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Aims Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) Methods and results In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P Conclusion In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H

International audience; Background: The accuracy of surgical scores in predicting in-hospital mortality for nonsurgically treated patients with infective endocarditis (IE) has not yet been explored.Methods: Patients with definite IE who did not undergo valve surgery were selected from the database of seven French administrative areas (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse [AEPEI] Registry, 2008). The patients were scored using (a) six systems specifically devised to predict in-hospital mortality after surgery for IE, (b) three commonly used risk scores for heart surgery, and (c) a risk score for predicting six-month mortality in IE after either surgery or medical therapy. Calibration (Hosmer-Lemeshow test) and discriminatory power (receiver operating characteristic [ROC] analysis) were assessed for each score. Areas under ROC curves were compared one-to-one (Hanley-McNeil method).Results: A total of 192 patients (mean age, 65.2±15.2 years) were considered for analysis. There were 38 (19.8%) in-hospital deaths. Age >70 years (p=0.001), Staphylococcus aureus as causal agent (p=0.05), and severe sepsis (p=0.027) were independent predictors of in-hospital mortality. Despite many differences in the number and type of variables, all but two of the investigated scores showed good calibration (p>0.66). However, discriminatory power was satisfactory (area under ROC curve >0.70) only for three of the scores specific for IE and two of the scores used to predict mortality after cardiac surgery.Conclusions: Among the 10 surgical scores evaluated in this study, five could be adopted to predict in-hospital mortality even for IE patients receiving medical treatment only.

Health-care workers are crucial to any health-care system. During the ongoing COVID-19 pandemic, health-care workers are at a substantially increased risk of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and could come to considerable harm as a result. Depending on the phase of the pandemic, patients with COVID-19 might not be the main source of SARS-CoV-2 infection and health-care workers could be exposed to atypical patients, infected family members, contacts, and colleagues, or live in communities of active transmission. Clear strategies to support and appropriately manage exposed and infected health-care workers are essential to ensure effective staff management and to engender trust in the workplace. These management strategies should focus on risk stratification, suitable clinical monitoring, low-threshold access to diagnostics, and decision making about removal from and return to work. Policy makers need to support health-care facilities in interpreting guidance during a pandemic that will probably be characterised by fluctuating local incidence of SARS-CoV-2 to mitigate the impact of this pandemic on their workforce.

BackgroundMolecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. Despite massive worldwide efforts, the high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the performances of a new ELISA microplate assay quantifying SARS-CoV-2 nucleocapsid antigen (N-antigen) in serum or plasma.MethodsThe specificity of the assay, determined on 63 non-COVID patients, was 98.4% (95% confidence interval [CI], 85.3 to 100). Performances were determined on 227 serum samples from 165 patients with RT-PCR confirmed SARS-CoV-2 infection included in the French COVID and CoV-CONTACT cohorts.FindingsSensitivity was 132/142, 93.0% (95% CI, 84.7 to 100), within the first two weeks after symptoms onset. A subset of 73 COVID-19 patients had a serum collected within 24 hours following or preceding a positive nasopharyngeal swab. Among patients with high nasopharyngeal viral loads, Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among patients with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia. The lower respiratory tract was explored for 6/8 patients, showing positive PCR in 5 cases.InterpretationThis is the first demonstration of the N-antigen antigenemia during COVID-19. Its detection presented a robust sensitivity, especially within the first 14 days after symptoms onset and high nasopharyngeal viral loads. These findings have to be confirmed with higher representation of outpatients. This approach could provide a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.

International audience; Purpose - To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV). Methods - We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012-2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza. Results - Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1-2.0], P = 0.008), and diabetes (OR 0.5 [0.4-0.8], P = 0.01) were associated with NIRV detection. Conclusions - NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

IntroductionLeft-sided infective endocarditis (IE) is a serious infection with a heavy burden for patients and healthcare system. Oral switch after initial intravenous antibiotic therapy may reduce costs and improve patients’ discomfort without increasing unfavourable outcomes. We describe the methodology of two simultaneously conducted open-label randomised trials aiming to assess non-inferiority of oral switch as compared with entirely intravenous antibiotic therapy for the treatment of left-sided IE.Methods and analysisTwo simultaneous multicentre open-label prospective randomised trials assessing non-inferiority of oral switch during antibiotic treatment as compared with entirely intravenous therapy in patients with left-sided IE are ongoing. One trial is dedicated to left-sided IE caused by multisusceptible staphylococci (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques (RODEO)-1) and the other is dedicated to left-sided IE caused by susceptible streptococci or enterococci (RODEO-2). It is planned to randomise 324 patients in each trial after an initial course of at least 10 days of intravenous antibiotic therapy either to continue intravenous antibiotic therapy or to switch to oral antibiotic therapy. The primary outcome is treatment failure within 3 months after the end of antibiotic treatment, a composite outcome defined by all-cause death and/or symptomatic embolic events and/or unplanned valvular surgery and/or microbiological relapse (with the primary pathogen). Secondary outcomes include patient quality of life, echocardiographic outcome, costs and efficiency associated with IE care. Statistical analysis will be performed with a non-inferiority margin of 10% and a one-sided 2.5% type I error.Ethics and disseminationWritten informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS-Region Centre-Ouest 1, 2015-R26, 23 February 2016). Study findings will be published in peer-reviewed journals and disseminated through presentation at relevant national and international conferences.Trial registration numberEudraCT Number: 2015-002371-16 andNCT02701608NCT02701595.

To assess: (1) the prevalence of convexity subarachnoid hemorrhage (cSAH) in infective endocarditis (IE); (2) its relationship with IE features; (3) the associated lesions; (4) whether cSAH is a predictor of future hemorrhage; (5) whether cSAH could cause cortical superficial siderosis (cSS). We retrospectively evaluated the MRI data in 240 IE-patients: At baseline, the location of cSAH and associated lesions; at follow-up, the occurrence of new lesions and of cSS. Patients with and without cSAH were compared. There were 21 cSAH-IE patients without (Group 1a) and 10 with intracranial infectious aneurysms (IIAs) (Group 1b). cSAH was revealed by headache (16.1%), confusion (9.7%), acute meningeal syndrome (3.2%) and was incidental in 71%. In most cases, the cSAH was: in the frontal (61.3%) and the parietal lobe (16.1%), unifocal, and mainly localized within a single sulcus (80.7%), appearing as a thick intrasulcal dark line on T2* in 70% of IIA patients. Valvular vegetations (87.1%, p

Background Increased access to heart valves through early surgery and progress in molecular microbiology have reduced the proportion of infective endocarditis (IE) with no microbiological documentation and increased the proportion of IE associated with unusual microorganisms. Methods We performed an ancillary study of a large prospective population-based survey on IE. Unusual-microorganism IE was defined as definite IE (Duke-Li criteria) due to microorganisms other than streptococci, staphylococci, or enterococci. Results Of 471 cases of documented IE, 46 (9.8%) were due to unusal microorganisms; the following were involved in >1 case: Candida albicans (n = 4), Cutibacterium acnes (n = 4), Pseudomonas aeruginosa (n = 3), Cardiobacterium hominis (n = 3), and Coxiella burnetii (n = 2). Cases were documented with blood cultures (n = 37, 80.4%), heart valve polymerase chain reaction (PCR; n = 5), heart valve culture (n = 2), PCR on vertebral biopsy (n = 1), or serology (n = 1). As compared with IE due to staphylococci, streptococci, or enterococci (n = 420), IE due to unusual microorganisms occurred more frequently in patients with previously known heart disease (69.0% vs 44.3%; P = .002), prosthetic valve (40.5% vs 18.1%; P = .0006), longer duration of fever (mean, 35.1 ± 46.8 days vs 12.5 ± 17.8; P = .003), and who were more often nosocomial (38.1% vs 20.2%; P = .02). Conclusions In this population-based study, 9.8% of IE cases were due to unusual microorganisms, with a predominance of anaerobes, yeast, and gram-negative bacilli. As compared with IE related to staphylococci, streptococci, or enterococci, IE cases related to unusual microorganisms were associated with previously known heart disease, prosthetic valve, longer duration of fever, and nosocomial acquisition. Trial registration ORCID 0000-0003-3617-5411, In this population-based study, 10% of endocarditis were due to microorganisms other than staphylococci, streptococci, and enterococci. These included anaerobes, yeasts, or Gram-negative bacilli, with an increased risk in patients with heart disease, prosthetic valve, prolonged fever, and nosocomial endocarditis.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) suffers from low sensitivity for identifying infective endocarditis (IE) ([1][1],[2][2]), partly because of the blurring effect resulting from the mobility of IE foci. This exploratory study aimed to examine whether the detectability of

Aim Anal dysplasia is caused by chronic infection with the human papillomavirus and exposes to the risk of anal cancer. Usually during a surgery for anal condylomas only one or two biopsies on visible lesions are performed to classify the level of dysplasia. The aim of this study was to evaluate the distribution of dysplasia anal grade among patients operated on for multiple anal condylomas with no macroscopic differences. Method Cross-sectional study of patients operated on for multiple anal condylomas including a mapping of dysplasia by performing systematically for each patient one biopsy on visible lesion from each of the 4 quadrants on anal margin and in anal canal. All biopsies were read independently by 2 different pathologists. Results Among 72 patients, 60 were men, 48 were HIV-infected with a median age of 37.5 years. The proportion of high-grade squamous intraepithelial lesion (HSIL) was higher in the anal canal (41.7%) compared to the margin (20.8%) (p= 0.004). HSIL frequency did not differ according to the quadrant (anterior, posterior, right or left) of the two areas. HSIL on anal canal was not associated with HSIL on anal margin and vice versa (p=0.39). Neither age nor sex was associated to HSIL but HIV positivity increased the risk of HSIL on the anal margin (p=0.01). Conclusion Anal dysplasia is heterogeneously distributed in the anal canal as well as between anal canal and anal margin. The diagnostic of the grade of dysplasia for a person should require multiple biopsies on the canal and anal margin.

International audience; Influenza vaccine adherence remains low. Communication of virological diagnosis to adults hospitalized with influenza-like illness (ILI) could improve their willingness to be subsequently vaccinated. We prospectively assessed, in adults hospitalized with ILI in six French university hospitals, their willingness to be vaccinated against influenza in the subsequent season, both before and after the communication of RT-PCR Influenza laboratory result; we identified then the determinants associated with the willingness to be vaccinated. A total of 309 patients were included during the 2012-2013 and 2013-2014 influenza seasons; 43.8% reported being vaccinated against influenza for the current season; before communication of influenza laboratory results, 65.1% reported willingness to be vaccinated during the subsequent season. Influenza was virologically confirmed in 103 patients (33.3%). The rate of vaccine willingness increased to 70.4% (p=0.02) after communication of influenza laboratory results. Factors independently associated with the willingness to be vaccinated were the perception of influenza vaccine benefits (adjusted relative risk (aRR) 1.06, 95%CI 1.02-1.10), cues to action (aRR 1.08, 95%CI 1.03-1.12), current season influenza vaccination (aRR 1.38, 95%CI 1.20-1.59) and communication of a positive influenza laboratory result (aRR 1.18, 95%CI 1.03-1.34). This last was associated with the willingness to be vaccinated only in the subpopulation of patients not vaccinated (aRR 1.53, 95%CI 1.19-1.96). In patients hospitalized with ILI, communication of a positive influenza diagnostic led to a better appreciation of the disease's severity and increased the willingness to be vaccinated. This approach might be particularly beneficial in patients who do not have a history of influenza vaccination.

Background The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study has reported an increased risk of cardiovascular diseases in people with human immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV). Our objective was to evaluate associations between ATV or DRV exposures and the risk of myocardial infarction (MI) in a nested case-control study within ANRS-CO4 French Hospital Database on HIV (FHDH). Methods Cases were individuals who had a first validated MI between 2006 and 2012. Up to 5 controls were selected at random with replacement among individuals with no history of MI, followed at the time of MI diagnosis, and matched for age and sex. Conditional logistic regression models were used to adjust for potential confounders (MI risk factors and HIV-related parameters) and for cumulative exposure to each antiretroviral drug (ARV). Results Overall, 408 MI cases and 1250 controls were included: 109 (27%) cases and 288 (23%) controls had been exposed to ATV, and 41 (10%) cases and 107 (9%) controls had been exposed to DRV. There was no significant association between exposure to ATV (adjusted odds ratio [OR] = 1.54; 95% confidence interval [CI], .87–2.73) or DRV (adjusted OR = 0.51; 95% CI, .11–2.32) and the risk of MI. Conclusions In FHDH, exposures to ATV or to DRV were not significantly associated with the risk of MI, adjusting for complete ARV history, contrary to the analysis in DAD.

