Publications by authors named "Laurent Muller"

162 Publications

Pneumothorax diagnosis with lung sliding quantification by speckle tracking: A prospective multicentric observational study.

Am J Emerg Med 2021 May 11;49:14-17. Epub 2021 May 11.

Montpellier university, EA 2992 IMAGINE, Department of Anesthesiology, Emergency and Critical Care Medicine, Intensive Care Unit, Nîmes University Hospital, Nîmes, France. Electronic address:

Introduction: Lung ultrasound is commonly used for the diagnosis of pneumothorax. However, recognition of pleural sliding is subjective and can be difficult for novice. The primary objective was to compare a novices physician's performance in diagnosing pneumothorax from ultrasound (US) scans either with visual evaluation or with maximum longitudinal pleural strain (MLPS). The secondary objective was to compare the diagnostic relevance of US with visual evaluation or MLPS to diagnose pneumothorax with an intermediately experienced and an expert physician.

Methods: We conducted a prospective, observational study in two emergency department and two intensive care unit, between February 2019 and June 2020. We included 99 adult patients with suspected pneumothorax, who received a chest computed tomography (CT). Three physicians with different experience of interpreting US scans (a novice physician, an intermediately experienced physician, and an expert) analyzed the US scans of 99 patients with suspected pneumothorax (50 (51%) with confirmed pneumothorax), which were confirmed by CT scan.

Results: With a threshold of 5%, the MLPS sensitivity was 94% (95% CI [83%; 98%]), and the specificity was 100% (95% CI [93%; 100%]). The novice physician had an area under the curve (AUC) with visual analysis of 0.75 (95% CI [0.67; 0.83]) vs 0.86 (95% CI [0.79; 0.94]) with MLPS (p = 0.04). The intermediate physician's AUC for diagnosing pneumothorax with visual analysis was 0.93 (95% CI [0.88; 0.99]) vs 1.00 (95% CI [1.00; 1.00]) with MLPS (p < 0.01) and for the expert physician it was 0.98 (95% CI [0.95;1.00]) vs 0.97 (95% CI [0.93; 1.00]), respectively (p = 0.69).

Conclusion: In our study, speckle tracking analysis improved the accuracy of US for the novice and the intermediate but not the expert sonographer in the diagnosis of pneumothorax.
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http://dx.doi.org/10.1016/j.ajem.2021.05.022DOI Listing
May 2021

Effect of the use of an endotracheal tube and stylet versus an endotracheal tube alone on first-attempt intubation success: a multicentre, randomised clinical trial in 999 patients.

Intensive Care Med 2021 Jun 25;47(6):653-664. Epub 2021 May 25.

Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, PhyMedExp, INSERM U1046, CNRS UMR, 9214, Montpellier Cedex 5, France.

Purpose: The effect of the routine use of a stylet during tracheal intubation on first-attempt intubation success is unclear. We hypothesised that the first-attempt intubation success rate would be higher with tracheal tube + stylet than with tracheal tube alone.

Methods: In this multicentre randomised controlled trial, conducted in 32 intensive care units, we randomly assigned patients to tracheal tube + stylet or tracheal tube alone (i.e. without stylet). The primary outcome was the proportion of patients with first-attempt intubation success. The secondary outcome was the proportion of patients with complications related to tracheal intubation. Serious adverse events, i.e., traumatic injuries related to tracheal intubation, were evaluated.

Results: A total of 999 patients were included in the modified intention-to-treat analysis: 501 (50%) to tracheal tube + stylet and 498 (50%) to tracheal tube alone. First-attempt intubation success occurred in 392 patients (78.2%) in the tracheal tube + stylet group and in 356 (71.5%) in the tracheal tube alone group (absolute risk difference, 6.7; 95%CI 1.4-12.1; relative risk, 1.10; 95%CI 1.02-1.18; P = 0.01). A total of 194 patients (38.7%) in the tracheal tube + stylet group had complications related to tracheal intubation, as compared with 200 patients (40.2%) in the tracheal tube alone group (absolute risk difference, - 1.5; 95%CI - 7.5 to 4.6; relative risk, 0.96; 95%CI 0.83-1.12; P = 0.64). The incidence of serious adverse events was 4.0% and 3.6%, respectively (absolute risk difference, 0.4; 95%CI, - 2.0 to 2.8; relative risk, 1.10; 95%CI 0.59-2.06. P = 0.76).

Conclusions: Among critically ill adults undergoing tracheal intubation, using a stylet improves first-attempt intubation success.
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http://dx.doi.org/10.1007/s00134-021-06417-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144872PMC
June 2021

Can Thoracic Ultrasound on Admission Predict the Outcome of Critically Ill Patients with SARS-CoV-2? A French Multi-Centric Ancillary Retrospective Study.

Adv Ther 2021 05 14;38(5):2599-2612. Epub 2021 Apr 14.

Department of Anesthesiology and Intensive Care Unit, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Nord Hospital, Marseille, France.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks have led to massive admissions to intensive care units (ICUs). An ultrasound examination of the thorax is widely performed on admission in these patients. The primary objective of our study was to assess the performance of the lung ultrasound score (LUS) on ICU admission to predict the 28-day mortality rate in patients with SARS-CoV-2. The secondary objective was to asses the performance of thoracic ultrasound and biological markers of cardiac injury to predict mortality.

Methods: This multicentre, retrospective, observational study was conducted in six ICUs of four university hospitals in France from 15 March to 3 May 2020. Patients admitted to ICUs because of SARS-CoV-2-related acute respiratory failure and those who received an LUS examination at admission were included. The area under the receiver-operating characteristics (ROC) curve was determined for the LUS score to predict the 28-day mortality rate. The same analysis was performed for the Simplified Acute Physiology Score, left ventricular ejection fraction, cardiac output, brain natriuretic peptide and ultra-sensitive troponin levels at admission.

Results: In 57 patients, the 28-day mortality rate was 21%. The area under the ROC curve of the LUS score value on ICU admission was 0.68 [95% CI 0.54-0.82; p = 0.05]. In non-intubated patients on ICU admission (n = 40), the area under the ROC curves was 0.84 [95% CI 0.70-0.97; p = 0.005]. The best cut-off of 22 corresponded to 85% specificity and 83% sensitivity.

Conclusions: LUS scores on ICU admission for SARS-CoV-2 did not efficiently predict the 28-day mortality rate. Performance was better for non-intubated patients at admission. Performance of biological cardiac markers may be equivalent to the LUS score.
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http://dx.doi.org/10.1007/s12325-021-01702-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045017PMC
May 2021

Micafungin population PK analysis in plasma and peritoneal fluid in septic patients with intra-abdominal infections: a prospective cohort study.

Antimicrob Agents Chemother 2021 Apr 12. Epub 2021 Apr 12.

Service des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France.

To describe the pharmacokinetics (PK) of micafungin in plasma and peritoneal fluid in septic patients with intra-abdominal infections. Twelve patients with secondary peritonitis in septic shock receiving 100 mg micafungin once daily were included. Total micafungin plasma and peritoneal fluid were subject to a population pharmacokinetic analysis using Pmetrics®. Monte Carlo simulations were performed considering total AUC/MIC ratios in plasma. Micafungin concentrations in both plasma and peritoneal exudate were best described by a three-compartmental PK model with the fat free mass (FFM) as a covariate of clearance (CL) and volume of the central compartment (Vc). The mean parameter estimates (standard deviation, SD) were 1.18 (0.40) L/h for CL and 12.85 (4.78) L for Vc. The mean peritoneal exudate/plasma ratio (SD) of micafungin was 25% (5%) on day 1 and 40% (8%) between day 3-5. Dosing simulations supported the use of standard 100 mg daily dosing for (FFM < 60 kg), (FFM < 50 kg) and (FFM < 30 kg) on the second day of therapy. There is a moderate penetration of micafungin into peritoneal cavity (25 to 40%). For empirical treatment, a dose escalation of at least a loading dose of 150 mg depending on the FFM of patients and Candida species is suggested to be effective from the first day of therapy.
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http://dx.doi.org/10.1128/AAC.02307-20DOI Listing
April 2021

Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Biomedicine, University of Basel, 4051 Basel, Switzerland.

Glioblastomas are among the most aggressive tumors, and with low survival rates. They are characterized by the ability to create a highly immunosuppressive tumor microenvironment. Exosomes, small extracellular vesicles (EVs), mediate intercellular communication in the tumor microenvironment by transporting various biomolecules (RNA, DNA, proteins, and lipids), therefore playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Exosomes are found in all body fluids and can cross the blood-brain barrier due to their nanoscale size. Recent studies have highlighted the multiple influences of tumor-derived exosomes on immune cells. Owing to their structural and functional properties, exosomes can be an important instrument for gaining a better molecular understanding of tumors. Furthermore, they qualify not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting aggressive tumor cells, like glioblastomas.
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http://dx.doi.org/10.3390/ijms22073600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036988PMC
March 2021

An international survey on aminoglycoside practices in critically ill patients: the AMINO III study.

Ann Intensive Care 2021 Mar 19;11(1):49. Epub 2021 Mar 19.

Department of Intensive Care Medicine, Division of Anesthesiology, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, Place du Professeur Robert Debré, 30 029, Nîmes cedex 9, France.

Background: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock.

Results: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of C and C was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a C/MIC > 8 and 353 (71%) having concentrations above C recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes.

Conclusion: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.
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http://dx.doi.org/10.1186/s13613-021-00834-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979853PMC
March 2021

A Loading Micafungin Dose in Critically Ill Patients Undergoing Continuous Veno-Venous Hemofiltration or Continuous Veno-Venous Hemodiafiltration: A Population Pharmacokinetic Analysis.

Ther Drug Monit 2021 Feb 8. Epub 2021 Feb 8.

Service des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, Centre Hospitalier Universitaire (CHU) Nîmes, Nîmes, France Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Univ Montpellier, Montpellier, France Equipe d'accueil 2992 Caractéristiques Féminines des Interfaces Vasculaires (IMAGINE), Faculté de médecine, Univ Montpellier, Montpellier, France Laboratoire de Biochimie, CHU Nîmes, Hôpital Carémeau, Nîmes, France Department of Anesthesia and Surgical Intensive Care, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain Universidad Autónoma de Madrid, Madrid, Spain Pharmacy Department. Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. Infectious Pathology and Antimicrobials Research Group (IPAR). Institut Hospital del Mar d'Investigacions Mèdiques (IMIM). Pharmacy Department. Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. Universitat Auto[Combining Grave Accent]noma de Barcelona, Barcelona, Spain. UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Background: In the present study, the authors aimed to compare the pharmacokinetics (PK) of micafungin in critically ill patients receiving continuous veno-venous hemofiltration (CVVH, 30 mL/kg/h) with those of patients receiving equidoses of hemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h) and determine the optimal dosing regimen using the developed model.

