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1.
Innovation in Aging ; 5:590-591, 2021.
Article in English | Web of Science | ID: covidwho-2011840
2.
Innovation in Aging ; 5:73-73, 2021.
Article in English | Web of Science | ID: covidwho-2011082
3.
Fundamental and Clinical Pharmacology ; 36:49-50, 2022.
Article in English | EMBASE | ID: covidwho-1968107

ABSTRACT

Introduction: Acute Respiratory Distress Syndrome (ARDS) became a leading cause of ICU admission since the COVID-19 outbreak. Refractory ARDS can benefit from Veno-Venous Extra Corporeal Membrane Oxygenation (VV ECMO). Amiodarone is used for treating cardiac arrhythmias and shockable cardiac arrest during cardiopulmonary resuscitation (CPR). Data about amiodarone under VV ECMO are still lacking. In a previous work led on a model of ARDS in pigs ongoing CPR, we showed a pharmacokinetics impairment of amiodarone under VV ECMO. We aimed to establish a PK modelling of amiodarone concentrations. Material and methods: Nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Impact of VV ECMO on amiodarone pharmacokinetic profile were investigated. Using our final model, different dosing schemes for amiodarone (10 000 Monte Carlo simulations) were simulated in animals on ECMO VV. Results: A two-compartment model with first-order absorption and elimination was able to accurately describe amiodarone plasma concentrations. Interindividual variability was retained for clearance and central volume of distribution. Amiodarone PK parameters were influenced by the ECMO covariable. All parameters were well estimated. Goodness of fit plots comforted the accuracy of the model. Predicted-corrected visual predictive check of the final model was satisfactory. Simulated amiodarone exposure showed that amiodarone 600 mg bolus is required under VV ECMO to achieve similar AUC observed in the control group. Discussion/Conclusion: In our model of ARDS in pigs with cardiac arrest and benefiting from CPR and VV ECMO, a two-compartment model with first-order absorption and elimination was able to accurately describe amiodarone plasma concentrations. VV ECMO significantly modified both central distribution volume and amiodarone clearance. From Monte-Carlo simulation, we showed that a 2-fold increase of amiodarone doses should be considered to reach efficient drug exposure under VV ECMO.

4.
Cahiers de Psychologie Clinique ; 58(1):303-305, 2022.
Article in French | Scopus | ID: covidwho-1875864
5.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-329336

ABSTRACT

A recent estimate suggests that one in five deaths globally are associated with sepsis 1 . To date, no targeted treatment is available for this syndrome, likely due to substantial patient heterogeneity 2,3 and our lack of insight into sepsis immunopathology 4 . These issues are highlighted by the current COVID-19 pandemic, wherein many clinical manifestations of severe SARS-CoV-2 infection parallel bacterial sepsis 5-8 . We previously reported an expanded CD14+ monocyte state, MS1, in patients with bacterial sepsis or non-infectious critical illness, and validated its expansion in sepsis across thousands of patients using public transcriptomic data 9 . Despite its marked expansion in the circulation of bacterial sepsis patients, its relevance to viral sepsis and association with disease outcomes have not been examined. In addition, the ontogeny and function of this monocyte state remain poorly characterized. Using public transcriptomic data, we show that the expression of the MS1 program is associated with sepsis mortality and is up-regulated in monocytes from patients with severe COVID-19. We found that blood plasma from bacterial sepsis or COVID-19 patients with severe disease induces emergency myelopoiesis and expression of the MS1 program, which are dependent on the cytokines IL-6 and IL-10. Finally, we demonstrate that MS1 cells are broadly immunosuppressive, similar to monocytic myeloid-derived suppressor cells (MDSCs), and have decreased responsiveness to stimulation. Our findings highlight the utility of regulatory myeloid cells in sepsis prognosis, and the role of systemic cytokines in inducing emergency myelopoiesis during severe bacterial and SARS-CoV-2 infections.

6.
Computer Methods in Biomechanics and Biomedical Engineering ; 24(SUPPL 1):S240-S242, 2021.
Article in English | EMBASE | ID: covidwho-1593656

