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In older adults, prognostic performances of admission biomarkers have been poorly investigated. This study aims to compare the prognostic abilities of usual admission biomarkers, especially PCT and CRP, for major clinical outcomes, comparing older to younger adults diagnosed with an infection in the ED, and to investigate the prognostic abilities of PCT and CRP depending on the glomerular filtration rate (GFR).It was an observational, single-center, retrospective study, conducted in the Reims University Hospital, France. Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit.Over 1 year, 852 patients were included with 291 (34.2%) ≥75 years, and 127 (15.3%) patients had a GFR30 mL.minCaution must be taken when interpreting admission biomarkers, as their prognostic abilities are lower in older adults or in patients with renal insufficiency diagnosed with an infection.

Introduction: Understanding hypoxemia, with and without the clinical signs of acute respiratory failure (ARF) in COVID-19, is key for management. Hence, from a population of critical patients admitted to the emergency department (ED), we aimed to study silent hypoxemia (Phenotype I) in comparison to symptomatic hypoxemia with clinical signs of ARF (Phenotype II). Methods: This multicenter study was conducted between 1 March and 30 April 2020. Adult patients who were presented to the EDs of nine Great-Eastern French hospitals for confirmed severe or critical COVID-19, who were then directly admitted to the intensive care unit (ICU), were retrospectively included. Results: A total of 423 critical COVID-19 patients were included, out of whom 56.1% presented symptomatic hypoxemia with clinical signs of ARF, whereas 43.9% presented silent hypoxemia. Patients with clinical phenotype II were primarily intubated, initially, in the ED (46%, p < 0.001), whereas those with silent hypoxemia (56.5%, p < 0.001) were primarily intubated in the ICU. Initial univariate analysis revealed higher ICU mortality (29.2% versus 18.8%, p < 0.014) and in-hospital mortality (32.5% versus 18.8%, p < 0.002) in phenotype II. However, multivariate analysis showed no significant differences between the two phenotypes regarding mortality and hospital or ICU length of stay. Conclusions: Silent hypoxemia is explained by various mechanisms, most physiological and unspecific to COVID-19. Survival was found to be comparable in both phenotypes, with decreased survival in favor of Phenotype II. However, the spectrum of silent to symptomatic hypoxemia appears to include a continuum of disease progression, which can brutally evolve into fatal ARF.

(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000–1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024–3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286–4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.

Introduction Initial procalcitonin (PCT) levels may fail in mortality and septic shock prediction and raise cost-effectiveness issues. Since measurement of lactate, C-reactive protein (CRP), white blood cells and neutrophils is common in the emergency department (ED), we compared prediction abilities of these biomarkers to PCT. Methods From January 1st to December 31st, 2018, an observational, single center, retrospective study was conducted in the adult ED of the Reims University Hospital (France). Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. Results Over one year, 459 patients suspected with infection were included, of mean age 60.4 years (SD: 22.0), with 50.8% male, and 364 (79.3%) were hospitalized following ED visit. Overall, 45 (9.8%) patients had a bacteremia, 39 (8.5%) a septic shock and 54 (11.8%) died during their hospitalization. PCT and CRP showed the best discrimination for bacteremia, with an area under curve (AUC) of 0.68 for PCT and 0.65 for CRP. PCT and lactate showed similar good discriminative power for septic shock, with an AUC of 0.78 for both, and poor discrimination for in-hospital mortality, with an AUC of 0.62 for PCT and 0.69 for lactate. Systolic blood pressure and pulse oximetry showed similar discrimination for septic shock as PCT or lactate, while they showed higher discrimination for in-hospital mortality than PCT. Conclusion Usual admission biomarkers lack clinical utility in predicting septic shock or in-hospital mortality. CRP and PCT are poorly efficient in predicting bacteremia.

International audience; Procalcitonin (PCT) may be useful for early risk stratification in the emergency department (ED), but the transposition of published data to routine emergency practice is sometimes limited. An observational retrospective study was conducted in the adult ED of the Reims University Hospital (France). Over one year, 852 patients suspected of infection were included, of mean age 61.7 years (SD: 22.6), and 624 (73.2%) were hospitalized following ED visit. Overall, 82 (9.6%) patients died during their hospitalization with an odds ratio (OR) of 5.10 (95% CI: 2.19–11.87) for PCT ≥ 0.5, in multivariate logistic regression analyses. Moreover, 78 (9.2%) patients were admitted to an ICU, 74 (8.7%) had attributable bacteremia, and 56 (6.6%) evolved toward septic shock with an OR of 4.37 (2.08–9.16), 6.38 (2.67–15.24), and 6.38 (2.41–16.86), respectively, for PCT ≥ 0.5. The highest discriminatory values were found for patients with age

(1) Introduction: The neutrophil-to lymphocyte ratio is valued as a predictive marker in several inflammatory diseases. For example, an increasing NLR is a risk factor of mortality in sepsis. It also appears to be helpful in other settings such as cancer. The aim of our work was to study the prognostic value of NLR for disease severity and mortality in patients infected with SARS-CoV-2 upon their admission to the Emergency Department (ED) and its early variation (ΔNLR) in the first 24 h of management (H-24). (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective cohort study of patients with moderate or severe coronavirus disease 19 (COVID-19), who were all hospitalized after presenting to the ED. (3) Results: A total of 1035 patients were included in our study. Factors associated with infection severity were C-reactive protein level (OR: 1.007, CI 95%: [1.005–1.010], p &lt, 0.001), NLR at H-24 (OR: 1.117, CI 95%: [1.060–1.176], p &lt, 0.001), and ΔNLR (OR: 1.877, CI 95%: [1.160–3.036], p: 0.01). The best threshold of ΔNLR to predict the severity of infection was 0.222 (sensitivity 56.1%, specificity 68.3%). In multivariate analysis, the only biochemical factor significantly associated with mortality was again ΔNLR (OR: 2.142, CI 95%: ([1.132–4.056], p: 0.019). The best threshold of ΔNLR to predict mortality was 0.411 (sensitivity 53.3%, specificity 67.3%). (4) Conclusion: The NLR and its early variation (ΔNLR) could help physicians predict both severity and mortality associated with SARS-CoV-2 infection, hence contributing to optimized patient management (accurate triage and treatment).

International audience

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

Introduction: The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome. Methods: This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved. Results: We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60&ndash, 80%)). In the field, 77.7% (CI 95%: 71.8&ndash, 88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1&ndash, 56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8&ndash, 88.3% with a PaO2/FiO2 &lt, 200). In-hospital mortality was 33% (CI 95%: 24.6&ndash, 43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, p = 0.02, CT scan lesion extension &gt, 50%, OR = 0.76, p &lt, 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, p = 0.74). Conclusion: The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.

International audience; To evaluate the relevance of ceftriaxone prescriptions in an emergency department of a university hospital and suggest whenever possible an antibiotic alternative with a lower ecological impact. All ceftriaxone prescriptions in the first complete week of each month during the year 2016, in the emergency department of the Grenoble university hospital, have been analyzed by an IDS referent in antibiotic prescriptions. Ceftriaxone prescription was considered appropriate if justified (an antibiotic must be used), relevant (ceftriaxone is a good choice), and adapted (in terms of dose, route, and period of administration), regardless of a potential antibiotic association, consistent with international recommendations. We considered patient outcome regarding the quality of initial prescription. Additionally, alternatives were suggested for relevant prescriptions. We included 327 patients, of which ceftriaxone prescriptions were not appropriate in 37.6% of cases: 13.5% were not justified, 12.8% not relevant, and 11.3% not adapted. The main factors associated with unjustified prescriptions were urinary, dermatological, and less frequent infection sites (p

Introduction Emergency departments play a key role in the diagnosis and treatment of transient ischemic attacks, but limited data are available about the early management of such patients in emergency wards. Therefore, we aimed to evaluate emergency physicians’ management of transient ischemic attack and analyze variations factors. Methods A multicenter survey among emergency physicians of the Grand Est region network (Est-RESCUE) was conducted from January 28th to March 28th, 2019. Medical and administrative data were collected by the same network and the national directory of medical resources. Results Among 542 emergency physicians recipients, 78 answered (14%) and 71 were finally included, practicing in 25 public hospitals homogeneously distributed across the territory, including 3 university hospitals. A cerebral magnetic resonance imaging was obtained for 75%-100% of patients by 4.3% of responders, 36.4% of which were performed within more than 24 hours. A cardiac monitoring was prescribed in 75%-100% of cases by 32.4% of responders. A neurologic consultation was routinely requested by 84.6% of responders practicing in a university hospital and 36.8% of responders practicing in a community hospital (P = .02). Patients were hospitalized in a neurovascular unit in 75%-100% of cases by 17.4% of responders, which happened more likely in university hospitals (P Conclusions Transient ischemic attack suffers from management disparities across territories, due to limited access to technical facilities and neurologic consultations. Therefore, international recommendations are too often not followed. Implementation of territorial neurovascular tracks may help to standardize the management of these patients.

© 2015 by the American Thoracic Society. Rationale: Microvesicles (MVs) are anuclear fragments of cells released from the endosomal compartment or shed from surface membranes. We and other investigators demonstrated that MVs released by mesenchymal stem cells (MSCs) were as effective as the cells themselves in inflammatory injuries, such as after endotoxininduced acute lung injury. However, the therapeutic effects of MVs in an infectious model of acute lung injury remain unknown. Objectives: We investigated the effects of human MSC MVs on lung inflammation, protein permeability, bacterial clearance, and survival after severe bacterial pneumonia. Methods: We tested the effects of MVs derived from human MSCs on Escherichia coli pneumonia in mice. We also studied the interactions between MVs and human monocytes and human alveolar epithelial type 2 cells. Measurements and Main Results: Administration of MVs derived from human MSCs improved survival in part through keratinocyte growth factor secretion and decreased the influx of inflammatory cells, cytokines, protein, and bacteria in mice injured with bacterial pneumonia. In primary cultures of human monocytes or alveolar type 2 cells, the uptake of MVs was mediated by CD44 receptors, which were essential for the therapeutic effects. MVs enhanced monocyte phagocytosis of bacteria while decreasing inflammatory cytokine secretion and increased intracellular ATP levels in injured alveolar epithelial type 2 cells. Prestimulation of MSCs with a toll-like receptor 3 agonist further enhanced the therapeutic effects of the released MVs. Conclusions: MVs derived from human MSCs were as effective as the parent stem cells in severe bacterial pneumonia.

Mesenchymal stem cells (MSCs) can be derived from multiple tissue sources. However, the optimal source of MSCs for cell-based therapy for acute lung injury (ALI) is unclear. In the present experiments, we studied bone marrow (BM)-derived and embryonic stem cell-derived human MSC (ES-MSCs) as a therapeutic agent in Escherichia coli endotoxin-induced ALI in mice. We hypothesized that ES-MSCs would be more potent than BM-MSCs owing to its more primitive source of origin. ALI was induced by the intratracheal instillation of endotoxin at 4 mg/kg into 10–12-week-old C57BL/6 mice with or without BM-MSCs, ES-MSCs, or normal human lung fibroblasts as a cellular control. Compared with the endotoxin-injured mice at 48 hours, the administration of ES-MSCs provided results similar to those of BM-MSCs, significantly reducing the influx of white blood cells and neutrophils and decreasing the secretion of the inflammatory cytokines, macrophage inflammatory protein-2 and tumor necrosis factor-α, in the injured alveolus. BM-MSCs also reduced extravascular lung water, a measure of pulmonary edema, by 60% and the total protein levels, a measure of lung permeability, by 66%. However, surprisingly, ES-MSCs did not have these protective effects, which was partially explained by the increased secretion of matrix metallopeptidase 9 by ES-MSCs, an enzyme known to increase lung protein permeability. In conclusion, both BM-MSCs and ES-MSCs markedly decreased endotoxin-induced inflammation. However, ES-MSCs did not show any beneficial effect on reducing pulmonary edema and lung protein permeability compared with BM-MSCs, suggesting that not all MSCs behave in a similar fashion. Our results highlight the need perhaps for a disease-specific potency assay for MSCs. Significance To determine the optimal source of mesenchymal stem cells (MSCs) for cell-based therapy for acute lung injury, bone marrow (BM)- and embryonic stem cell-derived human MSC (ES-MSCs) were compared as therapeutic agents for Escherichia coli endotoxin-induced lung injury in mice. ES-MSCs behaved similarly to BM-MSCs by markedly decreasing the inflammatory response induced by endotoxin. However, unlike BM-MSCs, ES-MSCs provided no protective effects against increasing lung water and protein permeability, in part because of an increase in expression of matrix metallopeptidase 9 by ES-MSCs. In patients with acute respiratory distress syndrome, impaired alveolar fluid clearance (i.e., no resolution of pulmonary edema fluid) has been associated with higher mortality rates. Although ES-MSCs might ultimately be found to have properties superior to those of BM-MSCs, such as for immunomodulation, these results highlight the need for a disease-specific potency assay for stem cell-based therapy.

Measurement of exhaled carbon monoxide (eCO) might help in the selection of lung grafts during ex vivo lung perfusion (EVLP) since its endogenous production is increased under ischemia reperfusion. The objective of this study was to measure eCO variations depending on the extent of lung ischemia reperfusion injuries. Using a porcine model and a laser spectrometer instrument, eCO was measured during EVLP. eCO was compared after 30 min (D0) or 24 h (D1) of cold ischemia. The ability of eCO to distinguish lungs deemed suitable for transplantation was evaluated. Six lungs were studied at D0 and compared to six lungs studied at D1. eCO was systematically higher on D1 (1.35 ± 0.26 ppmv versus 0.95 ± 0.31 ppmv, p = 0.01). The best threshold concentration for eCO to select lungs was 0.86 ppmv (area under the receiver operating characteristic curve: 0.65 [95% confidence interval: 0.34-0.97], p = 0.40). These results show that eCO varies during EVLP. The interpretation of this variation and the role of eCO as a biomarker of ischemia reperfusion injuries during EVLP should be tested in further clinical studies.

Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver, or brain. Genomic, proteomic, and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of promitotic, antiapoptotic, antiinflammatory, and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, the authors review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. (Anesthesiology 2014; 121:1099-121)

International audience; Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising from the first hours after transplantation.The first etiology of the primary graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important morbi-mortality.Lung ischemia-reperfusion increases the oxidative stress, inactivates the sodium pump, increases the intracellular calcium, leads to cellular death and the liberation of pro-inflammatory mediators.Researches relative to the reduction of the lung ischemia-reperfusion injuries are numerous but few of them found a place in common clinical practice, because of an insufficient level of proofs.Ex vivolung evaluation is a suitable technique in order to evaluate therapeutics supposed to limit lung ischemia-reperfusion injuries.

Introduction : La meningite bacterienne est une urgence diagnostique et therapeutique grevee d'une importante morbi-mortalite. Notre objectif principal etait d'evaluer la prise en charge des suspicions de meningites dans un service d'accueil des urgences (SAU) les mois suivants l'actualisation des recommandations. Materiel et methode : Il s'agissait d'une etude retrospective observationnelle realisee entre le 1er janvier et le 30 juin 2009 au SAU du CHU de Grenoble. Ont ete inclus 68 patients de plus de 15 ans et trois mois, suspects de meningite (fievre dans les 24 heures precedent l'admission accompagnee d'au moins un signe meninge ou neurologique) et beneficiant d'une ponction lombaire (PL) dans les 48 heures suivant leur admission. Deux infectiologues independants ont evalue les prises en charge, apres lecture du dossier medical des urgences, des resultats biologiques et du compte-rendu final d'hospitalisation. Resultats : Le delai median de realisation de la PL etait de 5,5 heures [3,7-8,9], celui d'administration des antibiotiques de 6 heures [3,3-8,75]. La prescription de lactates etait stable au cours des 6 mois d'etude (p=0.58) ; celle de procalcitonine augmentait de maniere significative (p=0,02). La realisation d'un scanner avant la PL augmentait nettement le delai de prelevement du LCR (p < 0,001), sans toutefois impacter sur les delais de prescription et d'administration des antibiotiques. Pour les patients atteints de meningite bacterienne, le choix des molecules, posologies et voies d'administration, les delais de realisation de la PL et d'administration des antibiotiques, etaient estimes conformes. Conclusion : Nos delais de prise en charge sont proches de ceux retrouves dans la litterature. Neanmoins, nous devons chercher a les reduire conformement a la Conference de consensus. Cela implique tous les acteurs de soins, la formation des personnels et la realisation de protocoles (prise en charge therapeutique, indication de scanner avant ponction lombaire).

International audience; Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140 mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein

L’encephalite limbique est une affection rare, mal connue mais qui semble sous estimee et qui doit etre evoquee devant une triade diagnostique classique mais peu specifique. Cette pathologie auto-immune se caracterise par des troubles mnesiques, psychiatriques et neurologiques a type de crises convulsives. Le diagnostic n’est souvent etabli qu’au terme d’une hospitalisation prolongee. Nous rapportons l’observation detaillee de deux cas d’encephalites limbiques diagnostiquees chez de jeunes patients sans antecedent, initialement admis aux urgences pour une symptomatologie psychiatrique brutale et bruyante ayant entrainee une hospitalisation inappropriee en secteur specialise. Ces deux cas rapportes nous permettent d’apprehender toute la difficulte diagnostique de cette pathologie mais aussi la difficulte de triage et d’orientation, specifique a la medecine d’urgence.

Resume Objectif Les buts de notre etude etaient de caracteriser l’activite d’une consultation mobile d’infectiologie (CMI) dans un CHU et d’explorer l’adhesion des praticiens aux avis donnes par les infectiologues. Patients et methodes Toutes les demandes recues par la CMI pour un premier avis ainsi que les reponses apportees etaient colligees de facon exhaustive sur une periode d’un mois. Les avis donnes pour des patients hospitalises au CHU faisaient l’objet d’un suivi a 72 heures afin d’evaluer l’observance des avis. Resultats Six cents dix-neuf demandes ont ete enregistrees : 47 % provenaient du CHU et 53 % de l’exterieur. Les demandes internes emanaient principalement des services de chirurgie (47 %) et de medecine aigue (41 %). La plupart d’entre elles (92 %) concernaient le traitement d’une infection ou une aide au diagnostic. Les demandes externes provenaient principalement de medecins (85 %) exercant en ambulatoire ou en etablissement de sante. Elles concernaient en premier lieu la prophylaxie (47 %) et le traitement d’une infection ou une aide au diagnostic (43 %). Parmi les 176 avis demandes pour des patients hospitalises au CHU, 87 % etaient parfaitement suivis. Les avis etaient mieux suivis lorsqu’ils etaient delivres par un infectiologue senior (p = 0,02) ou par telephone (p = 0,03) et moins bien suivis pour les patients presentant une pathologie nosocomiale (p = 0,03). Conclusion La CMI rend un important service a la communaute medicale et ses recommandations sont en general bien suivies. Les consultations « informelles » representent une part importante de son activite.