International audience; Objectives - To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). Methods - This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset 65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. Conclusions - Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.

BackgroundSevere bacterial infections are the first cause of morbidity in people with human immunodeficiency virus (PWH). We aimed to assess their incidence and to analyze their determinants.MethodsWe studied human immunodeficiency virus (HIV)-1-infected individuals aged at least 15 years and prospectively followed between 2006 and 2015 in the French Hospital Database on HIV. The Andersen and Gill model was used to calculate the adjusted hazard ratios (HRs), focusing on heavy alcohol use and neutrophil function-altering comorbidities.ResultsOf 25 795 participants, 1414 developed 1883 severe bacterial infections. Between 2006 and 2009 and 2013 and 2015, the incidence fell from 13.2 (95% confidence interval [CI], 12.3–14.1) to 7.1 (95% CI, 6.3–7.8) per 1000 person-years. Heavy alcohol use was associated with an increased risk of severe bacterial infection (HR = 1.3, 95% CI = 1.1–1.7 for 40–80 g/day and HR = 1.6, 95% CI = 1.2–2.1 for >80 g/day), as were diabetes, chronic kidney disease, and end-stage liver disease (HR = 1.2, 95% CI = 1.0–1.4 when 1 comorbidity; HR = 2.3, 95% CI = 1.6–3.4 when more than 1 comorbidity), and nonacquired immune deficiency syndrome-defining malignancy (HR = 2.0; 95% CI, 1.6–2.4).ConclusionsHeavy alcohol use was associated with an increased risk of severe bacterial infection, as were neutrophil function-altering comorbidities. Controlled-drinking approaches should be promoted and comorbidity management should be strengthened in PWH.

International audience; Among 143 patients of the VIRSTA cohort study with Staphylococcus aureus bacteremia and an arthroplasty implanted for more than a year, S. aureus periprosthetic joint infection was observed in 19%. Signs of infection (pain and swelling) were always present, in median 1 day (range, 0-21 days) after onset of bacteremia. Staphylococcus aureus has both a high potential for metastatic infection and a high affinity for foreign material. Possible prosthesis infection is of clinical concern in all patients with preexisting prosthetic materials experiencing S. aureus bloodstream infection (SAB). Prosthetic joints are especially prone to infection during the course of bacteremia, with a risk of infection much higher with S. aureus than with other microorganisms, 20% vs 7%, in a recent prospective study [1]. As early intervention with debridement in prosthetic joint infection (PJI) is paramount to retain the implant and to prevent infection relapse; eliminating PJI after SAB is important. However, additional data are needed to better describe the clinical characteristics of PJI after SAB in particular time lapses and whether systematic imaging of the prosthesis could be necessary after SAB. We described the frequency and clinical presentation of PJIs observed among patients with prosthetic joints implanted for >1 year before bacteremia and enrolled in the VIRSTA study, a multicenter prospective cohort study of patients with SAB.

International audience; Objectives. To prevent infective endocarditis in patients with predisposing cardiac conditions, antibiotic prophylaxis is recommended worldwide, except in the United Kingdom. To determine the relevance of this strategy, investigating how the current guidelines are applied is crucial. The first aim of this study was to assess dentists' implementation of the current guidelines. The secondary aims were to identify relevant areas to improve the training of dentists and to determine temporal trends in practitio-ners' attitudes by comparison with 2 previous surveys conducted in 1991 and 2001.Study Design. An electronic national survey was sent to the 12,000 member practitioners of the French Union for Oral Health.Results. Even though 58.9% of the respondents stated that their knowledge of current guidelines was good, a scoring system showed that only 34.5% had overall knowledge of these guidelines.Conclusions. This study revealed relevant areas to improve the training of dentists, such as knowledge of some cardiac conditions, the potential side effects of the antibiotics used, and the pathogenesis of infective endocarditis. Consequently, dentists' knowledge should be improved before any conclusions can be drawn on the relevance of this antibiotic prophylaxis strategy and its influence on infective endocarditis incidence.

International audience; BACKGROUND:Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV.METHODS:The ANRS 144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo-controlled phase 3 trial was done at 30 clinical hospital sites in France. People living with HIV who had smoked at least ten cigarettes per day for 1 year or longer, were motivated to stop smoking, were not dependent on another psychoactive substance, and had no history of depression or suicide attempt were eligible. Using a computer-generated randomisation sequence, we allocated (1:1) the patients to receive either varenicline titrated to two 0·5 mg doses twice daily or placebo twice daily for 12 weeks, plus face-to-face counselling. Patients and investigators were masked to treatment group allocation. Patients who were not abstinent at week 24 were offered open-label varenicline for 12 additional weeks. The primary outcome was the proportion of smokers continuously abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide in exhaled air. Primary analyses were done in both the intention-to-treat (ITT) population and modified ITT (mITT) population, which comprised all patients who took at least one tablet of their assigned study treatment. The safety analyses were done in the mITT population. The trial is registered at ClinicalTrials.gov, number NCT00918307. The trial status is complete.FINDINGS:From Oct 26, 2009, to Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were randomly assigned to the varenicline group (n=123) or the placebo group (n=125). After randomisation, one participant initially assigned to the placebo group was excluded from the ITT analysis for a regulatory reason (no French health-care coverage). 102 patients in the varenicline group and 111 patients in the placebo group received at least one dose of their assigned treatment and were included in the mITT analysis. In the ITT analysis, varenicline was associated with a higher proportion of patients achieving continuous abstinence over the study period (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2·5 (95% CI 1·0-6·1; p=0·041). In the mITT analysis, varenicline was also associated with higher continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of 111 in the placebo group (adjusted OR 2·7, 95% CI 1·1-6·5; p=0·029). The incidence of depression was 2·4 per 100 person-years (95% CI 0·6-9·5; two [2%] of 102) in the varenicline group and 12·4 per 100 person-years (95% CI 6·9-22·5; 11 [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18 cardiovascular events: six (6%) of 102 people in the varenicline group and eight (7%) of 111 people in the placebo group.INTERPRETATION:Varenicline is safe and efficacious for smoking cessation in people living with HIV and should be recommended as the standard of care.FUNDING:The French National Institute for Health and Medical Research (INSERM)-French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Pfizer.