Methods: Patients with septic shock undergoing continuous renal replacement therapy (CRRT) and receiving a conventional dose of 100 mg micafungin once daily were eligible for inclusion. Total micafungin plasma concentrations from eight CVVH sessions and eight CVVHDF sessions were subjected to a population PK analysis using Pmetrics. Validation of the model performance was reinforced by external validation. Monte Carlo simulations were performed considering the total ratio of free drug area under the curve (AUC) over 24 h to the minimum inhibitory concentration (MIC) (AUC0-24/MIC) in plasma.

Results: The median total body weight (min-max) was 94.8 (66-138) kg. Micafungin concentrations were best described by a two-compartmental PK model. No covariates, including CRRT modality (CVVH or CVVHDF), were retained in the final model. The mean parameter estimates (standard deviation) were 0.96 (0.32) L/h for clearance and 14.8 (5.3) L for the central compartment volume. External validation confirmed the performance of the developed PK model. Dosing simulations did not support the use of standard 100 mg daily dosing, except for Candida albicans on the second day of therapy. A loading dose of 150 mg followed by 100 mg daily reached the probability of target attainment for all C. albicans and C. glabrata, but not for C. krusei and C. parapsilosis.

Conclusions: No difference was observed in micafungin PK between equidoses of CVVH and CVVHDF. A loading dose of 150 mg is required to achieve the PK/PD target for less susceptible Candida species from the first day of therapy.
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http://dx.doi.org/10.1097/FTD.0000000000000874DOI Listing
February 2021

Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs.

Biomaterials 2021 01 19;268:120594. Epub 2020 Dec 19.

Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS UMR7241, INSERM U1050, PSL Research University, Paris, France. Electronic address:

Blood perfusion of grafted tissue constructs is a hindrance to the success of stem cell-based therapies by limiting cell survival and tissue regeneration. Implantation of a pre-vascularized network engineered in vitro has thus emerged as a promising strategy for promoting blood supply deep into the construct, relying on inosculation with the host vasculature. We aimed to fabricate in vitro tissue constructs with mature microvascular networks, displaying perivascular recruitment and basement membrane, taking advantage of the angiogenic properties of dental pulp stem cells and self-assembly of endothelial cells into capillaries. Using digital scanned light-sheet microscopy, we characterized the generation of dense microvascular networks in collagen hydrogels and established parameters for quantification of perivascular recruitment. We also performed original time-lapse analysis of stem cell recruitment. These experiments demonstrated that perivascular recruitment of dental pulp stem cells is driven by PDGF-BB. Recruited stem cells participated in deposition of vascular basement membrane and vessel maturation. Mature microvascular networks thus generated were then compared to those lacking perivascular coverage generated using stem cell conditioned medium. Implantation in athymic nude mice demonstrated that in vitro maturation of microvascular networks improved blood perfusion and cell survival within the construct. Taken together, these data demonstrate the strong potential of in vitro production of mature microvasculature for improving cell-based therapies.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120594DOI Listing
January 2021

The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins.

Cancers (Basel) 2020 Dec 29;13(1). Epub 2020 Dec 29.

Univ Lyon, University Claude Bernard Lyon 1, CNRS, INSA Lyon, CPE, Institute of Molecular and Supramolecular Chemistry and Biochemistry, UMR 5246, F-69622 Villeurbanne CEDEX, France.

The members of the lysyl oxidase (LOX) family are amine oxidases, which initiate the covalent cross-linking of the extracellular matrix (ECM), regulate ECM stiffness, and contribute to cancer progression. The aim of this study was to build the first draft of the interactome of the five members of the LOX family in order to determine its molecular functions, the biological and signaling pathways mediating these functions, the biological processes it is involved in, and if and how it is rewired in cancer. In vitro binding assays, based on surface plasmon resonance and bio-layer interferometry, combined with queries of interaction databases and interaction datasets, were used to retrieve interaction data. The interactome was then analyzed using computational tools. We identified 31 new interactions and 14 new partners of LOXL2, including the α5β1 integrin, and built an interactome comprising 320 proteins, 5 glycosaminoglycans, and 399 interactions. This network participates in ECM organization, degradation and cross-linking, cell-ECM interactions mediated by non-integrin and integrin receptors, protein folding and chaperone activity, organ and blood vessel development, cellular response to stress, and signal transduction. We showed that this network is rewired in colorectal carcinoma, leading to a switch from ECM organization to protein folding and chaperone activity.
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http://dx.doi.org/10.3390/cancers13010071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794802PMC
December 2020

TP53 and PTEN as driver mutations in Zenker's carcinoma-a clinical presentation.

Clin Case Rep 2020 Dec 1;8(12):2791-2797. Epub 2020 Sep 1.

Department of Otorhinolaryngology and Biomedicine University Hospitals Basel Basel Switzerland.

Zenker carcinoma is still being treated empirically because of the lack of evidence- based guidelines. We report for the first time about the genetic examination of this rare entity. The revealed mutations show genetic similarities with HPV(-)HNSCC which suggests that well-known therapeutic strategies may be applicable for this disease.
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http://dx.doi.org/10.1002/ccr3.3169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752333PMC
December 2020

3D Systems to Model Tumor Angiogenesis and Interactions With Stromal Cells.

Front Cell Dev Biol 2020 5;8:594903. Epub 2020 Nov 5.

Center for Interdisciplinary Research in Biology, College de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.

3D culture systems provide promising tools for screening novel therapies and understanding drug resistance mechanisms in cancer because they are adapted for high throughput analysis. One of the main current challenges is to reproducibly culture patient samples containing cancer and stromal cells to faithfully recapitulate tumor microenvironment and move toward efficient personalized medicine. Tumors are composed of heterogeneous cell populations and characterized by chaotic vascularization in a remodeled microenvironment. Indeed, tumor angiogenesis occurs in a complex stroma containing immune cells and cancer-associated fibroblasts that secrete important amounts of cytokines, growth factors, extracellular vesicles, and extracellular matrix (ECM). This process leads to the formation of inflated, tortuous, and permeable capillaries that display deficient basement membrane (BM) and perivascular coverage. These abnormal capillaries affect responses to anti-cancer therapies such as anti-angiogenic, radio-, and immunotherapies. Current pre-clinical models are limited for investigating interactions between tumor cells and vascularization during tumor progression as well as mechanisms that lead to drug resistance. approaches developed for vascularization are either the result of engineered cell lining or based on physiological processes including vasculogenesis and sprouting angiogenesis. They allow investigation of paracrine and direct interactions between endothelial and tumor and/or stromal cells, as well as impact of biochemical and biophysical cues of the microenvironment, using either natural matrix components or functionalized synthetic hydrogels. In addition, microfluidic devices provide access to modeling the impact of shear stress and interstitial flow and growth factor gradients. In this review, we will describe the state of the art co-culture models of vascularized micro-tumors in order to study tumor progression and metastatic dissemination including intravasation and/or extravasation processes.
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http://dx.doi.org/10.3389/fcell.2020.594903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674638PMC
November 2020

Prognostic value and time course evolution left ventricular global longitudinal strain in septic shock: an exploratory prospective study.

J Clin Monit Comput 2020 Nov 20. Epub 2020 Nov 20.

Department of Anaesthesiology, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, Place du Professeur Robert Debré, 30 029 cedex 9, Nîmes, France.

Our main objective was to describe the course of GLS during the first days of septic shock and to assess the agreement between GLS values and longitudinal strain measured in apical four chambers. A prospective observational single centre study was conducted at the Nimes University Hospital's ICU. All patients admitted for a diagnosis of septic shock without pre-existing heart disease were eligible. Echocardiography (LVEF and GLS) was performed on the first day, and repeated once between day 3 and day 5 then once between day 6 and day 8. We enrolled 40 consecutive patients. Four patients were excluded. In overall population, GLS at T1 was impaired (- 11.0%, IQR(interquartile range) [- 15; - 10]). On T2 exams, a significant improvement of the GLS (- 11% vs - 16% p = 0.02) was observed whereas LVEF remained stable over time. A good agreement between GLS and longitudinal strain measured on a four chambers view was found. Based on the Bland and Altman method, the mean of differences for T1 exams was 0.1 (95% CI [- 0.6; 0.8]) with limits of agreement ranging from - 4 to 4. Myocardial strain is depressed at the early phase of septic shock and improves over time. A single measurement of LS4C view appears sufficient at bedside.
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http://dx.doi.org/10.1007/s10877-020-00620-wDOI Listing
November 2020

Magnetic needle-tracking device for ultrasound guidance of radial artery puncture: A randomized study on a simulation model.

J Clin Ultrasound 2021 Mar 16;49(3):212-217. Epub 2020 Nov 16.

Montpellier University, Department of Anesthesiology, Emergency and Critical Care Medicine, Intensive Care Unit, Nîmes University Hospital, Nîmes, France.

Introduction: Ultrasound-guidance of radial artery catheter insertion improves the first attempt success and reduces the occurrence of hematomas. Needle-tracking devices optimize needle-ultrasound beam alignment by displaying in real-time the needle tip position. We compared the median time need by experienced physicians to achieve radial artery puncture using either a conventional ultrasonography device (CUD) or a magnetic needle-tracking ultrasound device (MUD) in a simulation training arm model.

Methods: Fifty experienced residents and physicians performed two punctures in randomized order with the CUD and the MUD. The primary outcome was puncture duration; the secondary outcomes were puncture success, rate of accidental vein puncture, and practitioner's comfort (subjective scale 0-10).

Results: The median [lower-upper quartile] puncture time was 10 [6-14] seconds when using CUD and 4 [3-7] seconds when using MUD (P < .01). In the multivariate analysis, MUD use was associated with decreased puncture duration whatever the puncture order (OR 1.13 [1.07-1.20], P < .01). The participants performed 99 (99%) successful punctures: 50 with the MUD (100%) and 49 with the CUD (98%). There was no accidental venous puncture. The practitioner's comfort level was 6.5 [6, 7] with the CUD and 8 [7-9] with the MUD (P < .01).

Conclusion: MUD reduced radial artery puncture time and improved physician comfort in a simulation training arm model.
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http://dx.doi.org/10.1002/jcu.22945DOI Listing
March 2021

Vancomycin Serum Concentration after 48 h of Administration: A 3-Years Survey in an Intensive Care Unit.

Antibiotics (Basel) 2020 Nov 10;9(11). Epub 2020 Nov 10.

Service des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, 30029 Nîmes, France.

The present study assessed the proportion of intensive care unit (ICU) patients who had a vancomycin serum concentration between 20 and 25 mg/L after 24-48 h of intravenous vancomycin administration. From 2016 to 2018, adult ICU patients with vancomycin continuous infusion (CI) for any indication were included. The primary outcome was the proportion of patients with a first-available vancomycin serum concentration between 20-25 mg/L at 24 h (D2) or 48 h (D3). Of 3894 admitted ICU patients, 179 were included. A median loading dose of 15.6 (interquartile range (IQR) = (12.5-20.8) mg/kg) was given in 151/179 patients (84%). The median daily doses of vancomycin infusion for D1 and D2 were 2000 [(IQR (1600-2000)) and 2000 (IQR (2000-2500)) mg/d], respectively. The median duration of treatment was 4 (2-7) days. At D2 or D3, the median value of first serum vancomycin concentration was 19.8 (IQR (16.0-25.1)) with serum vancomycin concentration between 20-25 mg/L reported in 43 patients (24%). Time spent in the ICU before vancomycin initiation was the only risk factor of non-therapeutic concentration at D2 or D3. Acute kidney injury occurred significantly more when vancomycin concentration was supra therapeutic at D2 or D3. At D28, 44 (26%) patients had died. These results emphasize the need of appropriate loading dose and regular monitoring to improve vancomycin efficacy and avoid renal toxicity.
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http://dx.doi.org/10.3390/antibiotics9110793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698174PMC
November 2020

Diaphragmatic excursion measurement in emergency department patients with acute dyspnea to predict mechanical ventilation use.

Am J Emerg Med 2020 10 26;38(10):2081-2087. Epub 2020 Jun 26.

Montpellier University, Department of Anesthesiology, Emergency and Critical Care Medicine, Intensive Care Unit, Nîmes University Hospital, place du Pr Debré, 30029 Nîmes, France. Electronic address:

Introduction: Ultrasound is a feasible and reproducible method for measuring right diaphragmatic excursion (RDE) in ED patients with acute dyspnea (AD). In AD patients, the correlation between the RDE value and the need for mechanical ventilation (MV) is not known.

Materials: This was a bicentric, observational prospective study. The RDE measurement was done at admission. The need for MV was defined by the use of MV within 4 h of AD management. An optimal threshold for RDE was determined as the value that minimized the incorrect predictions of the use of MV in the first 4 h as the highest Youden index.

Results: We analyzed 102 patients (79 [70; 86] years), 38 (37%) of whom had been ventilated. The RDE value was 1.7 cm [1.4; 2.0] and 2.2 cm [1.8; 2.6] in the ventilated and non-ventilated groups, respectively (p = 0.06). The AUC was 0.68 95% CI [0.57; 0.80]. With a threshold of 2 cm, the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 76% [60%; 89%], 59% [46%; 71%], 81% [67%; 91%], and 53% [39%; 66%], respectively. In the non-COPD patients, the RDE values were 1.5 cm [1.2; 1.9] and 2.2 cm [1.8; 2.6] (p < 0.01) in the ventilated and not-ventilated groups, respectively. The AUC was 0.77 95% CI [0.64; 0.90]. With a threshold of 2.18 cm, the sensitivity, specificity, NPV, and PPV were 91% [71%; 99%], 51% [36%; 66%], 92% [75%; 99%], and 54% [38%; 69%], respectively.

Conclusion: The RDE values at ED admission were unable to define a prognostic threshold value associated with subsequent MV need in the AD patients. In non-COPD patients, the NPV was 92%.
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http://dx.doi.org/10.1016/j.ajem.2020.06.044DOI Listing
October 2020

Extracellular vesicles in cancer progression: are they part of the problem or part of the solution?

Nanomedicine (Lond) 2020 11 23;15(26):2625-2641. Epub 2020 Oct 23.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, 90035-003, Brazil.

Extracellular vesicles (EVs) are released especially by cancer cells. They modulate the tumor microenvironment by interacting with immune cells while carrying immunosuppressive or immunostimulatory molecules. In this review, we will explore some conflicting reports regarding the immunological outcomes of EVs in cancer progression, in which they might initiate an antitumor immune response or an immunosuppressive response. Concerning immunosuppression, the role of tumor-derived EVs' in the adenosinergic system is underexplored. The enhancement of adenosine (ADO) levels in the tumor microenvironment impairs T-cell function and cytokine release. However, some tumor-derived EVs may deliver immunostimulatory factors, promoting immunogenic activity, even with ADO production. The modulatory role of ADO over the tumor progression represents a piece in an intricate microenvironment with anti and pro tumoral seesaw-like mechanisms.
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http://dx.doi.org/10.2217/nnm-2020-0256DOI Listing
November 2020

Choice of fluid for critically ill patients: An overview of specific situations.

Anaesth Crit Care Pain Med 2020 12 19;39(6):837-845. Epub 2020 Oct 19.

Aix Marseille Université, Assistance Publique Hôpitaux de Marseille, Service d'Anesthésie et de Réanimation, Hôpital Nord, 13005 Marseille, France.

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http://dx.doi.org/10.1016/j.accpm.2020.10.003DOI Listing
December 2020

A national healthcare response to intensive care bed requirements during the COVID-19 outbreak in France.

Anaesth Crit Care Pain Med 2020 Dec 5;39(6):709-715. Epub 2020 Oct 5.

Department of Anaesthesiology and Critical Care Medicine, Lapeyronie University Hospital and Montpellier University. INSERM unit 1051, Montpellier Neurosciences Institute, Montpellier, France.

Background: Whereas 5415 Intensive Care Unit (ICU) beds were initially available, 7148 COVID-19 patients were hospitalised in the ICU at the peak of the outbreak. The present study reports how the French Health Care system created temporary ICU beds to avoid being overwhelmed.

Methods: All French ICUs were contacted for answering a questionnaire focusing on the available beds and health care providers before and during the outbreak.

Results: Among 336 institutions with ICUs before the outbreak, 315 (94%) participated, covering 5054/5531 (91%) ICU beds. During the outbreak, 4806 new ICU beds (+95% increase) were created from Acute Care Unit (ACU, 2283), Post Anaesthetic Care Unit and Operating Theatre (PACU & OT, 1522), other units (374) or real build-up of new ICU beds (627), respectively. At the peak of the outbreak, 9860, 1982 and 3089 ICU, ACU and PACU beds were made available. Before the outbreak, 3548 physicians (2224 critical care anaesthesiologists, 898 intensivists and 275 from other specialties, 151 paediatrics), 1785 residents, 11,023 nurses and 6763 nursing auxiliaries worked in established ICUs. During the outbreak, 2524 physicians, 715 residents, 7722 nurses and 3043 nursing auxiliaries supplemented the usual staff in all ICUs. A total number of 3212 new ventilators were added to the 5997 initially available in ICU.

Conclusion: During the COVID-19 outbreak, the French Health Care system created 4806 ICU beds (+95% increase from baseline), essentially by transforming beds from ACUs and PACUs. Collaboration between intensivists, critical care anaesthesiologists, emergency physicians as well as the mobilisation of nursing staff were primordial in this context.
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http://dx.doi.org/10.1016/j.accpm.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534597PMC
December 2020

What Makes a Front-of-Pack Nutritional Labelling System Effective: The Impact of Key Design Components on Food Purchases.

Nutrients 2020 Sep 19;12(9). Epub 2020 Sep 19.

University Grenoble Alpes, INRAE, CNRS, Grenoble INP, GAEL, 38000 Grenoble, France.

The relative impacts on food purchases of many alternative front-of-pack nutritional labelling systems were tested, with various methods-from opinion pool to nationwide experiments. Clearly, some systems induce better purchasing responses, having better nutritional impacts on food baskets. Nonetheless, we still ignore what the ingredients of an efficient label are. Here, we propose guidance for label designers. To do so, we first propose a typology that breaks down established labelling systems into four elementary components: , , and . On this basis, we then build seven alternative generic labelling systems that we test in a framed-field experiment enabling us to measure the effect of each component on food purchases in isolation. Our results show that an effective front-of-pack labelling system should be Food-Directive (instead of Diet-Directive) and be displayed on both healthy and unhealthy food. The reference set, which is across categories or within categories, produces the same average nutrition score but generates contrasting behavioural responses.
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http://dx.doi.org/10.3390/nu12092870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551239PMC
September 2020

Haemodynamic monitoring of COVID-19 patients: Classical methods and new paradigms.

Anaesth Crit Care Pain Med 2020 10 4;39(5):551-552. Epub 2020 Sep 4.

Department of Anaesthesia, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, France; University of Montpellier, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473332PMC
October 2020

Global longitudinal strain changes during hemorrhagic shock: An experimental study.

Turk J Emerg Med 2020 Jul-Sep;20(3):97-104. Epub 2020 Jul 18.

Department of Anesthesiology, Critical Care, Montpellier University, Pain and Emergency Medicine, Nîmes University Hospital, Nîmes, France.

Objectives: Global longitudinal strain (GLS) appears sensitive and reproducible to identify left ventricular systolic dysfunction. The main objective was to analyze the GLS changes in an anesthetized-piglet model of controlled hemorrhagic shock (HS). The secondary objective was to evaluate if GLS changes was different depending on the expansion fluid treatment with or without norepinephrine.

Methods: Eighteen anesthetized and ventilated piglets were bled until the mean arterial pressure reached 40 mmHg. Controlled hemorrhage was maintained for 30 min before randomizing the piglets to three resuscitation groups: control group, LR group (resuscitated with lactated ringer), and NA group (resuscitated with lactated ringer and norepinephrine).

Results: There was no difference in the baseline hemodynamic, biological, and ultrasound data among the three groups. During the hemorrhagic phase, the GLS increased significantly from 25 mL/kg of depletion. During the resuscitation phase, the GLS decreased significantly from 20 mL/kg of fluid administration. There was no difference in GLS variation among the groups during the hemorrhagic, maintenance, and resuscitation phases.

Conclusion: In our HS model, GLS increased with hemorrhage and decreased during resuscitation, showing its preload dependence.
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http://dx.doi.org/10.4103/2452-2473.290066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416855PMC
July 2020

Continuous lactate monitoring in critically ill patients using microdialysis.

Anaesth Crit Care Pain Med 2020 08 10;39(4):513-517. Epub 2020 Jul 10.

Service des réanimations, centre hospitalier universitaire de Nîmes, place du Pr. Robert-Debré, 30029 Nîmes, France.

Introduction: Blood lactate is a strong predictor of mortality in critically ill patients. Its monitoring implies repeated measurements. The EIRUS™ system (Maquet Critical Care AB, 17154, Solna, Sweden) is a new device allowing continuous lactate monitoring by intravascular micro dialysis. The present study aimed at assessing the accuracy of the EIRUS™ system in critically ill patients with circulatory failure.

Methods: An observational cohort study was conducted in Nîmes University Hospital. Eligible patients were those with circulatory failure in which a specific central venous access was put in place by the physician in charge, allowing continuous lactate measurement by the EIRUS™ system. Lactate measurements obtained by the system were compared to lactate from arterial blood samples at H4 and H8 from the calibration, during the first 48hours of shock.

Results: In all, 28 patients were included providing 244 pairs of measures. The Bland-Altman analysis showed a bootstrapped mean bias at H4 of 0.05 and 95% limits of agreement of -0.9 to 1.0mmol/L. At H8 the mean bias was 0.06 and 95% limits of agreement -1.1 to 1.2mmol/L. The global trend agreement [95% CI] for a pre-specified arbitrary threshold of 1mmol/L, defining clinically significant variations, between H0 and H4 and H4 and H8 was 91.6% [85.1; 95.9] and 89.5% [82.3; 94.4], respectively.

Conclusion: The EIRUS™ device provided an overall accurate measurement of lactate in critically ill patients with circulatory failure. Detection of lactate variations over time is less precise and technical issues may limit its clinical use.
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http://dx.doi.org/10.1016/j.accpm.2020.05.018DOI Listing
August 2020

Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC).

Int J Mol Sci 2020 Jun 18;21(12). Epub 2020 Jun 18.

Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.

Exosomes are nanovesicles part of a recently described intercellular communication system. Their properties seem promising as a biomarker in cancer research, where more sensitive monitoring and therapeutic applications are desperately needed. In the case of head and neck squamous cell carcinoma (HNSCC), overall survival often remains poor, although huge technological advancements in the treatment of this disease have been made. In the following review, diagnostic and therapeutic properties are highlighted and summarised. Impressive first results have been obtained but more research is needed to implement these innovative techniques into daily clinical routines.
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http://dx.doi.org/10.3390/ijms21124344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352611PMC
June 2020

Guidelines: Anaesthesia in the context of COVID-19 pandemic.

Anaesth Crit Care Pain Med 2020 06 5;39(3):395-415. Epub 2020 Jun 5.

Department of Anaesthesiology and Intensive Care, DMU DREAM, AP-HP, 6 Sorbonne Université, Paris, France; Clinique Remusat, 75016 Paris, France; Clinique Jouvenet, 75016 Paris, France.

Objectives: The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic.

Methods: The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions.

Results: The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms.

Conclusion: We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.
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http://dx.doi.org/10.1016/j.accpm.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274119PMC
June 2020

Prioritisation of ICU treatments for critically ill patients in a COVID-19 pandemic with scarce resources.

Anaesth Crit Care Pain Med 2020 06 17;39(3):333-339. Epub 2020 May 17.

Charles Nicolle hospital & Rouen Normandie University, Rouen, France; Ethics committee, French society of anaesthesia and critical care (SFAR), Paris, France.

Background: Relying on capacity increases and patient transfers to deal with the huge and continuous inflow of COVID-19 critically ill patients is a strategy limited by finite human and logistical resources.

Rationale: Prioritising both critical care initiation and continuation is paramount to save the greatest number of lives. It enables to allocate scarce resources in priority to those with the highest probability of benefiting from them. It is fully ethical provided it relies on objective and widely shared criteria, thus preventing arbitrary decisions and guaranteeing equity. Prioritisation seeks to fairly allocate treatments, maximise saved lives, gain indirect life benefits from prioritising exposed healthcare and similar workers, give priority to those most penalised as a last resort, and apply similar prioritisation schemes to all patients.

Prioritisation Strategy: Prioritisation schemes and their criteria are adjusted to the level of resource scarcity: strain (level A) or saturation (level B). Prioritisation yields a four level priority for initiation or continuation of critical care: P1-high priority, P2-intermediate priority, P3-not needed, P4-not appropriate. Prioritisation schemes take into account the patient's wishes, clinical frailty, pre-existing chronic condition, along with severity and evolution of acute condition. Initial priority level must be reassessed, at least after 48h once missing decision elements are available, at the typical turning point in the disease's natural history (ICU days 7 to 10 for COVID-19), and each time resource scarcity levels change. For treatments to be withheld or withdrawn, a collegial decision-making process and information of patient and/or next of kin are paramount.

Perspective: Prioritisation strategy is bound to evolve with new knowledge and with changes within the epidemiological situation.
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http://dx.doi.org/10.1016/j.accpm.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230138PMC
June 2020

Should we ban hydroxyethyl starches from the operating theatre? CON, PRO or something else?

Authors:
Laurent Muller

Anaesth Crit Care Pain Med 2020 Apr 7;39(2):189-190. Epub 2020 Mar 7.

Service Réanimation et Surveillance Continue, Pôle ARDU (anesthésie, réanimation, douleur, urgences), CHU de Nîmes-Careameau, 30029 Nîmes cedex, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2020.03.008DOI Listing
April 2020

Physical activity rather than sedentary behaviour is socially determined in French adolescents with overweight and obesity.

Prev Med 2020 05 22;134:106043. Epub 2020 Feb 22.

National Conservatory of Arts and Crafts (CNAM), F-54000 Nancy, France.

Social differences in prevalence of overweight and obesity among adolescents, known as the weight social gradient, could be explained by differences in behaviours between social classes. This study examined the respective association of physical activity (PA), sedentary behaviour (SB) and weight status with adolescents' socioeconomic status. We used cross-sectional data for 1935 adolescents (13-18 years old) with overweight or obesity who participated in the PRALIMAP-INÉS (PRomotion de l'ALImentation et de l'Activité Physique - INÉgalités de Santé) trial conducted in northeastern France between 2012 and 2015. Adolescents completed the International Physical Activity Questionnaire for PA and SB and the Family Affluence Scale for socioeconomic status. Weight status was assessed by the body mass index (BMI) and BMI z-score. Social gradient of weight status, PA and SB were described according to the Family Affluence Scale (slopes) and evidenced by the linear trend test (p). Adolescents' socioeconomic status was positively associated with PA practice (frequency, vigorous PA and leisure-time PA), but there was no association with their SB. The results confirmed a significant weight social gradient: BMI (β = 0.37, p < .0001) and BMI z-score (β = 0.07, p = .0001). The weight social gradient in adolescents was mostly associated with PA (5.7% to 8.1%) rather than SB (2.7% to 5.7%). Nearly 14% of BMI z-scores could be related to a combined PA and SB effect. PA was found an important factor of weight social gradient in adolescence. Actions aimed at preventing weight social inequalities among adolescents could include PA promotion as lever. CLINICAL TRIALS REGISTRY AND NUMBER: ClinicalTrials.gov (NCT01688453).
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http://dx.doi.org/10.1016/j.ypmed.2020.106043DOI Listing
May 2020

Effectiveness of a socially adapted intervention in reducing social inequalities in adolescence weight. The PRALIMAP-INÈS school-based mixed trial.

Int J Obes (Lond) 2020 04 22;44(4):895-907. Epub 2020 Jan 22.

University of Lorraine, EA 4360 APEMAC, Nancy Metz, France.

Background: A high prevalence of overweight/obesity among low socioeconomic status adolescents contributes to health inequalities. However, evidence-based interventions for reducing social inequalities in adolescent weight are lacking. We aimed to investigate whether strengthened care management for adolescents with low socioeconomic status has an equivalent effect in reducing overweight as standard care management in adolescents with high status.

Methods: PRALIMAP-INÈS was a multicentre trial including 35 state-run high and middle schools in the north-eastern France. A population-based sample of 1639 adolescents aged 13-18 years with screened and clinically confirmed overweight/obesity were proposed for inclusion and divided into two groups by the Family Affluence Scale score: advantaged (score > 5), receiving standard care management (A.S) and less-advantaged randomly assigned to two groups (1:2 ratio): standard care management (LA.S) and standard and strengthened care management (LA.S.S). Interventions were based on the proportionate universalism principle: universal standard care for all groups and proportionate care for the LA.S.S group. Main outcome was body mass index z-score (BMIz) assessed before and 1 year after inclusion.

Results: A total of 1419 adolescents were included and 1143 followed up at 1 year: 649 in A.S, 158 in LA.S and 336 in LA.S.S groups. BMIz decreased significantly for boys (-0.11 [95% CI, -0.13 to -0.08]; p < 0.0001) and girls (-0.05 [-0.08 to -0.03]; p < 0.0001). No equivalence between LA.S.S and A.S groups was evidenced. For girls, the trend to superiority for LA.S.S was confirmed by the more favourable change (-0.06 [-0.11 to -0.01]; p = 0.01) observed on superiority analysis, with no differential change for boys (0.02 [-0.03 to 0.08]; p = 0.41).

Conclusions: A public health school-based intervention using the proportionate universalism principle may be effective in not worsening or even reducing overweight social inequalities in adolescents, especially for girls. Overcoming social barriers may help health professionals dealing with the burden and inequalities of overweight in adolescents.
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http://dx.doi.org/10.1038/s41366-020-0520-zDOI Listing
April 2020

Focused Cardiac Ultrasound: A Prospective Randomized Study of Simulator-Based Training.

J Am Soc Echocardiogr 2020 03 19;33(3):404-406. Epub 2019 Dec 19.

Department of Anesthesiology, Emergency and Critical Care Medicine, Intensive Care Unit, Nîmes University Hospital, Montpellier University, Nîmes, France; Medical Faculty of Nîmes, University Hospital Unit of Simulation of Nîmes, Nîmes, France; Emergency Department, Timone 2 Hospital, Aix-Marseille University, Marseille, France.

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http://dx.doi.org/10.1016/j.echo.2019.10.010DOI Listing
March 2020