Resume Objectif Evaluer la pertinence et la conformite des prescriptions antibiotiques dans un service d’accueil des urgences (SAU) medicochirurgicales, et etudier les facteurs susceptibles de les influencer. Methodes Cette etude prospective concernait tous les patients âges de plus de 15 ans et 3 mois examines au SAU sur une periode de 100 jours et pour lesquels une antibiotherapie etait instauree. La pertinence des indications et la conformite des prescriptions aux regles d’utilisation etaient evaluees par 2 infectiologues independants. L’etude s’interessait egalement a l’evolution des patients a 7 jours de l’initiation de l’antibiotherapie, a leur duree d’hospitalisation et aux eventuelles modifications therapeutiques. Resultats Deux cent onze patients ont ete inclus, dont 47 % d’hommes. Les prescriptions etaient jugees pertinentes dans 53 % des cas et a la fois pertinentes et conformes dans leur realisation pour 34 % des cas. Cinquante pour cent des prescriptions concernaient des pathologies urinaires ou pulmonaires. Quatre familles d’antibiotiques correspondaient a 88 % des prescriptions. Les erreurs de prescriptions etaient liees a l’utilisation excessive de bitherapies, de traitements intraveineux et a des erreurs de spectre. Cinquante-six pour cent des patients etaient secondairement hospitalises, generalement plus d’une semaine (70 % des cas). En cas de non-hospitalisation, 31 % des patients avaient des durees de traitement a domicile inadaptees. Quarante-quatre pour cent des antibiotherapies initiees au SAU etaient secondairement modifiees. Conclusion Un travail multidisciplinaire parait indispensable afin d’optimiser les prescriptions antibiotiques.

To evaluate the effects of 1 and 5 μM of Cyclosporine A (CsA), administered 24 hours after a cold ischemic period, in an ex vivo reperfused pig lung model.The experiments were performed in 15 pigs. Each pair of lungs was surgically separated. Extracorporeal perfusion and mechanical ventilation were started after a cold ischemia of 2 hours for one lung and 24 hours for the contralateral. We constituted three groups (n = 5 each): two groups for which the lung underwent a 24-hour ischemia received either 1 or 5 μM of CsA at the time of reperfusion, and a control group without CsA. For each group, lungs undergoing a 2-hour ischemia did not receive CsA.Reperfusion with either CsA increased the PO2 levels in a dose dependent manner, and reduced concentrations of the receptor for advanced glycation endproducts, compared to the control. The pulmonary arterial pressure, the capillary pressure, and the pulmonary vascular resistances were not increased, even with 5 μM of CsA. No significant change was shown on cytokines levels.Postconditioning with CsA improves lung function, after a 24-hour cold ischemic period. Either 1 or 5 μM seemed to be safe regarding the pulmonary vascular pressures and resistances.

This review proposes an update of the state of the art and the ongoing clinical trials of ex vivo lung perfusion for lung transplantation in patients. Ex vivo lung perfusion techniques (EVLP) can be used to evaluate a lung graft outside of the body. The goal of EVLP is to study the functional status of lung grafts that were first rejected for transplantation because they did not match all criteria for a conventional transplantation. After an EVLP evaluation, some of these lungs may be requalified for a possible transplantation in patients. This article proposes an overview of the developments of EVLP techniques. During EVLP, the perfusion and ventilation of the isolated lung preparation are very progressive in order to avoid oedema due to ischaemia-reperfusion injuries. Lung evaluation is mainly based on gasometric (PaO2/FiO2) and rheological criteria (low pulmonary arterial resistance). Several series of patients transplanted with EVLP evaluated lungs have been recently published with promising results. EVLP preparations also allow a better understanding of the physiopathology and treatments of ischaemia-reperfusion injuries. Organ procurements from "non-heart-beating" donors will probably require a wider application of these ex vivo techniques. The development of semi-automated systems might facilitate the clinical use of EVLP techniques.

Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.

The need to increase the donor pool for lung transplantation is a major public health issue. We previously found that administration of mesenchymal stem cells "rehabilitated" marginal donor lungs rejected for transplantation using ex vivo lung perfusion. However, the use of stem cells has some inherent limitation such as the potential for tumor formation. In the current study, we hypothesized that microvesicles, small anuclear membrane fragments constitutively released from mesenchymal stem cells, may be a good alternative to using stem cells. Using our well established ex vivo lung perfusion model, microvesicles derived from human mesenchymal stem cells increased alveolar fluid clearance (i.e. ability to absorb pulmonary edema fluid) in a dose-dependent manner, decreased lung weight gain following perfusion and ventilation, and improved airway and hemodynamic parameters compared to perfusion alone. Microvesicles derived from normal human lung fibroblasts as a control had no effect. Co-administration of microvesicles with anti-CD44 antibody attenuated these effects, suggesting a key role of the CD44 receptor in the internalization of the microvesicles into the injured host cell and its effect. In summary, microvesicles derived from human mesenchymal stem cells were as effective as the parent mesenchymal stem cells in rehabilitating marginal donor human lungs.

La prise en charge d’une crise convulsive fait partie du quotidien de l’urgentiste. Pour autant, ce cadre nosologique regroupe de nombreuses etiologies dont les frequences sont tres variables selon les continents. Notre observation releve le fait que le diagnostic etiologique et la prise en charge therapeutique des voyageurs et des migrants doivent imperativement tenir compte des particularites ecologiques de chaque pays.

Resume Cette observation rapporte le cas d’une intoxication medicamenteuse aigue volontaire chez une femme de 24 ans, initialement annoncee comme une mono-intoxication a la venlafaxine. Son interet releve de l’analyse du deroulement des etapes qui ont conduit au diagnostic, en particulier l’anamnese, le diagnostic du syndrome toxicologique et l’identification des toxiques. Elle montre les difficultes d’etablir aux urgences un diagnostic de certitude et un diagnostic de gravite.

Objective Several works highlight the role of CsA in the prevention of IRI, but none focus on isolated lungs. Our objective was to evaluate the effects of CsA on IRI on ex vivo reperfused pig lungs. Methods Thirty-two pairs of pig lungs were collected and stored for 30 minutes at 4°C. The study was performed in four groups. First, a control group and then three groups receiving different concentrations of CsA (1, 10, and 30 μM) at two different times: once at the moment of lung procurement and another during the reperfusion procedure. The ex vivo lung preparation was set up using an extracorporeal perfusion circuit. Gas exchange parameters, pulmonary hemodynamics, and biological markers of lung injury were collected for the evaluation. Results CsA improved the PaO2/FiO2 ratio, but it also increased PAP, Pcap, and pulmonary vascular resistances with dose-dependent effects. Lungs treated with high doses of CsA displayed higher capillary-alveolar permeability to proteins, lower AFC capacities, and elevated concentrations of pro-inflammatory cytokines. Conclusions These data suggest a possible deleterious imbalance between the beneficial cell properties of CsA in IRI and its hemodynamic effects on microvascularization.

Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising from the first hours after transplantation. The first etiology of the primary graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important morbi-mortality. Lung ischemia-reperfusion increases the oxidative stress, inactivates the sodium pump, increases the intracellular calcium, leads to cellular death and the liberation of pro-inflammatory mediators. Researches relative to the reduction of the lung ischemia-reperfusion injuries are numerous but few of them found a place in common clinical practice, because of an insufficient level of proofs. Ex vivolung evaluation is a suitable technique in order to evaluate therapeutics supposed to limit lung ischemia-reperfusion injuries.

Ischemia-reperfusion injuries are a critical determinant of lung transplantation success. The endogenous production of carbon monoxide (CO) is triggered by ischemia-reperfusion injuries. Our aim was, therefore, to assess the feasibility of exhaled CO measurements during the ex vivo evaluation of lungs submitted to ischemia-reperfusion injuries. Five pigs were euthanized and their lungs removed after pneumoplegia. After cold storage (30 min, 4°C), the lungs were connected to an extracorporeal membrane oxygenation circuit, slowly warmed-up, and ventilated. At the end of a 45-min steady state, CO measurements were performed by optical-feedback cavity-enhanced absorption spectroscopy, a specific laser-based technique for noninvasive and real-time low gas concentration measurements. Exhaled CO concentration from isolated lungs reached 0.45±0.19 ppmv and was above CO concentration in ambient air and in medical gas. CO variations peaked during the expiratory phase. Changes in CO concentration in ambient air did not alter CO concentrations in isolated lungs. Exhaled CO level was also found to be uncorrelated to heme oxygenase (HO-1) gene expression. These results confirm the feasibility of accurate and real-time CO measurement in isolated lungs. The presented technology could help establishing the exhaled CO concentration as a biomarker of ischemia-reperfusion injury in ex vivo lung perfusion.

Bacterial meningitis is a diagnosis and therapeutic emergency. It is associated with high morbidity and mortality. The objective was to evaluate the management of suspicion of meningitis in an emergency unit, following the update of recommendations.A retrospective observational study was conducted between 1st January and 30th June 2009 in the emergency unit of Grenoble University Hospital. Inclusion criteria were: patient aged 15 years and 3 months or older with suspicion of meningitis (fever in the last 24 hours with the presence of at least one meningeal or neurological clinical sign), for whom a lombar puncture was realized in the 48 hours following the admission. Two infectious disease specialists independently evaluated the management of these patients in the emergency unit.Sixty-eight patients were included. Median time of the lombar puncture was 5.5 hours after admission [25-75 percentiles, 3.7-8,9]. Median time for antibiotic administration was 6 hours after admission [25-75 percentiles, 3.3-8.75]. Lactate prescription was stable during the study period (P=0.58) whereas procalcitonin prescription increased significantly (P=0.02). The realization of a brain scanner before the lumbar puncture was associated with a significant delay in the realization of the lumbar puncture (P0.001), and was not associated with a delay in the prescription and administration of antimicrobial treatment. According to the infectious disease specialists, an antimicrobial treatment was recommended for 37 patients (54.4%); and 35 of them (94.6%) received an antibiotic in the emergency department. Dosage of ceftriaxone complied with recommendations in 17.8% of cases. A brain scanner was recommended for 33 patients and realized for 25 among them (75.8%). Ten patients (28.6%) had a brain scanner whereas it was not recommended.Time management was in accordance with those found in previous studies, although higher than those recommended. Consequently it should be reduced. All professionals should be concerned. Staff training and writing of protocols are necessary (especially for the treatment and the brain scanner indications).