We present here the proceedings of the 5th seminar on emerging infectious diseases, held in Paris on March 22nd, 2016, with seven priority proposals that can be outlined as follows: encourage research on the prediction, screening and early detection of new risks of infection; develop research and surveillance concerning transmission of pathogens between animals and humans, with their reinforcement in particular in intertropical areas (“hot-spots”) via public support; pursue aid development and support in these areas of prevention and training for local health personnel, and foster risk awareness in the population; ensure adapted patient care in order to promote adherence to treatment and to epidemic propagation reduction measures; develop greater awareness and better education among politicians and healthcare providers, in order to ensure more adapted response to new types of crises; modify the logic of governance, drawing from all available modes of communication and incorporating new information-sharing tools; develop economic research on the fight against emerging infectious diseases, taking into account specific driving factors in order to create a balance between preventive and curative approaches.

To assess the diagnostic value of contrast-enhanced MRA (CE MRA) and CE 3D-T1 for identifying intracranial infectious aneurysms (IIAs) in infective endocarditis (IE) with digital substraction angiography (DSA) as reference.Twenty-one IE patients (14 males; mean age: 53 years) with 30 IIAs, diameter ranging 1.5-15 mm (3mm, n = 14, 46.7%; 3-5 mm, n = 12,40%), underwent CE MRA and CE 3D-T1 at 1.5 T. Two readers evaluated images for aneurysm detection, characterization, quality of visualization. DSA was obtained at a median of 3 days (range 1-15) after MRI.The sensitivity, specificity, positive and negative predictive values and accuracy of IIA detection were respectively: 80%, 100%, 100%, 82.3%, 90% for CE MRA and 86.7%, 100%, 100%, 88.2%, 93.3% for CE 3D T1 compared to DSA. No significant difference was observed between CE MRA and CE 3D-T1 for accuracy and quality of visualization. All IIAs of ≥3 mm in diameter (16/30; 53.%) were identified by both sequences, which were also able to detect IIAs ≤ 3 mm (n = 14/30, 46.7%). False negatives were observed with both sequences for 4 IIAs of2 mm, 3 being compressed by hemorrhagic lesions. Two other IIAs of2 mm were overlooked by CE MRA. CE 3D-T1 overestimated IIAs luminal diameter by 8% relatively to DSA (P = NS). Intra and inter-observer agreement were good and similar with both methods.Both CE MRA and CE 3D-T1 have good accuracy compared to DSA detection and characterization of IIAs. CE 3D-T1 also evaluates anatomical relationships of IIAs, which could help DSA location and endovascular treatment.

Infectious encephalitis is a severe disease leading to a high mortality and morbidity. The most frequent causes include Herpes simplex virus, Varicella Zoster virus, Listeria monocytogenes, and Mycobacterium tuberculosis. Urgent treatment is required (anti-infective therapy and nonspecific supportive care). The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review.

Background: Longitudinal strain has been proposed as a sensitive marker of left ventricular systolic dysfunction. However its prognostic value in patients with aortic stenosis (AS) remains debated....

The prognostic value of N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) in aortic stenosis (AS) is still being debated. We sought to evaluate the determinants of Nt-proBNP in AS and its prognostic value in asymptomatic patients.Patients with pure isolated at least mild degenerative AS enrolled in our prospective cohort (2006-2013) constituted our population. Clinical and biological measurements as well as echocardiographic evaluations were performed at study entry for all patients. Severe AS was defined by a valve area1cmWe enrolled 809 patients. Nt-proBNP increased with AS severity (p0.0001) and symptomatic status (p0.0001) but there was a wide overlap between groups of AS severity or symptomatic status. Nt-proBNP was the result of complex interactions between multiple determinants, including AS severity and symptomatic status but also age (p=0.0008), history of coronary artery disease (p=0.03), rhythm (p=0.007) and diastolic function (p0.0001). Consequently, in asymptomatic patients with moderate/severe AS, normal ejection fraction and in sinus rhythm, Nt-proBNP was associated with AS-related events in univariate analysis (p=0.009) but not after adjustment for AS severity (p=0.12). Repeated Nt-proBNP measurements at one year did not improve their predictive value (p=0.43).This study highlights the limitations of Nt-proBNP in AS and raises caution regarding its use, at least as a single factor, in the decision-making process regarding asymptomatic patients with AS.

Background: Whether risk-stratification in aortic valve stenosis (AS) should rely on a single hemodynamic parameter or a combination of hemodynamic parameters is still debated. We aimed to evaluate the prognostic value of mean pressure gradient (MPG), aortic valve area (AVA), and the dimensionless index (DI) in patients with AS and to test whether their combination provides additional prognostic information.Methods: We enrolled 319 asymptomatic patients with AS (90 mild, 173 moderate, and 56 severe AS). All patients were prospectively followed on a yearly basis and AS-related events (sudden death, heart failure, or new onset of AS-related symptoms) were collected.Results: After a mean follow-up of 3.1±1.7 years, an AS-related event occurred in 84 patients (26%). When considered in isolation, after adjustment for age, sex, history of coronary artery disease, valve anatomy, and left ventricular ejection fraction, each parameter (MPG, AVA, and DI) independently predicted the occurrence of AS-related ...

Introduction Les infections bacteriennes severes sont la premiere cause de morbidite chez les personnes vivant avec le VIH (PVVIH). Nous avons cherche a evaluer leur incidence et a analyser leurs determinants. Materiels et methodes La population d’etude etait celle des PVVIH âgees d’au moins 15 ans suivies dans une cohorte prospective nationale multicentrique entre 2006 et 2015. Le modele d’Andersen et Gill a ete utilise pour estimer le risque d’infection bacterienne severe, y compris recidivante, en particulier en cas de consommation elevee d’alcool ou en presence d’une comorbidite alterant la fonction neutrophile (diabete, maladie renale chronique, cirrhose, cancers). Resultats Parmi 25 795 participants, 1414 ont developpe 1883 infections bacteriennes severes, incluant 1132 pneumonies, 154 infections des voies urinaires, 136 infections de la peau et des tissus mous, 70 colites, 6 meningites, 14 endocardites, 94 infections intra-abdominales, 33 arthrites, osteomyelites ou osteites, 3 myosites, 236 bacteriemies ou sepsis d’autre origine et 3 chocs septiques d’autre origine. Entre 2006–2009 et 2013–2015, l’incidence a diminue de 13,2 (IC95 %: 12,3–14,1) a 7,1 (IC95 %: 6,3–7,8) pour 1000 personne-annees (ratio du taux d’incidence 0,54, IC95 %: 0,47–0,60). Une consommation elevee d’alcool etait associee a un risque accru d’infection bacterienne severe, avec un risque relatif ajuste (RRa) a 1,4 (IC95 %: 1,1–1,7) pour 40–80 g/jour et 1,6 (IC95 %: 1,3–2,1) pour > 80 g/jour. C’etait le cas egalement pour le diabete, la maladie renale chronique et la cirrhose, avec un RRa a 1,2 (IC95 %: 1,0–1,4) pour une seule comorbidite et 2,3 (IC95 %: 1,6–3,4) lorsque deux comorbidites etaient presentes, ainsi que pour les cancers non classants et classants, avec un RRa respectivement a 2,0 (IC95 %: 1,6–2,4) et 1,4 (IC95 %: 1,2–1,7). Conclusion Sur une periode de 10 ans, l’incidence des infections bacteriennes severes a diminue de moitie. Une consommation elevee d’alcool et les comorbidites alterant la fonction neutrophile etaient associees a un risque accru. Le controle de la consommation d’alcool et la prise en charge des comorbidites doivent etre renforcees chez les PVVIH.

