Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Overlap in the clinical features of pneumonia and malaria in African children

Abstract: Pneumonia and malaria are common causes of childhood morbidity and mortality in many developing countries and simple guidelines have been proposed to facilitate their diagnosis by relatively unskilled health workers. We have studied children in The Gambia attending out-patient and under-five clinics with clinically suspected pneumonia (cough or difficulty in breathing and a raised respiratory rate) during periods of high or low malaria transmission. During a period of high malaria transmission, 33% of these children had radiological evidence of pneumonia (with or without malaria parasitaemia) compared to 38% who had malaria parasitaemia, no radiological evidence of pneumonia and no other obvious cause of fever. Corresponding figures during a period of low malaria transmission were 48% and 6% respectively. The clinical overlap between pneumonia and malaria has important implications for case management strategies and evaluation of disease-specific interventions in regions in which both pneumonia and malaria are prevalent.

High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial

Abstract: FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1 -amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy. Significance: Robust single-agent response to FGFR inhibition is seen only in high-level FGFR -amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo , and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. Cancer Discov; 6(8); 838–51. ©2016 AACR. This article is highlighted in the In This Issue feature, [p. 803][1] [1]: /lookup/volpage/6/803?iss=8

The measured effect of stopping smoking on intermittent claudication

Abstract: One hundred and twenty-four limbs in patients suffering from intermittent claudication were studied over 10 months. Changes in ankle pressure and treadmill exercise tolerance over the period were compared between two groups, one of patients who continued to smoke (group 1) and the other of those who gave up (group 2). Resting ankle systolic pressure fell in smokers' limbs by a mean of 10·2 mmHg (t = 3·56, P < 0·001), and rose in those patients who stopped smoking by a mean 8·7 mmHg (P - n.s.). Ankle pressures after exercise and maximum treadmill walking distance did not change in smokers but significantly improved in past smokers. Stopping cigarette smoking increased the chance of improvement in ankle pressure and exercise tolerance in intermittent claudication.

Subintimal angioplasty of femoropopliteal artery occlusions: The long-term results

Abstract: The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions 20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.

Linear and nonlinear analysis of human dynamic cerebral autoregulation

Abstract: The linear dynamic relationship between systemic arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) was studied by time- and frequency-domain analysis methods. A nonlinear moving...