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Davies K.A.,University of Leeds | Longshaw C.M.,Astellas Pharma Europe | Davis G.L.,University of Leeds | Bouza E.,Hospital General Universitario Gregorio Maranon | And 18 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe. Methods: We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012-13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched. Findings: During the study period, participating hospitals reported a mean of 65.8 tests (country range 4.6-223.3) for C difficile infection per 10 000 patient-bed days and a mean of 7.0 cases (country range 0.7-28.7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011-12 to 205 (48%) of 428 in 2012-13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory) were not diagnosed by participating hospitals because of an absence of clinical suspicion, equating to about 74 missed diagnoses per day. Interpretation: A wide variety of testing strategies for C difficile infection are used across Europe. Absence of clinical suspicion and suboptimum laboratory diagnostic methods mean that an estimated 40 000 inpatients with C difficile infection are potentially undiagnosed every year in 482 European hospitals. Funding: Astellas Pharmaceuticals Europe. © 2014 Elsevier Ltd. Source


Rabolli V.,Catholic University of Louvain | Wallemme L.,Catholic University of Louvain | Lo Re S.,Catholic University of Louvain | Uwambayinema F.,Catholic University of Louvain | And 9 more authors.
Journal of Biological Chemistry | Year: 2014

Rapid changes in cell volume characterize macrophage activation, but the role of water channels in inflammation remains unclear. We show here that, in vitro, aquaporin (AQP) blockade or deficiency results in reduced IL-1β release by macrophages activated with a variety of NLRP3 activators. Inhibition of AQP specifically during the regulatory volume decrease process is sufficient to limit IL-1β release by macrophages through the NLRP3 inflammasome axis. The immune-related activity of AQP was confirmed in vivo in a model of acute lung inflammation induced by crystals. AQP1 deficiency is associated with a marked reduction of both lung IL-1β release and neutrophilic inflammation. We conclude that AQP-mediated water transport in macrophages constitutes a general danger signal required for NLRP3-related inflammation. Our findings reveal a new function of AQP in the inflammatory process and suggest a novel therapeutic target for anti-inflammatory therapy. ©2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Rueda-Rincon N.,Catholic University of Leuven | Bloch K.,Catholic University of Leuven | Derua R.,Catholic University of Leuven | Vyas R.,Catholic University of Leuven | And 11 more authors.
Oncotarget | Year: 2015

The p53 tumor suppressor is the central component of a complex network of signaling pathways that protect organisms against the propagation of cells carrying oncogenic mutations. Here we report a previously unrecognized role of p53 in membrane phospholipids composition. By repressing the expression of stearoyl-CoA desaturase 1, SCD, the enzyme that converts saturated to mono-unsaturated fatty acids, p53 causes a shift in the content of phospholipids with mono-unsaturated acyl chains towards more saturated phospholipid species, particularly of the phosphatidylinositol headgroup class. This shift affects levels of phosphatidylinositol phosphates, attenuates the oncogenic AKT pathway, and contributes to the p53- mediated control of cell survival. These findings expand the p53 network to phospholipid metabolism and uncover a new molecular pathway connecting p53 to AKT signaling. Source


Binda M.M.,Institute Of Recherche Experimentale Et Clinique Irec
Archives of Gynecology and Obstetrics | Year: 2015

Purpose: The peritoneum is the serous membrane that covers the abdominal cavity and most of the intra-abdominal organs. It is a very delicate layer highly susceptible to damage and it is not designed to cope with variable conditions such as the dry and cold carbon dioxide (CO2) during laparoscopic surgery. The aim of this review was to evaluate the effects caused by insufflating dry and cold gas into the abdominal cavity after laparoscopic surgery. Methods: A literature search using the Pubmed was carried out. Articles identified focused on the key issues of laparoscopy, peritoneum, morphology, pneumoperitoneum, humidity, body temperature, pain, recovery time, post-operative adhesions and lens fogging. Results: Insufflating dry and cold CO2 into the abdomen causes peritoneal damage, post-operative pain, hypothermia and post-operative adhesions. Using humidified and warm gas prevents pain after surgery. With regard to hypothermia due to desiccation, it can be fully prevented using humidified and warm gas. Results relating to the patient recovery are still controversial. Conclusions: The use of humidified and warm insufflation gas offers a significant clinical benefit to the patient, creating a more physiologic peritoneal environment and reducing the post-operative pain and hypothermia. In animal models, although humidified and warm gas reduces post-operative adhesions, humidified gas at 32 °C reduced them even more. It is clear that humidified gas should be used during laparoscopic surgery; however, a question remains unanswered: to achieve even greater clinical benefit to the patient, at what temperature should the humidified gas be when insufflated into the abdomen? More clinical trials should be performed to resolve this query. © 2015, The Author(s). Source


Beauloye C.,Cliniques universitaires Saint Luc | Beauloye C.,Institute Of Recherche Experimentale Et Clinique Irec | Vrolix M.,Ziekenhuis Oost Limburg | Claeys M.J.,University of Antwerp | And 3 more authors.
Acta Cardiologica | Year: 2016

Objectives This sub-analysis of the EPICOR study describes pre-hospital care (PHC) patterns in Belgium, Luxembourg (Belux) and Western European (WEU) countries (Finland, Norway, Denmark, the Netherlands, UK, Belgium, Luxembourg, Spain, France, Italy, Greece and Germany). Methods and results EPICOR (NCT01171404) is a multinational, observational study comprising patients with acute coronary syndrome hospitalized within 24 h of symptoms onset, diagnosed with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or unstable angina (UA). Of the 325 WEU centres, 37 were in Belgium and 1 in Luxembourg. PHC was defined as pre-hospital ECG and/or pre-hospital medication (PHM). 504 Belux and 6,119 WEU patients were enrolled. Of the WEU patients 51.5% received PHC and 28.1% PHM, compared to 27.6% and 11.3% of the Belux patients. These differences were observed in both STEMI and UA/NSTEMI patients. In Belux, the most frequent PHM was acetylsalicylic acid (53 patients); only 1 patient received thrombolytics. The median time from symptoms onset to ECG was longer for Belux (2.8 h) than for WEU patients (2.4 h). PHC shortened this time by almost 1.5h. Belux patients with PHC had a shorter median time between symptoms onset and first medical attention (FMA) than WEU patients (1.0 h vs 1.3 h). Only 34.7% of Belux patients with pre-hospital ECGandwith timefrom FMA to ECG available had ECG within 10minutesofFMA,as recommended by the European Society of Cardiology. Conclusions In Belux, diagnostic ECG is delayed compared to WEU, despite the short time to FMA. Few patients undergo ECG within the recommended period, indicating room for improvement. © 2016, Acta Cardiologica. All rights reserved. Source

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