Infective endocarditis (IE) is a rare but potentially devastating complication. Recent European guidelines [(1)][1] have implemented fluorine-18-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT), radiolabeled white blood cell (WBC) single-photon emission

Acute kidney injury (AKI) is associated with high case fatality in infective endocarditis (IE), but epidemiological data on the frequency of AKI during IE is scarce. We aimed to describe the frequency and risk factors for AKI during the course of IE using Kidney Disease: Improving Global Outcomes consensual criteria.Using the French hospital discharge database (French acronym PMSI), we retrospectively reviewed the charts of 112 patients presenting with a first episode of probable or definite IE between January 2010 and May 2015.Seventy-seven patients (68.8%) developed AKI. In univariate analysis, risk factors for AKI were cardiac surgery for IE (n=29, 37.7% vs. n=4, 1.4%, P0.0005), cardiac failure (n=29, 36.7% vs. n=1, 2.9%, P0.0005), diabetes mellitus (n=14, 18.2% vs. n=1, 0.9%, P=0.034), and prosthetic valve IEs (n=24, 31.2% vs. n=4, 11.4%). No differences were observed for gentamicin exposure (n=57, 64% vs. n=32, 86.5%, P=0.286). Prosthetic valve IE, cardiac failure, and vancomycin exposure were independently associated with AKI with respective odds ratio of 5.49 (95% CI 1.92-17.9), 4.37 (95% CI 4.37-465.7), and 1.084 (1.084-16.2). Mean length of hospital stay was significantly longer in patients presenting with AKI than in controls (respectively 52.4±22.1 days vs. 39.6±12.6, P0.005).AKI is very frequent during IE, particularly in patients with prosthetic valve IE, cardiac failure, and those receiving vancomycin.

Although the global deleterious impact of antibiotics on the intestinal microbiota is well known, temporal changes in microbial diversity during and after an antibiotic treatment are still poorly characterized. We used plasma and fecal samples collected frequently during treatment and up to one month after from 22 healthy volunteers assigned to a 5-day treatment by moxifloxacin (n = 14) or no intervention (n = 8). Moxifloxacin concentrations were measured in both plasma and feces, and bacterial diversity was determined in feces by 16S rRNA gene profiling and quantified using the Shannon index and number of operational taxonomic units (OTUs). Nonlinear mixed effect models were used to relate drug pharmacokinetics and bacterial diversity over time. Moxifloxacin reduced bacterial diversity in a concentration-dependent manner, with a median maximal loss of 27.5% of the Shannon index (minimum [min], 17.5; maximum [max], 27.7) and 47.4% of the number of OTUs (min, 30.4; max, 48.3). As a consequence of both the long fecal half-life of moxifloxacin and the susceptibility of the gut microbiota to moxifloxacin, bacterial diversity indices did not return to their pretreatment levels until days 16 and 21, respectively. Finally, the model characterized the effect of moxifloxacin on bacterial diversity biomarkers and provides a novel framework for analyzing antibiotic effects on the intestinal microbiome.

Cardiac implantable electronic devices (CIEDs) chronic infection diagnosis is challenging because the clinical presentation is frequently misleading and echocardiography may be inconclusive. The aim of this study was to evaluate the diagnostic value ofForty-eight consecutive patients with suspicion of CIED infection who underwent bothIn the overall study population, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were respectively 80%, 91%, 80%, and 91% forNuclear imaging can improve the diagnostic performances of the Duke-Li score at admission in a selected population of patients with suspected CIED infection, particularly when the infection was initially graded as possible. Whenever possible, imaging should be performed before or early after antibiotic initiation.

Background: Cardiac implantable electronic devices (CIEDs) chronic infection diagnosis is challenging because the clinical presentation is frequently misleading and echocardiography may be inconclusive. The aim of this study was to evaluate the diagnostic value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and radiolabeled white blood cells single photon emission CT/CT in a cohort of patients who underwent both scans for suspicion of CIED infection and inconclusive routine investigations. Methods: Forty-eight consecutive patients with suspicion of CIED infection who underwent both 18 F-fluorodeoxyglucose positron emission tomography/CT and white blood cell single photon emission CT/CT in a time span ≤30 days were retrospectively included. The final diagnosis of CIED infection by the endocarditis expert team was based on the modified Duke-Li classification at the end of follow-up. 18 F-Fluorodeoxyglucose positron emission tomography/CT and white blood cell single photon emission CT/CT scans were independently analyzed blinded to the patients’ medical record. Results: In the overall study population, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were respectively 80%, 91%, 80%, and 91% for 18 F-fluorodeoxyglucose positron emission tomography/CT and 60%, 100%, 100%, and 85% for white blood cell single photon emission CT/CT. Addition of a positive nuclear imaging scan as a major criterion markedly improved the Duke-Li classification at admission. Semiquantitative parameters did not allow to discriminate between definite and rejected CIED infection. Prolonged antibiotic therapy before imaging tended to decrease the sensitivity for both techniques. Conclusions: Nuclear imaging can improve the diagnostic performances of the Duke-Li score at admission in a selected population of patients with suspected CIED infection, particularly when the infection was initially graded as possible. Whenever possible, imaging should be performed before or early after antibiotic initiation.

Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)

The severity of left ventricular (LV) remodelling is only partially related to the severity of aortic valve stenosis; additional factors, including diabetes, insulin resistance, obesity and metabolic syndrome, may play important roles. Epicardial adipose tissue (EAT), now considered as a metabolically active organ, is also linked to these factors.To analyse the association between EAT volume measured using computed tomography and LV remodelling in a prospective cohort of patients with aortic stenosis.Consecutive asymptomatic patients with at least mild degenerative aortic stenosis enrolled in a prospective cohort that aimed to assess the determinants of aortic stenosis occurrence and progression constituted our population.We enrolled 143 patients (78±5 years; 65% men). Mean LV mass and EAT volume were 219±64g and 134±56mL, respectively. LV hypertrophy was diagnosed in 86 patients (60%), and concentric hypertrophy (32%) was the main remodelling pattern. EAT was associated with body mass index (P0.001) and body surface area (P0.001), but not with age (P=0.33) or aortic stenosis severity (all P0.10). EAT was correlated with LV mass (r=0.41; P0.0001), and after adjustment for age, sex, body mass index/body surface area, hypertension, waist circumference, low-density lipoprotein cholesterol and aortic stenosis severity, EAT was independently associated with LV mass (P=0.01/P=0.02). Similar results were found when EAT and LV mass index (adjusted for body surface area) were considered instead of absolute values (P=0.04).In this prospective cohort of patients with aortic stenosis, EAT volume was independently associated with LV mass. Further studies are warranted to elucidate the underlying mechanisms of this link.

Indications of antibiotic prophylaxis are restricted to the patients at highest risk of infective endocarditis undergoing at-risk dental procedures. Guidelines emphasize the importance of daily non-specific oral and cutaneous hygiene. Restorative dentistry, endodontic and periodontal therapy can be performed in patients at high risk of endocarditis, provided careful follow-up is effective. The use of dental implants is no longer contra-indicated in patients at high risk of endocarditis, but the decision be based on an individual analysis of risk factors of implant failure. Evaluations of practices show that prevention of endocarditis is not sufficiently implemented. All health professionals should be aware of the importance of prevention measures of heathcare-associated infective endocarditis. Endocarditis prophylaxis cards are made available to patients and health professionals to make them aware of the endocarditis prophylaxis.

Objective To assess the proportion of patients meeting the 2010 SPILF-AFSSAPS guiding criteria for Streptococcus pneumoniae in patients consulting at the emergency departments of four French university hospitals for acute community-acquired pneumonia (CAP) suspicion. Patients and methods The PACSCAN study prospectively included 319 patients. Medical history, clinical, biological, and radiological presentations were collected. An adjudication committee retrospectively classified the diagnostic certainty based on the initial chest CT scan data and the follow-up data up to Day 28. S. pneumoniae was looked for according to the clinician's choice of blood culture, pneumococcal urinary antigen test, nasopharyngeal PCR, and/or sputum microbiological examination. Results All patients (100%) met at least one criterion for S. pneumoniae CAP and six (2%) met all criteria. The distribution of criteria ranged from 32% (chest pain criterion) to 86% (age ≥ 40 years criterion). These figures were respectively 100%, 3%, 38%, and 82% when the study population was restricted to the 139 patients with definite or probable CAP, according to the adjudication committee. Taking into account the microbiological results, the criteria taken one by one or combined did not make it possible to differentiate the 19 S. pneumoniae CAP from the other CAPs. Conclusion The 2010 SPILF-AFSSAPS guiding criteria for S. pneumoniae CAP are found in very variable proportions and do not, in their current form, make it possible to accurately guide towards a pneumococcal etiology in patients included in the PACSCAN study.

Background One of the major reasons to stop antibiotic prophylaxis (AP) to prevent infective endocarditis (IE) in the United Kingdom but not in the rest of the world was that it would result in more deaths from fatal adverse drug reactions (ADRs) than the number of IE deaths. The main aim of this study was to quantify and describe the ADRs with amoxicillin or clindamycin for IE AP. The second aim was to infer a crude incidence of anaphylaxis associated with amoxicillin for IE AP. Material and Methods The Medical Dictionary for Regulatory Activities (MedDRA) was used to group ADRs for IE AP using the broad Standardized MedDRA Queries “Anaphylactic reaction, Amoxicillin, Clindamycin, Clostridium Difficile infection” to the French Pharmacovigilance Database System. From this first-line collection, we selected all cases occurring for IE AP and ultimately, the cases for IE AP for a dental procedure. Then, each case was analyzed. Results Of 11639 first-line recorded ADRs, 100 were for IE AP but no fatal anaphylaxis to amoxicillin or clindamycin and no C. difficile infection associated with clindamycin were identified. Only 17 cases of anaphylaxis to amoxicillin related to dental procedures were highlighted. The estimation of the crude incidence rate of anaphylaxis associated with amoxicillin for IE AP for invasive dental procedure was 1/57 000 (95% CI 0.2-0.6). Conclusions Fatal or severe ADRs with amoxicillin or clindamycin is not a rational argument to stop IE AP before invasive dental procedures. Key words:Infective endocarditis, antibiotic prophylaxis, anaphylaxis, adverse drug reaction, amoxicillin, clindamycin, pharmacovigilance.

Contribution of the new guidelines for the management of infective endocarditis. New guidelines for the management of infective endocarditis (IE) have been recently published both in United States and in Europe. Although identification responsible micro-organism by blood culture and assessment of cardiac lesions by echocardiography remain the cornerstone of the diagnosis of IE, recommendations insist on the additive interest of multimodality imaging including cerebral MRI, MSCT and nuclear imaging (Pet CT) in the diagnosis of both cardiac and extracardiac lesions of IE. Regarding prophylaxis, antibiotic prophylaxis before dental procedures at risk in high risk patients is still recommended. Furthermore, all patients should be advised of the importance of dental and cutaneous hygiene. Recommendations on antibiotic therapy no longer advocate the use of aminoglycosides in case of staphylococcal native IE. Finally, recommendations strongly support the management of patients with IE in reference centres by a specialized team (the 'Endocarditis Team') including cardiologists, ID specialists, cardiac surgeons, microbiologists, imaging specialists and any specialist implied in the management of IE patients.Apport des nouvelles recommandations pour la prise en charge de l’endocardite infectieuse. De nouvelles recommandations sur la prise en charge de l’endocardite infectieuse ont été publiées à la fois au niveau européen et au niveau américain en 2015. Sur le plan diagnostique, si l’identification du germe responsable par les hémocultures et la mise en évidence de lésions cardiaques par l’échocardiographie restent les éléments de base, les nouvelles recommandations, notamment européennes, insistent sur l’apport complémentaire des autres imageries, notamment la tomodensitométrie corps entier, l’imagerie cérébrale par résonance magnétique et la tomographie par émission de positons, dans le diagnostic des atteintes cardiaques et/ou des complications extracardiaques de l’endocardite infectieuse. En termes de prévention, le principe d’une antibioprophylaxie avant un geste dentaire à risque chez les sujets à haut risque reste maintenu tout en insistant sur l’importance de l’hygiène bucco-dentaire et de la prévention des portes d’entrée cutanées. Sur le plan thérapeutique, la principale nouveauté de ces recommandations est qu’il est désormais recommandé de ne plus utiliser d’aminosides pour le traitement des endocardites infectieuses à staphylocoques sur valve native. Enfin, les recommandations insistent sur la nécessité d’une prise en charge de tout patient atteint d’endocardite infectieuse dans un centre expert disposant d’une « endocarditis team » composée d’infectiologues, de cardiologues, de chirurgiens cardiaques ainsi que de réanimateurs, de microbiologistes, de radiologues et tout autre spécialiste impliqué dans la gestion de ces patients.