ABSTRACT

Introduction Musculoskeletal disorders associated with patients care and manipulation are frequent among healthcare workers, due to force exertion and sustained awkward postures (EU Commission 2011, Davis 2015). During the COVID-19 pandemic, intensive care units (ICUs) staffs had to perform prone-positioning (PP) of a large number of intubated patients suffering from Acute Respiratory Distress Syndrome (ARDS) many times a day. PP maneuver consists in repositioning a patient from a supine position (on the back) to a prone position (on the front side), which improves oxygenation and ventilatory mechanisms in ARDS patients (Guérin et al. 2013). PP is a delicate procedure (risk of extubation) which requires the medical staff to remain bent forward for several minutes (Figure 1). This posture result in back loading and in the long-term potential injuries in the low-back. Similar postures are common in industrial tasks, and recently occupational exoskeletons have started to be commercialized to help reduce physical load on workers (DeLooze et al. 2016). Exoskeletons therefore appear as a promising solution to support healthcare workers, though few studies focused on this sector (e.g. Miura et al. 2020;Iishi et al. 2015). But while studies overall agree that back-support exoskeletons, and specifically passive devices, have the potential to reduce lumbar muscle activity in tasks involving trunk bending, the exact efficacy and usability of such devices appear largely device-and task-dependent (Theurel et al. 2019). A preliminary study of our team (Settembre et al. 2020) identified the Laevo passive exoskeleton for lumbar support (Laevo, the Netherlands) as the exoskeleton that best matched the PP maneuver and ICU constraints, among 4 exoskeletons that were available at the time of the test during the COVID-19 first wave. The present study presents a pilot investigation of the biomechanical effects of using the Laevo during PP maneuver. 2. Methods 2.1. Experimental protocol Two healthy volunteers with PP experience performed PP maneuvers both with and without wearing the Laevo, on a patient simulator (manikin) at the Hospital Simulation Center of the University of Lorraine (Figure 1). Each maneuver lasted about 4 min. In a first experiment, the participants were equipped with the Xsens MVN Link inertial motion capture system (capture rate 240 Hz) to record wholebody kinematics. In a subsequent experiment, the participants were equipped with a Delsys Trigno EKG sensor to measure heart rate, and 12 Delsys Trigno sEMG sensors (sampling rate 4370 sa/sec) placed according to the Seniam recommendations bilaterally on the erector spinae longissimus (ESL), erector spinae iliocostalis (ESI), trapezius ascendens (TA), and biceps femoris long head (BF), and laterally on the right rectus abdominis at T10 level (RA), rectus femoris (RF), gluteus maximus (GM) and tibialis anterior (TAL). 2.2. Data analysis In order to analyze the kinematics and dynamics of the maneuver, we replayed the recorded motions in a physics-engine based simulation using a 43 degrees of freedom digital human model (DHM). The recorded motions were retargeted on the DHM directly in the Cartesian space by using a quadratic programming controller (QP) typically used for humanoid robots (Maurice et al. 2019). The QP control directly estimates the joint torques associated with the motion. This method has the advantage to blend the traditional inverse kinematics and inverse dynamics steps into one faster step, since the computation runs in close to real-time. Since we did not have a direct measurement of the support torque provided by the Laevo, we used the empirical calibration curve published by (Koopman et al. 2019) to estimate the lumbar support torque depending on the trunk flexion angle. We used the resulting L5/S1 flexion/extension estimated joint torque as a complement to the physiological measurements obtained with the sEMG. 3. Results and discussion Kinematic results: Using the Laevo did not significantly modify the kinematics of the motion during PP. Specific lly, the profile of the lumbar flexion angle remained overall similar (Figure 2). This result was confirmed by the subjective feedback of the participants who reported that they did not feel the exoskeleton was affecting the way they performed the task. Dynamic results: The median value of the estimated L5/S1 flexion/extension torque decreased by about 12% when using the Laevo (Figure 2). This result agrees with the reduced perceived lumbar effort reported by participants, and is aligned with the 15% reduction observed by (Koopman et al. 2019) in a similar static forward bending task. Yet those results should be considered cautiously, since only the assistive torque of the exoskeleton was modeled, and not the full effect of the load transfer. Physiological results: We did not observe any major change in heart rate when using the Laevo. This might be due to the short duration of the experimental task (4 min). The activity of the back extensor muscles (except ESI) and hip extensor muscles overall decreased when using the Laevo (Table 1). The other recorded muscles remained mostly unaffected by the exoskeleton. Those results are consistent with the perceived reduced effort reported by the participants. 4. Conclusions Our pilot study, though limited to a small number of participants, suggests that using the Laevo could help reduce the musculoskeletal load on the low back during PP maneuver, without causing any significant negative side-effect nor modifying the practice. Following this study, 2 Laevos have been successfully deployed in the ICU of CHRU Nancy and have been used there for the past 6 months. Recording quantitative measurements during this fieldtesting is not possible. However subjective feedback from users is collected through questionnaires and interviews, and will be analyzed in a future study.

