Publications by authors named "Gilles Capellier"

92 Publications

Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study.

Ann Intensive Care 2021 Oct 12;11(1):145. Epub 2021 Oct 12.

Medical Intensive Care Unit, University Hospital, Besançon, France.

Background: In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients.

Methods: The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician's discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU.

Results: From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant.

Conclusion: The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.
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http://dx.doi.org/10.1186/s13613-021-00931-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505789PMC
October 2021

An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism: The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score.

Chest 2021 Jul 2. Epub 2021 Jul 2.

Department of Cardiology, University Hospital Jean Minjoz, Besançon, France; EA3920, University of Burgundy Franche-Comté, Besançon, France; F-CRIN, INNOVTE network, France.

Background: Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management.

Research Question: Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding?

Study Design And Methods: From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED, RIETE, and BACS models.

Results: Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin <12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate <60 mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI; 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not.

Interpretation: The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.
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http://dx.doi.org/10.1016/j.chest.2021.06.048DOI Listing
July 2021

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

Ann Intensive Care 2021 Jun 4;11(1):90. Epub 2021 Jun 4.

Service de Médecine Intensive Réanimation-Unité de Sevrage Ventilatoire et Réhabilitation, CH de Bethune, Bethune, France.

Background: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France.

Methods: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses.

Results: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11.

Conclusion: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).
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http://dx.doi.org/10.1186/s13613-021-00880-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177250PMC
June 2021

Extracorporeal Membrane Oxygenation Cannula-Related Infections: Epidemiology and Risk Factors.

ASAIO J 2021 Jun 1. Epub 2021 Jun 1.

From the Medical Intensive Care Unit, University Hospital, Besancon, France Research Unit EA 3920, University of Franche Comte, Besancon, France Anaesthesia and Surgical Intensive Care Unit, University Hospital, Besancon, France Bacteriology Department, University Hospital, Besancon, France Cardiac Surgery Unit, University Hospital, Besancon, France Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Clayton, Australia.

Although being a potential major source of infection in extracorporeal membrane oxygenation (ECMO) patients, data regarding cannula-related infections (CRI) remain scarce. We therefore aimed at describing the epidemiology of CRI among critically ill patients supported by ECMO. Between October 2017 and November 2019, adult patients supported by either venoarterial (VA), venopulmonary arterial, or venovenous (VV) ECMO for more than 24 hours were prospectively enrolled. When CRI was suspected, cannula swab and subcutaneous needle aspirate samples were obtained for microbiological culture. Cannula tips were systematically sent for culture at the time of ECMO removal. Primary end-point was CRI, which was defined by sepsis or local sign of cannula infection and at least one positive culture among swab, subcutaneous needle aspirate or tip. Multivariate analysis was performed to identify risk factors of CRI. Hundred patients were included, including 77 VA, 12 venopulmonary arterial, and 11 VV ECMO. Cannula-related infections were diagnosed after a median duration of ECMO of 10 [7-13] days. Rate of CRI was 24%, including 10% with bacteremia. Most frequent involved pathogens were Enterobacteriaceae (n = 14), Enterococci (n = 8), and coagulase-negative Staphylococci (n = 7). By multivariate analysis, diabetes and ECMO duration were independently associated with CRI.
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http://dx.doi.org/10.1097/MAT.0000000000001505DOI Listing
June 2021

An international tool to measure perceived stressors in intensive care units: the PS-ICU scale.

Ann Intensive Care 2021 Apr 10;11(1):57. Epub 2021 Apr 10.

Medical Intensive Care Unit, University Hospital of Besançon, University of Franche-Comte EA 3920, Besançon, France.

Background: The intensive care unit is increasingly recognized as a stressful environment for healthcare professionals. This context has an impact on the health of these professionals but also on the quality of their personal and professional life. However, there is currently no validated scale to measure specific stressors perceived by healthcare professionals in intensive care. The aim of this study was to construct and validate in three languages a perceived stressors scale more specific to intensive care units (ICU).

Results: We conducted a three-phase study between 2016 and 2019: (1) identification of stressors based on the verbatim of 165 nurses and physicians from 4 countries (Canada, France, Italy, and Spain). We identified 99 stressors, including those common to most healthcare professions (called generic), as well as stressors more specific to ICU professionals (called specific); (2) item elaboration and selection by a panel of interdisciplinary experts to build a provisional 99-item version of the scale. This version was pre-tested with 70 professionals in the 4 countries and enabled us to select 50 relevant items; (3) test of the validity of the scale in 497 ICU healthcare professionals. Factor analyses identified six dimensions: lack of fit with families and organizational functioning; patient- and family-related emotional load; complex/at risk situations and skill-related issues; workload and human resource management issues; difficulties related to team working; and suboptimal care situations. Correlations of the PS-ICU scale with a generic stressors measure (i.e., the Job Content Questionnaire) tested its convergent validity, while its correlations with the Maslach Burnout Inventory-HSS examined its concurrent validity. We also assessed the test-retest reliability of PS-ICU with intraclass correlation coefficients.

Conclusions: The perceived stressors in intensive care units (PS-ICU) scale have good psychometric properties in all countries. It includes six broad dimensions covering generic or specific stressors to ICU, and thus, enables the identification of work situations that are likely to generate high levels of stress at the individual and unit levels. For future studies, this tool will enable the implementation of targeted corrective actions on which intervention research can be based. It also enables national and international comparisons of stressors' impact.
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http://dx.doi.org/10.1186/s13613-021-00846-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036172PMC
April 2021

Renal dysfunction improves risk stratification and may call for a change in the management of intermediate- and high-risk acute pulmonary embolism: results from a multicenter cohort study with external validation.

Crit Care 2021 02 9;25(1):57. Epub 2021 Feb 9.

Department of Cardiology, University Hospital Jean Minjoz, 3 Boulevard Fleming, 25000, Besançon, France.

Background: Renal dysfunction influences outcomes after pulmonary embolism (PE). We aimed to determine the incremental value of adding renal dysfunction, defined by estimated glomerular filtration rate (eGFR), on top of the European Society of Cardiology (ESC) prognostic model, for the prediction of 30-day mortality in acute PE patients, which in turn could lead to the optimization of acute PE management.

Methods: We performed a multicenter, non-interventional retrospective post hoc analysis based on a prospectively collected cohort including consecutive confirmed acute PE stratified per ESC guidelines. We first identified which of three eGFR formulae most accurately predicted death. Changes in global model fit, discrimination, calibration and reclassification parameters were evaluated with the addition of eGFR to the prognostic model.

Results: Among 1943 patients (mean age 67.3 (17.1), 50.4% women), 107 (5.5%) had died at 30 days. The 4-variable Modification of Diet in Renal Disease (eGFR) formula predicted death most accurately. In total, 477 patients (24.5%) had eGFR < 60 ml/min. Observed mortality was higher for intermediate-low-risk and high-risk PE in patients with versus without renal dysfunction. The addition of eGFR information improved model fit, discriminatory capacity, and calibration of the ESC model. Reclassification parameters were significantly increased, yielding 18% reclassification of predicted mortality (p < 0.001). Predicted mortality reclassifications across risk categories were as follows: 63.1% from intermediate-low risk to eGFR-defined intermediate-high risk, 15.8% from intermediate-high risk to eGFR-defined intermediate-low risk, and 21.0% from intermediate-high risk to eGFR-defined high risk. External validation in a cohort of 14,234 eligible patients from the RIETE registry confirmed our findings with a significant improvement of Harrell's C index and reclassification parameters.

Conclusion: The addition of eGFR-derived renal dysfunction on top of the prognostic algorithm led to risk reclassification within the intermediate- and high-risk PE categories. The impact of risk stratification integrating renal dysfunction on therapeutic management for acute PE requires further studies.
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http://dx.doi.org/10.1186/s13054-021-03458-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874488PMC
February 2021

Semi-elemental versus polymeric formula for enteral nutrition in brain-injured critically ill patients: a randomized trial.

Crit Care 2021 01 20;25(1):31. Epub 2021 Jan 20.

Department of Anesthesiology and Intensive Care Medicine, University Hospital of Besancon, 3 bvd Alexander Fleming, 25000, Besancon, France.

