Activated protein C increases sensitivity to vasoconstriction in rabbit Escherichia coli endotoxin-induced shock

INTRODUCTION: The aim of this study was to investigate the effects of activated protein C (aPC) on vascular function, endothelial injury, and haemostasis in a rabbit endotoxin-induced shock model. METHOD: This study included 22 male New Zealand rabbits weighing 2.5 to 3 kg each. In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors and monocyte tissue factor (TF) expression were performed 5 days (D5) after onset of endotoxic shock (initiated by 0.5 mg/kg intravenous bolus of Escherichia coli lipopolysaccharide (LPS)) with or without treatment with aPC injected as an intravenous 2 mg/kg bolus 1 hour after LPS (LPS+aPC group and LPS group, respectively). RESULTS: LPS decreased the sensitivity to phenylephrine (PE) in aortic rings without endothelium (E-) when compared to E- rings from the control group (p < 0.05). This was abolished by N(G)-nitro-L-arginine methyl ester and not observed in E- rings from aPC-treated rabbits. Although aPC failed to decrease monocyte TF expression in endotoxinic animals at D5, aPC treatment restored the endothelium-dependent sensitivity in response to PE (2.0 ± 0.2 μM in rings with endothelium (E+) versus 1.0 ± 0.2 μM in E- rings (p < 0.05) in the LPS+aPC group versus 2.4 ± 0.3 μM in E+ rings versus 2.2 ± 0.2 μM in E- rings (p value not significant), in the LPS group). Endotoxin-induced de-endothelialisation was reduced by aPC at D5 (28.5 ± 2.3% in the LPS+aPC group versus 40.4 ± 2.4% in the LPS group, p < 0.05). CONCLUSION: These data indicate that aPC increased the sensitivity to a vasoconstrictor agent (PE) associated with restoration of endothelial modulation, and protected against endothelial histological injury in endotoxin-induced shock. It failed to inhibit TF expression at D5 after LPS injection

Endotoxin-induced myocardial dysfunction in senescent rats

INTRODUCTION: Aging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction. METHODS: Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca(2+ )sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO(2)) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated. RESULTS: LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 ± 4 vs 53 ± 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 ± 7 vs 100 ± 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca(2+ )sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO(2 )were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals. CONCLUSION: Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca(2+ )myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca(2+)-sensitizing agents may not be as effective in aged subjects as in younger subjects

Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

International audienc

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO(2):FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 μg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 μg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 μg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program

Le cadre théorique du concept de web triangulation (une analyse par théorisation ancrée du dialogue médecin-patient lié à l'Internet durant la consultation)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Bilan d éducation (pratiques des médecins généralistes du Nord-Pas-de-Calais)

Contexte : La HAS et l INPES ont publié un guide méthodologique qui décrit la démarche d ETP dont la première étape est le diagnostic éducatif. Malgré ces travaux, la place et le rôle des médecins généralistes restent flous. La plupart des médecins généralistes pratiquent une activité d ETP de façon plus ou moins formalisée. Les recommandations établies par la has concernant la démarche éducative semblent difficiles à appliquer en pratique de médecine générale ambulatoire. Question : Comment est abordé le diagnostic éducatif du patient en médecine générale dans la région Nord-Pas-de-Calais ? Méthode : Une étude qualitative par entretiens semi-dirigés a été menée auprès de médecins généralistes impliqués en ETP. Les entretiens ont été rendus anonymes, enregistrés et intégralement retranscrits puis ont fait l objet d une double analyse. Le recrutement s est poursuivi jusqu à la saturation des informations. L analyse a été effectuée à l aide du logiciel de recherche qualitative N-Vivo. Résultats : 10 entretiens ont été réalisés. L étude a montré que la plupart des médecins généralistes interrogés ne faisaient pas de consultation dédiée au diagnostic éducatif. Celui-ci est le plus souvent fait au cours de consultations de suivi. La consultation dédiée est en général vue comme inadaptée du fait du manque d outils disponibles, du manque de temps du médecin et du patient, du manque de motivation du patient et aussi du fait que le médecin connaît en général depuis longtemps les patients qu il suit. Les médecins interrogés ne disposent pas de méthode bien précise pour établir le diagnostic éducatif. Souvent les informations sont recueillies petit à petit. La réévaluation est en général continue, au cours des consultations de suivi et ne porte en général que sur un axe à la fois. Conclusion : La réalisation du bilan d éducation telle qu elle est décrite par la Haute Autorité de Santé semble compliquée à mettre en place par les médecins généralistes du fait de la spécificité de leur pratique, et d une relation médecin-malade différente de celle du milieu hospitalier.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Evaluation de la satisfaction des acteurs, du respect des objectifs et de l'intérêt pédagogique des unités pédagogiques locales instaurées à la faculté de Médecine de Lille de mai à octobre 2004

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

RETENTISSEMENT DES GOITRES SUR L'INTUBATION TRACHEALE

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Influence de l image de la médecine générale sur le désir de choix de la spécialité (enquête réalisée auprès de 825 étudiants hospitaliers lillois)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF