusion of RAS at angiography, careful introduction of ACEI therapy with appropriate monitoring could be considered for many more patients

A national point-prevalence survey of the practice of sedation, analgesia, neuromuscular blockade and delirium assessment in adult intensive care units in Singapore

Critical Care and Shock134122-13