Background: The properties of semi-elemental enteral nutrition might theoretically improve gastrointestinal tolerance in brain-injured patients, known to suffer gastroparesis. The purpose of this study was to compare the efficacy and tolerance of a semi-elemental versus a polymeric formula for enteral nutrition (EN) in brain-injured critically ill patients.

Methods: Prospective, randomized study including brain-injured adult patients [Glasgow Coma Scale (GCS) ≤ 8] with an expected duration of mechanical ventilation > 48 h.

Intervention: an enteral semi-elemental (SE group) or polymeric (P group) formula. EN was started within 36 h after admission to the intensive care unit and was delivered according to a standardized nurse-driven protocol. The primary endpoint was the percentage of patients who received both 60% of the daily energy goal at 3 days and 100% of the daily energy goal at 5 days after inclusion. Tolerance of EN was assessed by the rate of gastroparesis, vomiting and diarrhea.

Results: Respectively, 100 and 95 patients were analyzed in the SE and P groups: Age (57[44-65] versus 55[40-65] years) and GCS (6[3-7] versus 5[3-7]) did not differ between groups. The percentage of patients achieving the primary endpoint was similar (46% and 48%, respectively; relative risk (RR) [95% confidence interval (CI)] = 1.05 (0.78-1.42); p = 0.73). The mean daily energy intake was, respectively, 20.2 ± 6.3 versus 21.0 ± 6.5 kcal/kg/day (p = 0.42). Protein intakes were 1.3 ± 0.4 versus 1.1 ± 0.3 g/kg/day (p < 0.0001). Respectively, 18% versus 12% patients presented gastroparesis (p = 0.21), and 16% versus 8% patients suffered from diarrhea (p = 0.11). No patient presented vomiting in either group.

Conclusion: Semi-elemental compared to polymeric formula did not improve daily energy intake or gastrointestinal tolerance of enteral nutrition.

Trial Registration: EudraCT/ID-RCB 2012-A00078-35 (registered January 17, 2012).
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http://dx.doi.org/10.1186/s13054-020-03456-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818740PMC
January 2021

Processing methods and storage duration impact extracellular vesicle counts in red blood cell units.

Blood Adv 2020 11;4(21):5527-5539

University Bourgogne Franche-Comté, INSERM, Etablissement Français du sang Bourgogne Franche Comté, Unité Mixte de Recherche 1098, Interactions Hôte-Greffon-Tumeur, Ingénierie Cellulaire et Génique, Besançon, France.

Extracellular vesicles (EVs) are active components of red blood cell (RBC) concentrates and may be associated with beneficial and adverse effects of transfusion. Elucidating controllable factors associated with EV release in RBC products is thus important to better manage the quality and properties of RBC units. Erythrocyte-derived EVs (EEVs) and platelet-derived EVs (PEVs) were counted in 1226 RBC units (administered to 280 patients) using a standardized cytometry-based method. EV size and CD47 and annexin V expression were also measured. The effects of donor characteristics, processing methods, and storage duration on EV counts were analyzed by using standard comparison tests, and analysis of covariance was used to determine factors independently associated with EV counts. PEV as well as EEV counts were higher in whole-blood-filtered RBC units compared with RBC-filtered units; PEV counts were associated with filter type (higher with filters associated with higher residual platelets), and CD47 expression was higher on EEVs in RBC units stored longer. Multivariate analysis showed that EEV counts were strongly associated with filter type (P < .0001), preparation, and storage time (+25.4 EEV/µL per day [P = .01] and +42.4 EEV/µL per day [P < .0001], respectively). The only independent factor associated with PEV counts was the residual platelet count in the unit (+67.1 PEV/µL; P < .0001). Overall, processing methods have an impact on EV counts and characteristics, leading to large variations in EV quantities transfused into patients. RBC unit processing methods might be standardized to control the EV content of RBC units if any impacts on patient outcomes can be confirmed. The IMIB (Impact of Microparticles in Blood) study is ancillary to the French ABLE (Age of Transfused Blood in Critically Ill Adults) trial (ISRCTN44878718).
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http://dx.doi.org/10.1182/bloodadvances.2020001658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656935PMC
November 2020

Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome: Possible Late Indication for Coronavirus Disease 2019?