Infectious diseases (ID) make up a substantial part of a general practitioner's (GP's) workload. GPs frequently solicit ID specialists requesting advice on managing their patients with ID. The objectives of this study were to examine GP reasons for soliciting ID consultations and to assess the GPs' and specialists' opinions of the ID consultation service.This was a prospective study of consecutive solicited ID consultations requested by GPs from the ID specialists of a 2200-bed university-affiliated hospital, conducted between October 2008 and March 2009. Data related to GP characteristics, their reasons for requesting the consultation, the recommendations given by the specialists, and the specialists' perceptions of the exchange were collected. GPs were asked to report their adherence to recommendations and their perceptions of the consultations.A mean of 57 telephone consultations per month were requested by GPs during the study period. ID specialist recommendations were related to antibiotic treatment (66.2%), diagnostic or monitoring tests (46.5%), and a subsequent formal consultation or hospitalization (29.6%). The reasons reported for GPs requesting an ID consultation were related to patient management (96.5%), rapidity of access (86.3%), and quality of care improvement (84.2%). GPs were satisfied with the telephone consultations in 97.9% of cases and ID specialists in 94.7%.Telephone consultations with ID specialists were widely appreciated by GPs, probably due to the accessibility of these specialists. Further study is needed to assess the effects of these telephone consultations on quality of care.

Background Solicited consultations constitute a substantial workload for infectious disease (ID) specialists in the hospital setting. The objectives of this survey were to describe requesting physicians' experiences regarding ID consultations. Methods A cross-sectional survey was conducted in a university-affiliated hospital in France in 2009. All physicians were eligible (n = 530) and received a self-administered questionnaire. The main outcomes were reasons for request and opinion. Secondary outcomes were frequency of request and declared adherence to recommendations. Results The participation rate was 44.7% (237/530). Among the responders, 187 (79%) had solicited the ID consultation service within the previous year. Ninety-three percent of the responders (173/187) were satisfied with the ID consultation. The main reasons for requesting consultations were the need for therapeutic advice (93%), quality of care improvement (73%) and the rapidity of access (61%). ID consultations were requested several times a month by 52% (72/138) of senior physicians and by 73% (36/49) of residents (p = 0.01). Self-reported adherence to diagnostic and therapeutic recommendations was 83% and 79%, respectively. Conclusion The respondent requesting physicians expressed great satisfaction regarding ID consultations that they requested principally to improve patient care and to assist in medical decision making.

International audience; The purpose of this study was to compare compliance with recommendations and clinical outcomes between formal and informal infectious disease specialist consultations. Six hundred twenty-seven consecutive adult inpatients who received an infectious disease consultation in a university-affiliated hospital were included. After adjusting for quintile of propensity score, we compared compliance with the consultant's recommendations and clinical outcomes for 443 (70.7%) and 184 (29.3%) formal and informal consultations. Informal and formal consultations were associated with comparable levels of compliance with recommendations for antimicrobial treatment (86.5% vs 88.9%; adjusted odds ratio [aOR], 0.63; 95% confidence interval, 0.34-1.14; P = 0.13) and diagnostic or monitoring tests (72.6% vs 72.0%; aOR, 0.91 [0.53-1.57]; P = 0.73). The rates of early clinical improvement (58.2% vs 58.6%; aOR, 1.11 [0.70-1.74]; P = 0.66), subsequent consultation (34.2% vs 36.3%; aOR, 0.80 [0.53-1.21]; P = 0.29), in-hospital mortality (4.9% vs 8.4%; aOR, 0.55 [0.24-1.24]; P = 0.15), and the median length of stay (23 vs 20 days; aOR of discharge, 0.90 [0.74-1.10]; P = 0.30) did not differ depending on the type of consultation. This study provides observational evidence that informal consultations result in levels of compliance with recommendations comparable to formal consultations, without compromising patient safety. Further study is needed to refine the criteria for requesting or providing informal rather than formal consultations.

To respond to the increasing requests of non-infectious disease physicians for access to infectious diseases expertise, a hotline was created in the infectious diseases consultation (IDC) unit of the Grenoble university-affiliated hospital (GUH). This study describes the patterns of solicited consultations provided by the hotline during a 1-year period. We conducted a prospective study of consecutive solicited IDCs requested by physicians in 2008. A total of 7,863 consultations were requested by physicians over 1 year; 4,407 (56.0%) by ambulatory physicians, 2,933 (37.3%) by GUH physicians, and 523 (6.7%) by physicians in public or private hospitals. The majority of consultations were requested via cell phone (58.7%). The main reasons for requesting a consultation were related to antimicrobial treatment for hospital-based physicians and prophylaxis for ambulatory physicians (p < 0.001). Recommendations to perform diagnostic or monitoring tests were less frequent in ambulatory medicine (16%) than in the GUH (59%) or other hospitals (63%, p < 0.001). The route of consultation for patients with nosocomial infections was more likely to be formal (p < 0.001). The activity of the IDC hotline attests to an important need for such expertise consultation, both in hospitals and in ambulatory medicine.

