042: Real life dual antiplatelet therapy after NSTE-ACS in a Tunisian population: is there a need for 12 months of treatment?

AimEven if the recommended duration for dual antiplatelet therapy (DAT) after non ST elevation acute coronary syndromes (NSTE-ACS) is 12 months, evidence concerning the benefit of clopidogrel adjunction especially beyond 3 months remains poor. The aim of the study was to assess the effective clopidogrel intake and the incidence of a composite endpoint including all causes death and non fatal myocardial infarction in a Tunisian population after NSTE-ACS.MethodsWe included patients admitted for NSTE-ACS in our department between January 2010 and August 2011 for whom long term evaluation was possible. In-hospital deaths were excluded (including post operative deaths). By telephone follow up, we evaluated the effective DAT duration and the occurrence of all causes death and non-fatal myocardial infarction.ResultsOne hundred thirty patients were included. Mean (SD) follow up was 261 (99) days. DAT was effectively observed during 94(103 days (extremes ranging from 0 to 360 days). Angioplasty was performed in 51.5%, coronary artery bypass graft in 8.4% and medical therapy was considered in 40.1%. In 35 (26.9%) patients, aspirin was the only antiplatelet therapy taken after discharge although DAT was prescribed; 46.9% of the patients took the DAT for more than 3 months, and 23.1% for more than 6 months. The composite endpoint occurred in 6 (4.6%) patients: 2 deaths (both of cardiac causes) and 4 myocardial infarctions. Three of them were under DAT, and the 3 others remained event free during 7, 240 and 270 days after clopidogrel withdrawal. These findings suggest that DAT does not protect against death or myocardial infarction. The rebound phenomenon after clopidogrel withdrawal isn’t patent in our population.ConclusionIn the Tunisian context, DAT observance is poor after NSTE-ACS. Death and non fatal myocardial infarction don’t seem to be reduced by DAT and the rebound phenomenon after clopidogrel withdrawal isn’t patent. This may be in part attributed to the small sample of population and the predominantly low risk (as assessed by TIMI risk score), but larger studies are needed to strengthen the evidence for DAT after NSTE-ACS

Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties of Acacia Honey from the Hail Region: The in vitro and in silico Investigation

In consideration of the emergence of novel drug-resistant microbial strains and the increase in the incidences of various cancers throughout the world, honey could be utilized as a great alternative source of potent bioactive compounds. In this context, this study pioneers in reporting the phytochemical profiling and the antimicrobial, antioxidant, and anticancer properties of Acacia honey (AH) from the Hail region of Saudi Arabia, assessed using in vitro and molecular docking approaches. The phytochemical profiling based on high-resolution liquid chromatography-mass spectrometry (HR-LCMS) revealed eight compounds and three small peptide-like proteins as the constituents. The honey samples exhibited promising antioxidant activities (DPPH-IC50 = 0.670 mg/mL; ABTS-IC50 = 1.056 mg/mL; β-carotene-IC50 > 5 mg/mL). In the well-diffusion assay, a high mean growth inhibition zone (mGIZ) was observed against Staphylococcus aureus (48.33 ± 1.53 mm), Escherichia coli ATCC 10536 (38.33 ± 1.53 mm), and Staphylococcus epidermidis ATCC 12228 (39.33 ± 1.15 mm). The microdilution assay revealed that low concentrations of AH could inhibit the growth of almost all the evaluated bacterial and fungal strains, with the minimal bactericidal concentration values (MBCs) ranging from 75 mg/mL to 300 mg/mL. On the contrary, high AH concentrations were required to kill the tested microorganisms, with the minimal bactericidal concentration values (MBCs) ranging from approximately 300 mg/mL to over 600 mg/mL and the minimal fungicidal concentration values (MFCs) of approximately 600 mg/mL. The AH exhibited effective anticancer activity in a dose-dependent manner against breast (MCF-7), colon (HCT-116), and lung (A549) cancer cell lines, with the corresponding IC50 values of 5.053 μg/mL, 5.382 μg/mL, and 6.728 μg/mL, respectively. The in silico investigation revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of AH are thermodynamically feasible, particularly those of the tripeptides (Asp-Trp-His and Trp-Arg-Ala) and aminocyclitol glycoside. The overall results highlighted the potential of AH as a source of bioactive compounds with significant antimicrobial, antioxidant, and anticancer activities, which could imply further pharmacological applications of AH

Hepatobiliary manifestations following two-stages elective laparoscopic restorative proctocolectomy for patients with ulcerative colitis: A prospective observational study

BACKGROUNDHepatobiliary manifestations occur in ulcerative colitis (UC) patients. The effect of laparoscopic restorative proctocolectomy (LRP) with ileal pouch anal anastomosis (IPAA) on hepatobiliary manifestations is debated.AIMTo evaluate hepatobiliary changes after two-stages elective laparoscopic restorative proctocolectomy for patients with UC.METHODSBetween June 2013 and June 2018, 167 patients with hepatobiliary symptoms underwent two-stage elective LRP for UC in a prospective observational study. Patients with UC and having at least one hepatobiliary manifestation who underwent LRP with IPAA were included in the study. The patients were followed up for four years to assess the outcomes of hepatobiliary manifestations.RESULTSThe patients' mean age was 36 +/- 8 years, and males predominated (67.1%). The most common hepatobiliary diagnostic method was liver biopsy (85.6%), followed by Magnetic resonance cholangiopancreatography (63.5%), Antineutrophil cytoplasmic antibodies (62.5%), abdominal ultrasonography (35.9%), and Endoscopic retrograde cholangiopancreatography (6%). The most common hepatobiliary symptom was Primary sclerosing cholangitis (PSC) (62.3%), followed by fatty liver (16.8%) and gallbladder stone (10.2%). 66.4% of patients showed a stable course after surgery. Progressive or regressive courses occurred in 16.8% of each. Mortality was 6%, and recurrence or progression of symptoms required surgery for 15%. Most PSC patients (87.5%) had a stable course, and only 12.5% became worse. Two-thirds (64.3%) of fatty liver patients showed a regressive course, while one-third (35.7%) showed a stable course. Survival rates were 98.8%, 97%, 95.8%, and 94% at 12 mo, 24 mo, 36 mo, and at the end of the follow-up.CONCLUSIONIn patients with UC who had LRP, there is a positive impact on hepatobiliary disease. It caused an improvement in PSC and fatty liver disease. The most prevalent unchanged course was PSC, while the most common improvement was fatty liver disease