Acute subdural hematoma (ASDH) revealing mycotic aneurysm (MA) is an exceptional occurrence. We report 2 cases of MA-related pure ASDH in the course of infective endocarditis (IE) without history of head trauma, hypertension or coagulopathy. Case 1: A 54-year-old man presented with a 10-day history of headache, fever. At admission neurologic examination and Brain-CT were normal. Blood cultures showed Streptococcus bovis. MRI 5 days later revealed ischemic spots and minime ASDH over the right convexity. Cerebral angiography, revealed a 3 mm saccular aneurysm at the bifurcation of a distal branch of the right posterior cerebral artery (PCA). Case 2: A 42-year-old man presented with a 8-day history of fever, and worsening headache. Mitral regurgitation was evidenced. A methicillin-sensitive staphylococcus aureus left-sided IE was diagnosed. Pre- and post-contrast Brain-CT were normal. He presented 15 days later a secondarily generalized status epilepticus. Brain CT showed an ASDH over the convexity with falco-tentorial extension, midline shift and temporal herniation. It was removed in emergency. Cerebral angiography revealed a MA of a peripheral branch of the left PCA. The 2 patients were successfully treated by endovascular glue embolization and recovered without complications. Even rare, ruptured MA should be considered as a cause of pure ASDH of unknown origin. As MA can be missed on CT- and MR-Angiography because of mass effect, cerebral angiography may be mandatory.

Background Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs. Methods We used a prospective cohort including all consecutive patients admitted through the emergency department’s (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR. Results 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively. Conclusion Patients’ characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.

Aim Anal screening is recommended in HIV-positive patients, especially men who have sex with men (MSM), due to an increased incidence of anal cancer. The optimal screening methods are not generally agreed. Method Screening for anal lesions by anorectal examination, including anoscopy, was offered to HIV-positive outpatients in a tertiary care university hospital regardless of gender or sexual orientation. Results Among the 1206 screened patients (701 MSM, 247 heterosexual men, 258 women), 311 (26%) had histologically proven lesions related to human papilloma virus (HPV) (34% MSM, 14% heterosexual men, 14% women); 123 (10%) had low-grade dysplasia and 70 (6%) high-grade dysplasia. Seven anal cancers were also diagnosed. Determinants of any lesion were age < 45 years [OR = 1.56 (95% CI, 1.16–2.11)], a CD4 count of < 200/mm3 [OR = 2.54 (1.71–3.78)], receptive anal intercourse [OR =3.03 (2.06–4.47)], sub-Saharan African origin [OR = 0.53 (0.33–0.85)], and history of HPV-related lesion [OR = 1.84 (1.35–2.51)]. These determinants were similar for all different grades of dysplasia. In patient subgroup analysis, receptive anal intercourse, the CD4 cell count and a history of HPV lesions were determinants of HPV-positivity in all patients, whereas age was only a determinant in men. Conclusion Anoscopy is an alternative method for anal screening in an HIV-positive population. This screening has to be compared with other tools in populations at high risk of anal cancer.

International audience; Objective:To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers.Design:Multicenter, interventional study.Setting:Two ICUs and one clinical research center.Subjects:Anemic critically ill patients treated with IV iron and healthy volunteers.Interventions:IV infusion of 100 mg of iron sucrose.Measurements and Main Results:Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7–9.2]) (men, 25 [66%]; aged 68 yr [48–77]; Simplified Acute Physiology Score II, 48.5 [39–59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29–50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation—8α-isoprostanes, protein oxidation—advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5–12.9] vs 4.6 pmol/L [3.5–5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes.Conclusions:In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.

Introduction Le virus respiratoire syncytial (VRS) est responsable d’infections respiratoires chez les sujets âges avec comorbidites. L’objectif etait de comparer les caracteristiques et l’evolution intra et extra-hospitaliere des adultes hospitalises avec une infection a VRS a ceux ayant une infection grippale. Materiels et methodes Les adultes hospitalises pour une infection respiratoire aigue (IRA) ont ete prospectivement inclus dans une etude multicentrique menee dans cinq hopitaux universitaires durant deux saisons hivernales consecutives (2017/2018 et 2018/2019). Les patients presentant une infection a VRS et une grippe, confirmees par RT-PCR sur un prelevement nasopharynge, ont ete compares. Des modeles de regression de Poisson a variance robuste ont ete utilises pour estimer les ratios de prevalence (RP) associes a la morbi-mortalite hospitaliere et a l’evolution extra-hospitaliere (defini comme une nouvelle hospitalisation ou le deces dans les 3 mois suivant la sortie de l’hopital) entre les patients VRS et grippes apres ajustement sur les facteurs de confusion potentiels. Resultats Au total, 1 428 adultes hospitalises pour IRA ont ete inclus, l’âge median etait de 72 ans (IIQ 60-82), 55 % etaient des hommes (790/1428) et 87 % avaient une maladie chronique sous-jacente (1250/1428). Le VRS a ete detecte dans 8 % des cas (114/1428) et le virus grippal dans 31 % des cas (437/1428). Apres exclusion des co-infections (n = 6), l’âge median etait de 74 ans (IIQ 64–83) chez les patients VRS positifs et de 72 ans (IIQ 60–82) chez les grippes positifs (p = 0,06). Les patients VRS positifs presentaient plus frequemment des antecedents de pathologies respiratoires chroniques (52 % (56/108) contre 39 % (166/431), p = 0,012) ou de pathologies cardiaques chroniques (52 % (56/108) contre 41 % (176/431), p = 0,039) que les patients grippe positifs. La duree mediane d’hospitalisation etait plus elevee pour le VRS que pour la grippe (8 (IIQ, 5–13) contre 6 jours (IIQ, 4–11), p Conclusion La morbi-mortalite intra-hospitaliere associee aux infections a VRS confirmees etait plus importante que celle de la grippe soulignant la necessite d’un diagnostic standardise et du developpement de traitements et vaccins specifiques.

Introduction La proportion des professionnels de santé (PS) infectés à la suite d’un contact professionnel à risque modéré ou élevé de transmission (selon définition Santé Publique France) avec un sujet index COVID-19 n’est pas connue. Dans cette étude, nous évaluons l’évolution clinique, virologique et immunologique à la suite d’un contact à risque non protégé avéré et daté parmi les professionnels de santé. Matériels et méthodes Cette étude de cohorte prospective multicentrique (17 CHU) en cours, inclut des PS à la suite d’un contact à risque modéré/élevé de transmission. Sont effectués des prélèvements nasopharyngés répétés entre le jour du dernier contact à risque avec un sujet index COVID-19 (D0) et D14, un recueil journalier des symptômes entre D0 et D30, des prélèvements sanguins à visée sérologique à l’inclusion, D30, D90, D180 et D365. L’infection était considérée certaine à SARS-COV-2 en présence d’une PCR positive ou d’une séroconversion IgG entre D0 et D30. Elle était considérée comme probable en présence pendant ≥ 2 jours consécutifs, entre D0 et D30, d’au moins 1 symptôme général (fièvre, fatigue, myalgies, céphalées) et d’1 symptôme spécifique (toux, dyspnée, maux de gorge, congestion nasale, anosmie, diarrhée) en l’absence de PCR positive ou de séroconversion. La présente analyse porte sur les premiers sujets contacts PS du 1er centre recruteur disposant d’un suivi à D30 réalisé. Résultats Entre le 3 fev et le 27 avr 2020, 145 PS ont été inclus dans le premier centre recruteur (âge médian 35 ans, sex-ratio H/F : 0,3), dont 48/143 de personnel médical (33,5 %), 64/143 de personnel non médical (44,8 %) et 31/143 de personnel autre (21,7 %). Un contact à risque multiple avec ≥ 2 sujets index COVID-19 a concerné 28/145 PS (19,3 %). Le sujet index COVID-19 était au moins 1 patient COVID-19 pour 70/143 (49,1 %) et au moins 1 autre PS COVID-19 pour 85/143 (59,4 %). La durée cumulée du contact à risque était 60 min pour 58/143 (40,6 %). Le délai médian entre le dernier contact à risque avec le sujet index COVID-19 et l’inclusion était de 6 jours. Entre D0 et D30, 41/143 PS contacts (28,7 %) ([IC95 %] [21,3 % ; 36,1 %]) ont présenté une infection certaine à SARS-CoV-2 (20 PCR positives avec 1 séroconversion, 3 PCR positives sans séroconversion et 18 séroconversions isolées), qui était asymptomatique pour 10/41 (24,4 %). Cette proportion s’élevait à 46,9 % [38,7 % ; 55,0 %] quand les infections probables étaient aussi prises en compte. Conclusion La proportion des professionnels de santé (PS) infectés à la suite d’un contact professionnel à risque est très élevé (1/3 à ½ selon la définition retenue), dont ¼ des infections sont asymptomatiques.

Prevention of infective endocarditis has historically focused on oral health because oral streptococci are part of oral flora and once caused most cases of native valve infective endocarditis. Because no randomized clinical trial has ever been conducted to confirm the efficacy and safety of antibiotic prophylaxis of infective endocarditis, it is likely that the debate on indications for antibiotic prophylaxis of infective endocarditis will continue in the coming years. In the meantime, it is reasonable to propose antibiotic prophylaxis to patients at high risk of infective endocarditis before they undergo high-risk dental procedures. Prevention of healthcare-associated infective endocarditis should also be targeted through prevention of healthcare-acquired bacteraemia, and antibiotic prophylaxis before the implantation of cardiac implantable electronic devices. Other prevention options include preservation of good oral hygiene. In the future, prevention of Staphylococcus aureus endocarditis might rely on vaccines, with candidate S. aureus vaccines currently being evaluated in humans.

Objectives To determine whether the impact of a thoracic CT scan on community-acquired pneumonia (CAP) diagnosis and patient management varies according to emergency physician’s experience (≤10 vs >10 years). Methods Early thoracic CT Scan for Community-Acquired Pneumonia at the Emergency Department is an interventional study conducted from November 2011 to January 2013 in four French emergency departments, and included suspected patients with CAP. We analysed changes in emergency physician CAP diagnosis classification levels before and after CT scan; and their agreement with an adjudication committee. We performed univariate analysis to determine the factors associated with modifying the diagnosis classification level to be consistent with the radiologist’s CT scan interpretation. Results 319 suspected patients with CAP and 136 emergency physicians (75% less experienced with ≤10 years, 25% with >10 years of experience) were included. The percentage of patients whose classification was modified to become consistent with CT scan radiologist’s interpretation was higher among less-experienced than experienced emergency physicians (54.2% vs 40.2%; p=0.02). In univariate analysis, less emergency physician experience was the only factor associated with changing a classification to be consistent with the CT scan radiologist’s interpretation (OR 1.77, 95% CI 1.01 to 3.10, p=0.04). After CT scan, the agreement between emergency physicians and adjudication committee was moderate for less-experienced emergency physicians and slight for experienced emergency physicians (k=0.457 and k=0.196, respectively). After CT scan, less-experienced emergency physicians modified patient management significantly more than experienced emergency physicians (36.1% vs 21.7%, p=0.01). Conclusions In clinical practice, less-experienced emergency physicians were more likely to accurately modify their CAP diagnosis and patient management based on thoracic CT scan than more experienced emergency physicians. Trial registration number NCT01574066

In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin., Background Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers. Methods We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added. Results The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo. Conclusions DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments. Clinical Trials Registration NCT02176005.