Crit Care Explor 2020 Oct 6;2(10):e0240. Epub 2020 Oct 6.

Service de Réanimation médicale, Centre Hospitalier Universitaire Besançon, Besançon, France.

Background: There is now substantial evidence to support venovenous extracorporeal membrane oxygenation efficacy and safety for patients with severe acute respiratory distress syndrome. However, recent guidelines recommend against the initiation of extracorporeal membrane oxygenation in patients with mechanical ventilation for coronavirus disease 2019 severe acute respiratory distress syndrome for greater than 7-10 days.

Case Summary: We report the case of a patient with coronavirus disease 2019 severe acute respiratory distress syndrome with successful late venovenous extracorporeal membrane oxygenation initiation after 20 days of mechanical ventilation. Respiratory compliance, arterial blood gases, and radiological lesions improved progressively under venovenous extracorporeal membrane oxygenation and ultraprotective ventilation. The patient was discharged from ICU.

Conclusions: As coronavirus disease 2019 is a new and incompletely understood entity, we believe that late extracorporeal membrane oxygenation may be considered in selected patients as a bridge to recovery. Further prospective studies are, however, needed.
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http://dx.doi.org/10.1097/CCE.0000000000000240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540917PMC
October 2020

Early prescription of direct oral anticoagulant for the treatment of intermediate-high risk pulmonary embolism: a multi-center, observational cohort study.

Thromb Res 2020 12 8;196:476-482. Epub 2020 Oct 8.

Department of Cardiology, EA3920, University Hospital Besançon, Boulevard Fleming, 25030 Besançon, France.

Objectives: The safety and efficacy of direct oral anticoagulants (DOACs) in intermediate-high risk pulmonary embolism (PE) are unknown. The aims of the present study were to describe outcomes of patients receiving early apixaban or rivaroxaban prescription rather than the recommended delayed prescription strategy.

Methods: Retrospective post-hoc analysis based on prospectively collected data from a multicenter cohort including all consecutive PE patients stratified as intermediate-high risk. Group definitions were: early group with DOAC prescription <72 h after admission; delayed group with DOAC prescription between 72 h and discharge. The 30-day primary efficacy outcome was a clinical composite of all-cause death and hemodynamic decompensation. The 30-day primary safety outcome was major bleeding.

Results: Among 2411 patients admitted with PE, 302 were treated with a DOAC for an intermediate-high risk PE: 34.2% in the early group and 65.9% in the delayed group. The primary outcome occurred in 4.8% (including 1 death and 4 hemodynamic decompensations) in the early DOAC group and in 9.0% in the delayed DOAC group (OR, 0.44, 95% CI 0.15-1.30). The rate of major bleeding did not differ between groups (OR, 0.99; 95% CI 0.45-2.18). The length of stay was numerically shorter in the early group whereas the other outcomes did not differ significantly.

Conclusion: The rate of 30-day outcomes was low in patients receiving a DOAC earlier after admission. Patients in the early DOAC group had a numerically shorter length of stay, with similarly low rates of death and bleeding, and similar RV function recovery compared to the delayed strategy.
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http://dx.doi.org/10.1016/j.thromres.2020.10.003DOI Listing
December 2020

Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients.

Eur Respir J 2020 10 22;56(4). Epub 2020 Oct 22.

Dept of Cardiology, University Hospital, Besançon, France.

Background: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.

Methods: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates.

Results: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL was associated with a 17-fold increase in the adjusted risk of PE.

Conclusion: Elevated D-dimers (>2590 ng·mL) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.
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http://dx.doi.org/10.1183/13993003.01811-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487272PMC
October 2020

COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity.

J Infect 2021 02 25;82(2):282-327. Epub 2020 Aug 25.

Department of Infectious Disease, University Hospital of Besançon, F-25000 Besançon, France; UMR-CNRS 6249 Chrono-Environnement, Université Bourgogne Franche-Comté, F-25000 Besançon, France. Electronic address:

Adaptive Immune responses generated by SARS-CoV-2 virus in convalescent patients according to disease severity remain poorly characterized. To this end, we designed a prospective study (NCT04365322) that included 60 COVID-19 convalescent patients (1-month post infection) in two cohorts respectively entitled mild illness and severe pneumonia. The monitoring of peripheral immune responses was performed using IFNᵧ ELISpot assay. The serology index of each patient was investigated at the same time. Patients with severe pneumonia were older and had more comorbidities than patients with mild illness. T-cell responses in term of frequency and intensity were clearly distinct between mild illness and severe pneumonia patients. Furthermore, our results demonstrated that recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses (Cytomegalovirus, Epstein-Barr-virus and Flu-virus). The presence of potent adaptive immunity even in patients who underwent severe pneumonia sustain the rationale for the development of protective therapeutics against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jinf.2020.08.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445469PMC
February 2021

ECCOR therapy in the ICU: consensus of a European round table meeting.

Crit Care 2020 08 7;24(1):490. Epub 2020 Aug 7.

Baxter, Baxter Deutschland GmbH, Unterschleissheim, Germany.

Background: With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO removal (ECCOR). However, current evidence in these indications is limited. A European ECCOR Expert Round Table Meeting was convened to further explore the potential for this treatment approach.

Methods: A modified Delphi-based method was used to collate European experts' views to better understand how ECCOR therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus.

Results: Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCOR or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCOR therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCOR therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO levels. Driving pressure (≥ 14 cmHO) followed by plateau pressure (P; ≥ 25 cmHO) was considered the most important criteria for ECCOR initiation. Key treatment targets for patients with ARDS undergoing ECCOR included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmHO) and P (< 25 cmHO). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO and no decrease in respiratory rate were key criteria for initiating ECCOR therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30-7.35), respiratory rate (< 20-25 breaths/min), decrease of PaCO (by 10-20%), weaning from NIV, decrease in HCO and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group.

Conclusions: Insights from this group of experienced physicians suggest that ECCOR therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.
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http://dx.doi.org/10.1186/s13054-020-03210-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412288PMC
August 2020

Prone Positioning for Severe Acute Respiratory Distress Syndrome in COVID-19 Patients by a Dedicated Team: A Safe and Pragmatic Reallocation of Medical and Surgical Work Force in Response to the Outbreak.

Ann Surg 2020 12;272(6):e311-e315

Department of Digestive Surgical Oncology - Liver Transplant Unit, University Hospital of Besançon, Besançon, France.

Objective: The aim of this study was to define whether rapidly reallocating health care workers not experienced with PP for performing PP in ICU is feasible and safe.

Summary Background Data: In the setting of severe acute respiratory distress syndrome (ARDS), the use of prone and supine positioning procedures (PP) has been associated with improved oxygenation resulting in decreased mortality. Nevertheless, applying PP is time consuming for ICU staffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitted COVID-19 patients with severe ARDS.

Methods: This prospective cohort study conducted at a single regional university hospital between March 27 and April 15, 2020. Among 117 patients admitted to ICU, 67 patients (57.3%) presented with proven SARS-CoV-2 infection with severe ARDS requiring PP. After accelerated simulation training, 109 volunteers including surgeons, physicians, nurses and physiotherapists, multiple dedicated teams performed daily multiple PP following a systematic checklist. Patient demographics and PP data were collected. Patient safety and health care workers safety were assessed.

Results: Among 117 patients admitted to ICU, 67 patients (57.3%) required PP. Overall, 53 (79%) were male, with a median age of 68.5 years and median body mass index of 29.3 kg/m. A total of 384 PP were performed. Overall, complication occurred in 34 PP (8.8%) and led to PP cancelation in 4 patients (1%). Regarding health care workers safety, four health care workers presented with potential COVID-19 related symptoms and none was positive.

Conclusions: To overcome the surge of critically ill COVID-19 patients, reallocating health care workers to targeted medical tasks beyond their respective expertise such as PP was safe.
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http://dx.doi.org/10.1097/SLA.0000000000004265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668324PMC
December 2020

Oxygen Therapy in the ICU. Reply.

N Engl J Med 2020 06;382(26):2578-2579

University Hospital Jean Minjoz, Besançon, France

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http://dx.doi.org/10.1056/NEJMc2009489DOI Listing
June 2020

Metaphor use in the ICU: rigor with words!

Intensive Care Med 2020 11 18;46(11):2126-2127. Epub 2020 Jun 18.

Intensive Care Unit, Besançon University Hospital, Besançon, France.

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http://dx.doi.org/10.1007/s00134-020-06156-6DOI Listing
November 2020

Initial pH and shockable rhythm are associated with favorable neurological outcome in cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation.

J Thorac Dis 2020 Mar;12(3):849-857

Medical Intensive Care Unit, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Clayton, Australia.

Background: There is uncertainty about best selection criteria for extracorporeal cardiopulmonary resuscitation (eCPR) in the setting of refractory cardiac arrest. We aimed to identify factors associated with a favorable neurological outcome, and to build a score calculable at the time of ECMO insertion predicting the prognosis.

Methods: Retrospective analysis of all patients who underwent eCPR between 2010 and 2017 in a single university hospital. Primary end point was survival with favorable neurological outcome at intensive care unit (ICU) discharge defined as a Cerebral Performance Category of 1 or 2.

Results: Overall low-flow time of the 113 included patients was 84 [55-122] minutes. Eighteen patients (16%) survived with a favorable neurological outcome. By multivariate logistic regression analysis, initial shockable rhythm, and arterial blood pH at the time of eCPR implantation ≥7.0, were independent predictors of survival with favorable neurological outcome. All of the patients presenting with both non-shockable rhythm and pH <7.0 at the time of eCPR implantation died in the ICU.

Conclusions: At the time of eCPR start, only initial shockable rhythm and arterial pH ≥7.0 predicted neurological outcome. A selection of the patients who might benefit from eCPR, based upon initial rhythm and arterial pH rather than on low flow time, should be further evaluated.
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http://dx.doi.org/10.21037/jtd.2019.12.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139075PMC
March 2020

Scales Used to Measure Job Stressors in Intensive Care Units: Are They Relevant and Reliable? A Systematic Review.

Front Psychol 2020 12;11:245. Epub 2020 Mar 12.

Medical Intensive Care Unit, University Hospital of Besançon, Besançon, France.

Many studies have been conducted in intensive care units (ICUs) to identify the stress factors involved in the health of professionals and the quality and safety of care. The objectives are to identify the psychometric scales used in these studies to measure stressors and to assess their relevance and validity/reliability. All peer-reviewed full-text articles published in English between 1997 and 2016 and focusing on an empirical quantitative study of job stressors were identified through searches on seven databases and editorial portals. From the 102 studies analyzed, we identified 59 different scales: 17 "all settings scales" (16 validated scales), 20 "healthcare settings scales" (13 validated scales), and 22 "ICU settings scales" (two validated scales). All these scales used measured stressors from at least one of the following eight broad categories: High job demands, Problematic relationships with other professionals, Lack of control over work situations and career, Lack of organizational resources, Problematic situations with users and relatives, Dealing with ethical- and moral-related situations, Risk management issues, and Disadvantages in comparison to other occupational situations. The "all settings scales" and "healthcare settings scales," the most often validated, did not measure, or only slightly measured, the stressors most specific to ICUs. Where these were taken into account, the authors were forced to develop their own tools or modify existing scales without testing the validity of the tool used. This review highlights the lack of a tool that meets both the criteria of validity and relevance with regard to the specificity of work in ICUs. Future research must focus on developing reliable/valid tools covering all types of relevant stressors to ensure the quality of the studies carried out in this field.
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http://dx.doi.org/10.3389/fpsyg.2020.00245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080865PMC
March 2020

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

N Engl J Med 2020 03;382(11):999-1008

From the Medical Intensive Care Unit (L.B., H.W., L.V., G.C.), the Anesthesia and Intensive Care Unit (L.B., S.P.-F.), Unité de Méthodologie, INSERM Clinical Investigation Center 1431, University Hospital (F. Mauny, M.P.), and Research Unit EA3920, Université de Franche Comté (L.B., H.W. S.P.-F., G.C.), Besançon, the Medical Intensive Care Unit, University Hospital of Angers, Angers (P.A.), the Intensive Care Unit, General Hospital of Avignon, Avignon (F. Montini), the Intensive Care Unit, General Hospital of Nord Franche-Comté, Trévenans (J.B.), the Medical Intensive Care Unit (J.-P.Q.) and the Anesthesia and Intensive Care Unit (B.B.), University Hospital of Dijon, Dijon, the Intensive Care Unit, General Hospital of Metz-Thionville, Metz (G.L.), the Medical Intensive Care Unit (B.S.) and the Anesthesia and Intensive Care Unit (J.-M.C.), University Hospital of Clermont-Ferrand, Clermont-Ferrand, the Anesthesia and Intensive Care Unit, University Hospital of Strasbourg, Strasbourg (O.C., J.P.), and the Medical Intensive Care Unit, University Hospital of Nancy, Nancy (B.L.) - all in France; and the Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia (G.C.).

Background: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS.

Methods: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo], 88 to 92%) or liberal oxygen therapy (target Pao, 90 to 105 mm Hg; Spo, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days.

Results: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group.

Conclusions: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO ClinicalTrials.gov number, NCT02713451.).
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http://dx.doi.org/10.1056/NEJMoa1916431DOI Listing
March 2020

Ventilation feedback device for manual ventilation in simulated respiratory arrest: a crossover manikin study.

Scand J Trauma Resusc Emerg Med 2019 Oct 22;27(1):93. Epub 2019 Oct 22.

Emergency Medicine Physician, Department of Emergency Medicine and Critical Care, Besançon University Hospital, Besançon, France.

Background: Studies have shown that providing adequate ventilation during CPR is essential. While hypoventilation is often feared by most caregivers on the scene, the most critical problem remains hyperventilation. We developed a Ventilation Feedback Device (VFD) for manual ventilation which monitors ventilatory parameters and provides direct feedback about ventilation quality to the rescuer. This study aims to compare the quality of conventional manual ventilation to ventilation with VFD on a simulated respiratory arrest patient.

Methods: Forty healthcare providers were enrolled and instructed to ventilate a manikin simulating respiratory arrest. Participants were instructed to ventilate the manikin for 5 min with and without the VFD in random order. They were divided in two groups of 20 people, one group ventilating through a mask and the other through an endotracheal tube.

Results: Ventilation with the VFD improved from 15 to 90% (p < 0.001) with the mask and from 15 to 85% (p < 0.001) with the endotracheal tube (ETT) by significantly reducing the proportion of hyperventilation. The mean ventilation rates and tidal volumes were in the recommended ranges in respectively 100% with the mask and 97.5% of participants with the ETT when using the VFD.

Conclusion: VFD improves the performance of manual ventilation by over 70% in different simulated scenarios. By providing the rescuer direct feedback and analysis of ventilatory parameters, this device can significantly improve ventilation while performing CPR and thus save lives.
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http://dx.doi.org/10.1186/s13049-019-0674-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805533PMC
October 2019

Air in the Heart? Check the Liver.

Am J Respir Crit Care Med 2020 Apr;201(8):995

Medical Intensive Care Unit and.

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http://dx.doi.org/10.1164/rccm.201908-1507IMDOI Listing
April 2020

The effect visiting relatives in the adult ICU has on children.

Intensive Care Med 2019 10 22;45(10):1490-1492. Epub 2019 Jul 22.

Medical Intensive Care Unit, University Hospital of Besançon, Besançon, France.

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http://dx.doi.org/10.1007/s00134-019-05690-2DOI Listing
October 2019

Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial.

Ann Intensive Care 2019 Jul 1;9(1):75. Epub 2019 Jul 1.

CH de Bourg en Bresse, Service de Réanimation polyvalente, 01000, Bourg en Bresse, France.

Background: Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial.

Methods: In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality.

Results: Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups.

Conclusions: In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.
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http://dx.doi.org/10.1186/s13613-019-0553-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603108PMC
July 2019

Echography of Hepatic Venous Gas. The Rhythmic Movement.

Am J Respir Crit Care Med 2019 09;200(6):e44

Medical Intensive Care Unit, Besançon University Hospital, Besançon, France; and.

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http://dx.doi.org/10.1164/rccm.201901-0087IMDOI Listing
September 2019

Effect of age of transfused red blood cells on neurologic outcome following traumatic brain injury (ABLE-tbi Study): a nested study of the Age of Blood Evaluation (ABLE) trial.

Can J Anaesth 2019 06 26;66(6):696-705. Epub 2019 Feb 26.

CHU de Québec - Université Laval Research Centre, Population Health and Optimal Health Practices Research Unit, Trauma - Emergency - Critical Care Medicine, Université Laval, Quebec City, QC, Canada.

Background: Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells.

Methods: Our study aimed to ascertain whether the administration of fresh red blood cells (seven days or less) results in a better neurologic outcome compared with standard red blood cells in critically ill patients with traumatic brain injury requiring transfusion. The Age of Blood Evaluation in traumatic brain injury (ABLE-tbi) study was a nested study within the ABLE study (ISRCTN44878718). Our primary outcome was the extended Glasgow Outcome Scale (GOSe) at six months.

Results: In the ABLE study, 217 subjects suffered a traumatic brain injury: 110 in the fresh group, and 107 in the standard group. In the fresh group, 68 (73.1%) of the patients had an unfavourable neurologic outcome (GOSe ≤ 4) compared with 60 (64.5%) in the standard group (P = 0.21). Using a sliding dichotomy approach, we observed no overall effect of fresh red blood cells on neurologic outcome (odds ratio [OR], 1.34; 95% confidence interval [CI], 0.72 to 2.50; P = 0.35) but observed differences across prognostic bands with a decreased odds of unfavourable outcome in patients with the best prognosis at baseline (OR, 0.33; 95% CI, 0.11 to 0.96; P = 0.04) but an increased odds in those with intermediate and worst baseline prognosis (OR, 5.88; 95% CI,1.66 to 20.81; P = 0.006; and OR, 1.67; 95% CI, 0.53 to 5.30; P = 0.38, respectively).

Conclusion: Overall, transfusion of fresh red blood cells was not associated with a better neurologic outcome at six months in critically ill patients with traumatic brain injury. Nevertheless, we cannot exclude a differential effect according to the patient baseline prognosis.

Trial Registration: ABLE study (ISRCTN44878718); registered 22 August, 2008.
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http://dx.doi.org/10.1007/s12630-019-01326-7DOI Listing
June 2019

Ultrasound-guided vessel puncture: calling for Pythagoras' help.

Crit Care 2018 11 8;22(1):292. Epub 2018 Nov 8.

Medical Intensive Care Unit, Besançon University Hospital, Besançon, France.

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http://dx.doi.org/10.1186/s13054-018-2228-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225660PMC
November 2018

Response to Glowka et al.

J Crit Care 2018 12 23;48:473. Epub 2018 Sep 23.

Medical Intensive Care Unit, University Hospital of Besancon, France.

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http://dx.doi.org/10.1016/j.jcrc.2018.09.027DOI Listing
December 2018

Malposition of the Extracorporeal Membrane Oxygenation Venous Cannula in an Accessory Hepatic Vein.

J Extra Corpor Technol 2018 09;50(3):167-169

Medical Intensive Care Unit.

We report a case of a refractory cardiogenic shock secondary to myocardial infarction in a 70-year-old patient requiring femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). At initial transesophageal echocardiography, the venous cannula tip was seen in the inferior vena cava (IVC), but not in right atrium. On day 8, ultrasonic examination identified that the end of the venous cannula was in the hepatic vein (HV). Despite such malposition, no disturbance in extracorporeal membrane oxygenation (ECMO) venous return was observed. Moving or replacing the cannula was considered a high-risk maneuver potentially resulting in hepatic laceration with hemoperitoneum. Because of adequate venous drainage, allowing sufficient blood flow, venous cannula repositioning was delayed until day 10, when a ventricular defect was repaired and ECMO was weaned off. At the time of VA-ECMO implantation, the venous cannula has to be positioned in the right atrium using real time echo monitoring. Visualization of the guide wire in the IVC but not in the right atrium is insufficient to ensure appropriate venous cannula positioning. Indeed, either accidental catheterization or cannula migration into the HV is possible during ECMO. Health care professionals dealing with ECMO have to be aware of this possible malposition, to correct it and prevent insufficient venous drainage or traumatic complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146273PMC
September 2018
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