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

La métaphore conceptuelle en métadiscours

Inscrire d’emblée cet article dans le cadre du cognitivisme relève du pari sur le conceptuel.Il s’agit en effet d’une approche qui s’offre à la fois comme approfondissement et comme réévaluation : elle est approfondissement parce qu’elle pointe le sujet discoureur dans sa conversion en sujet pensant; elle est également réévaluation parce qu’elle autorise aux signes de se signifier autrement. Comme concrétisation de cet esprit innovateur dont fait montre cette approche, nous proposerons de saisir le métadiscours comme support d’étude de la métaphore conceptuelle, et ce à travers deux principaux ouvrages que nous prenons commeassez présentatifs de l’ensemble de l’«esthétique» métalinguistique; il s’agit donc deGrammaire méthodologique du français1 et Dictionnaire de la linguistique2. Dans un premier moment, nous serons fort tenté par le volet définitoire où seront exposésles principaux concepts relatifs à la métaphore conceptuelle. Dans un deuxième moment, nousnous appliquerons à examiner la notion de spatialisation qui préside à un nombre importantde concepts métadisursifs. Nous comptons démontrer, dans la dernière partie, en quoi l’esprithumain s’assigne sa propre expérience corporelle, et par là même ontologique, comme sous-bassement de la métaphore (méta)discursiv

Constrained Uncertain System Stabilization with Enlargement of Invariant Sets

An enhanced method able to perform accurate stability of constrained uncertain systems is presented. The main objective of this method is to compute a sequence of feedback control laws which stabilizes the closed-loop system. The proposed approach is based on robust model predictive control (RMPC) and enhanced maximized sets algorithm (EMSA), which are applied to improve the performance of the closed-loop system and achieve less conservative results. In fact, the proposed approach is split into two parts. The first is a method of enhanced maximized ellipsoidal invariant sets (EMES) based on a semidefinite programming problem. The second is an enhanced maximized polyhedral set (EMPS) which consists of appending new vertices to their convex hull to minimize the distance between each new vertex and the polyhedral set vertices to ensure state constraints. Simulation results on two examples, an uncertain nonisothermal CSTR and an angular positioning system, demonstrate the effectiveness of the proposed methodology when compared to other works related to a similar subject. According to the performance evaluation, we recorded higher feedback gain provided by smallest maximized invariant sets compared to recently studied methods, which shows the best region of stability. Therefore, the proposed algorithm can achieve less conservative results

Suivi et control de l'endommagement des matériaux composites à renfort carbone et résines nanochargées par la méthode piézorésistive

International audienceIn this work, electrical resistance change method is used for Carbon Fiber Reinforced Thermoplastic Polymers (CFRTP) damage monitoring. The electrical resistance couldbe an interesting complementary to existing/classical damage monitoring methods. It is extremely attributed to electrical conductivity of composite material and it appears that enhancing the conductivity of materials, by the use of conductive nanofillers in our case, improves their sensitivity to mechanical loading. CFRTP with different nanofillers types and concentrations were manufactured and tested in tensile loading. Concentration of 0 and 8wt % of carbon black (CB) and 2.5wt % of carbon nanotubes (CNT) were used with Polyamide 6 sheets as matrix. Nanofillers weakening effect was discussed according to their concentrations and types. The acoustic emission (AE), digital image correlation (DIC) and in situ microscopy were also recorded during testing. A correlation between all these signals and the evolution of the electrical resistance of the composites during the tensile loading was performed. It was found that CB enhances sensitivity of CFRTP to damage detection, especially delamination. For the CNT, results are less promising. A discussion is held about the nanofillers concentration influence.Cette étude consiste à déployer la méthode piézorésistive le suivi de l’endommagement pour des composites à matrice thermoplastique nanochargée. La résistance électrique pourrait constituer un complément intéressant aux méthodes de contrôle d’endommagements existantes/classiques. Cela passe par l’augmentation de la conductivité électrique des matériaux composites et il apparait que cette amélioration, par l’utilisation de nanocharges conductrices, améliore leur sensibilité aux endommagements. Des composites avec différents types et concentrations de nanocharges ont été fabriqués et testés en traction. Des concentrations de 8% en poids de noir de carbone (CB) et 2,5% en poids de nanotubes de carbone (CNT) ont été dispersées dans du polyamide 6 comme matrice. L’effet fragilisant des nanocharges a été examiné en fonction de leurs concentrations et de leurs types. L’émission acoustique (AE), la corrélation d'images numériques (DIC) et la microscopie in situ ont également été enregistrés au cours des tests. Une corrélation entre tous ces signaux et l'évolution de la résistance électrique des composites lors du chargement en traction a été réalisée. Il a été constaté que le CB augmente la sensibilité des CMO à la détection des dommages, en particulier au délaminage. Pour le CNT, les résultats sont moins prometteurs