7.
J. Am. Oil Chem. Soc. ; 98:83-84, 2021.
Article in English | Web of Science | ID: covidwho-1444945
8.
MEDLINE; 2021.
Preprint in English | MEDLINE | ID: ppcovidwho-290817

ABSTRACT

Neutrophil-mediated secondary tissue injury underlies acute respiratory distress syndrome (ARDS) and progression to multi-organ-failure (MOF) and death, processes linked to severe COVID19. This 'innocent bystander' tissue injury arises in dysregulated hyperinflammatory states from neutrophil functions and neutrophil extracellular traps (NETs) intended to kill pathogens, but injure cells instead, causing MOF. Insufficiency of prior therapeutic approaches suggest need to identify dysregulated neutrophil-subset(s) and induce subset-specific apoptosis critical for neutrophil function-shutdown and clearance. We hypothesized that neutrophils expressing the pro-survival dual endothelin-1/signal peptide receptor, DEspR, are apoptosis-resistant just like DEspR+ cancer cells, hence comprise a consequential pathogenic neutrophil-subset in ARDS and COVID19-ARDS. Here, we report correlation of circulating DEspR+CD11b+ activated neutrophils (DESpR+actNs) and NETosing-neutrophils with severity in ARDS and in COVID19-ARDS, increased DEspR+ neutrophils and monocytes in post-mortem ARDS-patient lung sections, and neutrophil DEspR/ET1 receptor/ligand autocrine loops in severe COVID19. Unlike DEspR[-] neutrophils, ARDS patient DEspR+actNs exhibit apoptosis-resistance, which decreased upon ex vivo treatment with humanized anti-DEspR-IgG4 S228P antibody, hu6g8. Ex vivo live-cell imaging of non-human primate DEspR+actNs showed hu6g8 target-engagement, internalization, and induction of apoptosis. Altogether, data differentiate DEspR+actNs as a targetable neutrophil-subset associated with ARDS and COVID19-ARDS severity, and suggest DEspR-inhibition as a potential therapeutic paradigm. 1-sentence summary: Circulating DEspR+CD11b+ neutrophils and NETosing neutrophils are associated with severity and mortality in ARDS and COVID19-ARDS.

9.
JMV-Journal de Médecine Vasculaire ; 46(5, Supplement):S43, 2021.
Article in English | ScienceDirect | ID: covidwho-1433490

ABSTRACT

L’enzyme de conversion de type 2 ou ACE2 est une enzyme de clairance de l’angiotensine 2 qui clive cette dernière en un peptide (Ang 1-7) dont les effets sont opposés à ceux de l’angiotensine 2 : vasodilatateurs, anti-inflammatoires et anti-fibrosants. ACE2 est surexprimée dans toutes les situations de risque cardiovasculaire élevé : maladies coronaires, insuffisance cardiaque, hypertension, obésité, diabète. Le virus SARS-CoV-2 se lie à l’ACE2 membranaire pour pénétrer dans les cellules qu’il infecte. L’abondance de l’ACE2 chez les malades à risque cardiovasculaire élevé est probablement un facteur d’augmentation du risque d’infection virale. Il existe très peu ou pas de mesures des concentration tissulaire de ACE2 chez l’homme. Encore moins chez des patients recevant un traitement par un bloqueur du système rénine angiotensine. À partir des études expérimentales, on peut avancer que les inhibiteurs de l’enzyme de conversion n’ont semble-t-il pas d’effet sur les concentrations plasmatiques et tissulaires d’ACE2 alors que les bloqueurs des récepteurs de l’angiotensine augmenteraient l’activité de l’ACE2. Enfin, les premiers grands essais cliniques observationnels publiés montrent clairement que les traitements chroniques par des bloqueurs du SRAA n’ont pas d’effet sur l’incidence et la gravité de l’infection virale. Ces traitements ne doivent donc pas être interrompus ni pour prévenir une éventuelle infection par le SARS-CoV-2 ni en cas de survenue avérée de COVID-19.

