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Benson M.,Nuffield Orthopaedic Center | Boehler N.,Nuffield Orthopaedic Center | Szendroi M.,Nuffield Orthopaedic Center | Szendroi M.,Semmelweiss University | And 3 more authors.
Bone and Joint Journal | Year: 2014

This paper offers a summary of the ethical guide for the European orthopaedic community; the full report will be published in the EFORT Journal. ©2014 The British Editorial Society of Bone & Joint Surgery.

Boshier P.R.,Imperial College London | Mistry V.,Imperial College London | Cushnir J.R.,Imperial College London | Kon O.M.,Imperial College London | And 5 more authors.
Journal of Surgical Research | Year: 2015

Background Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury.Methods Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls.Results Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls.Conclusions Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia. © 2015 Elsevier Inc. All rights reserved.

Remenyi A.,Obuda University | Szenasi S.,Obuda University | Bandi I.,Obuda University | Vamossy Z.,Obuda University | And 4 more authors.
LINDI 2011 - 3rd IEEE International Symposium on Logistics and Industrial Informatics, Proceedings | Year: 2011

The main aim of this work is to show, how GPGPUs can facilitate certain type of image processing methods. The software used in this paper is used to detect special tissue part, the nuclei on (HE - hematoxilin eosin) stained colon tissue sample images. Since pathologists are working with large number of high resolution images - thus require significant storage space -, one feasible way to achieve reasonable processing time is the usage of GPGPUs. The CUDA software development kit was used to develop processing algorithms to NVIDIA type GPUs. Our work focuses on how to achieve better performance with coalesced global memory access when working with three-channel RGB tissue images, and how to use the on-die shared memory efficiently. © 2011 IEEE.

Kristensen S.L.,University of Glasgow | Kristensen S.L.,Copenhagen University | Preiss D.,University of Glasgow | Jhund P.S.,University of Glasgow | And 17 more authors.
Circulation: Heart Failure | Year: 2016

The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results-We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17-1.64); P<0.001 and 1.64 (1.43-1.87); P<0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions-In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. © 2015 American Heart Association, Inc.

Knowles H.J.,University of Oxford | Knowles H.J.,Nuffield Orthopaedic Center | Moskovsky L.,Semmelweiss University | Thompson M.S.,University of Oxford | And 9 more authors.
Virchows Archiv | Year: 2012

Multinucleated cells termed chondroclasts have been observed on the deep surface of resorbed hyaline cartilage but the relationship of these cells to macrophages and osteoclasts and their role in rheumatoid arthritis (RA) and other arthritic conditions is uncertain. Multinucleated cells in RA and other arthritic conditions showing evidence of cartilage resorption were characterised immunohistochemically for expression of macrophage/osteoclast markers. Mature human osteoclasts formed from circulating monocytes and tissue macrophages were cultured for up to 4 days on slices of human cartilage and glycosaminoglycan (GAG) release was measured. Multinucleated cells resorbing unmineralised cartilage were seen in osteoarthritis, RA, septic arthritis, avascular necrosis and in four cases of giant cell tumour of bone that had extended through the subchondral bone plate. Chondroclasts expressed an osteoclast-like phenotype (TRAP+, cathepsin K+, MMP9+, CD14-, HLADR-, CD45+, CD51+ and CD68+). Both macrophages and osteoclasts cultured on cartilage released GAG. These findings indicate that chondroclasts have an osteoclast-like phenotype and that mature human osteoclasts are capable of cartilage matrix resorption. Resorption of unmineralised subchondral cartilage by chondroclasts and macrophages can be a feature of joint destruction in inflammatory and non-inflammatory arthropathies as well as inflammatory and neoplastic subchondral bone lesions. © Springer-Verlag 2012.

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