International audience; BACKGROUND: The ocular manifestations of syphilis are protean and can affect every structure of the eye. There has been a recent increase of syphilis infection in Europe. We report recent cases of ocular syphilis infection in a tertiary center. METHODS: During a 2.5-year period (2005-2007) we collected the medical records of eight male patients with ocular syphilis. The diagnosis was based on serological tests on blood samples and cerebrospinal fluid. All patients underwent a check-up to rule out another etiological diagnosis and to detect the presence of any other sexually transmitted infections. RESULTS: The ocular lesions included: chorioretinitis (one case), retinitis (two cases), panuveitis with macular edema (two cases), episcleritis (one case), anterior optic neuritis (one case), and retrobulbar optic neuropathy (one case). Infection of the cerebrospinal fluid was detected in three of the five patients tested. In six cases, the inflammation was unilateral, and the anatomical and functional prognosis was excellent at the 6-month follow-up visit. Co-infection with human immunodeficiency virus was reported in five patients, with a CD4 T lymphocyte count greater than 300/mm(3). Most of the patients were treated with parenteral ceftriaxone (1 g daily) for 3 weeks with good tolerance. One patient was treated with intravenous penicillin G (18 MUI daily). Only one patient with anterior optic neuritis required systemic steroid therapy associated with antibiotics. Sequelae included sectorial atrophy of the optic nerve with visual field loss (n = 1) and abnormalities of the retinal pigment epithelium (n = 3). CONCLUSIONS: All patients with ocular syphilis exhibited functional improvement and resolution of ocular inflammation after a specific antibiotic treatment. As a great imitator, syphilis should be considered in all patients with uveitis, scleritis, episcleritis, or optic neuritis, especially in men with high-risk sexual behavior.

International audience; OBJECTIVES: Solicited consultations constitute a substantial workload for infectious disease specialists (IDSs). The impact of physician adherence to recommendations on clinical outcomes following solicited IDS consultations has not been previously studied. The objectives of the study were to identify the factors associated with adherence and to determine whether adherence to recommendations was associated with better clinical outcomes. METHODS: A prospective study was conducted on 621 patients, aged > or = 18 years, hospitalized in a university-affiliated hospital in France, who received an IDS consultation between December 2007 and June 2008. The main outcome was early clinical improvement, and the secondary outcomes were length of stay and in-hospital mortality. RESULTS: Adherence to the IDS's recommendations was 88.2% (548/621) for antimicrobial treatment and 72.2% (317/439) for diagnostic or monitoring tests. In a multivariable analysis, independent factors of adherence to therapeutic recommendations were a community-acquired infection [adjusted odds ratio (OR), 1.8; 95% confidence interval (CI), 1.1-3.0] and discontinuation or non-use of antibiotic treatment (adjusted OR, 9.7; 95% CI, 1.2-80.3). Adherence to recommendations for antibiotic treatment was associated with a higher rate of early clinical improvement (60.7% versus 43.9%, P = 0.01), shorter median length of stay (20 days versus 23 days, P = 0.03) and comparable in-hospital mortality (7.7% versus 5.5%, P = 0.50). CONCLUSIONS: Factors associated with non-adherence must be anticipated by IDSs during consultations, because non-adherence leads to worse clinical outcomes. Further studies are needed to identify the interventions that could improve physician adherence to recommendations made during solicited consultations.

To study the appropriateness and conformity to antibiotic prescription guidelines in an emergency department and to assess the factors likely to influence them.This prospective study included all adult patients visiting the emergency department over a period of 100 days and receiving antibiotic treatment. Two independent specialists in infectious disease assessed the appropriateness of the indications and the treatment's conformity with good practice guidelines. We also studied patient's status 7 days after initiation of antibiotic treatment, duration of hospitalization and any treatment changes.The study included 211 patients, 47% of them men. Prescriptions were appropriate in 53% of cases and in accordance with guidelines in 34%. Half of all prescriptions were related to urinary tract or pulmonary infections. Four antibiotic families accounted for 88% of prescriptions. Prescription errors were related to multidrug treatments, intravenous drugs, and inappropriate antibiotic families. More than half (56%) of the patients were admitted, and 70% of these remained in the hospital more than one week. Duration of treatment was inappropriate for 31% of the patients not admitted. In all, 44% of the antibiotic prescriptions ordered in the emergency department were later modified.Multidisciplinary work is essential in improving the quality of antibiotic prescriptions in an emergency department.