10.
American Journal of Respiratory and Critical Care Medicine ; 203(9):1, 2021.
Article in English | Web of Science | ID: covidwho-1407100
11.
AHFE Conference on Human Factors and Ergonomics in Healthcare and Medical Devices, 2021 ; 263:88-100, 2021.
Article in English | Scopus | ID: covidwho-1359886

ABSTRACT

We conducted a pilot study to evaluate the potential and feasibility of back-support exoskeletons to help the caregivers in the Intensive Care Unit (ICU) of the University Hospital of Nancy (France) executing Prone Positioning (PP) maneuvers on patients suffering from severe COVID-19-related Acute Respiratory Distress Syndrome. After comparing four commercial exoskeletons, the Laevo passive exoskeleton was selected for use in the ICU in April 2020. The first volunteers using the Laevo reported very positive feedback and reduction of effort, confirmed by EMG and ECG analysis. Laevo has since been used to physically assist during PP in the ICU of the Hospital of Nancy, following the resurgence of COVID-19, with an overall positive feedback. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

12.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277103

ABSTRACT

RATIONALE: COVID-19 activity continues to cause a high disease burden, and hospitals are vulnerable to ventilator scarcity. Crisis standards of care aim to maximize lives saved and to minimize clinician distress from bedside rationing. 26 states have allocation guidelines. 15 use the Sequential Organ Failure Assessment (SOFA) score. SOFA predicts mortality in hospitalized patients and provides objective data to reduce the risk of introducing bias. We use data from the COVID-19 surge in New York City (NYC) to model performance of a protocol based on SOFA scores and NY State guidelines. Although these guidelines were not implemented, we estimate the hypothetical outcomes had they been required. METHODS: This is a chart review of a random sample (205) of all intubated patients (1002) in three NYC hospitals between 25 March 2020 and 29 April 2020. Patients with and without COVID-19 were included. SOFA scores were calculated upon intubation, 48-, and 120-hours post-intubation. We calculated mortality and proportion of patients categorized into four groups: blue (ventilator not offered or removed), red (highest priority), yellow (intermediate priority), and green (weaned or ventilation not indicated) at each interval. RESULTS: 65 (32%) patients survived to discharge (Figure). 117 patients (57%) were categorized blue at least once;28 (24%) of those ultimately survived hospitalization. Patients ever in blue category had higher mortality (76%) compared with those never categorized blue (58%;p<0.01). Of expired patients, 89 (63%) were ever categorized as blue. CONCLUSIONS: Since over half of all patients met exclusion criteria at one or more time points, clinical judgment may still be needed to decide which patients would be excluded first. This re-introduces bias and moral distress;issues effective triage protocols should address. More specific scoring systems, such as 4C mortality score, may improve performance. Alternative strategies including first-come, first-served, randomization, clinician judgement, and triage committees lack empirical data and have ethical shortcomings. Our findings differ from a recent retrospective cohort study, which found few patients outside of the pandemic met New York State guideline blue category criteria among more than 40,000 ICU admissions. Our sample more closely reflects the acuity of pandemic conditions when this allocation guideline would be activated. The data from this preliminary study suggest that the SOFA score offers limited utility in triage, raising the question of whether sufficient ethical justification exists to impose a life-ending decision on a subset of patients to offer potential benefit to a modest number of others.

13.
South African Medical Journal ; 111(6):535-537, 2021.
Article in English | EMBASE | ID: covidwho-1264653

ABSTRACT

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

14.
Thoracic and Cardiovascular Surgeon ; 69(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1240797

ABSTRACT

Objectives: With the occurrence of the COVID-19 pandemic in the year of 2020 the number of patients in need ofintensive care medicine increased dramatically in many countries. Several of them developed an acute respiratory distresssyndrome (ARDS) linked to the COVID-19 infection and many required the use of extracorporeal membrane oxygenation(ECMO). Methods: We are retrospectively reviewing 141 patients who underwent ECMO for severe COVID-19-related ARDS in amulticenter study at 10 European ECMO centers. Result: A total of 141 patients (67.4% male, median age was 55.4 years (interquartile range [IQR]: 44-67.5) were treatedwith ECMO for confirmed (132) or suspected (9) severe COVID-19-related ARDS. Before ECMO, the median SequentialOrgan Failure Assessment (SOFA) score was 9.0 (IQR: 7.0-11.5), median pH was 7.25 (IQR: 7.20-7.30), and medianPaO /FiO ratio was 70 mm Hg (IQR: 60-77). Venovenous ECMO was provided in 130 patients (92%) and venoarterial ECMO in 11 patients (8%) The median duration ofECMO treatment by now was 11 days, IQR: 7-17). At the time of reporting, 71 confirmed COVID-19 patients (53.8%) arealive, of whom 33 (43.4%) are still in the intensive care unit (9 on ECMO, 24 weaned from ECMO and extubated). Overallmortality so far occurred in 62 patients (46.2%). By now advanced age, low arterial pH, and low platelet count before ECMO were independent risk factors for increasedmortality during the intensive care treatment. Conclusion: Despite a substantial overall mortality of over 40%, approximately half of the patients with severe COVID-19-related ARDS, refractory to conventional treatment, may be successfully managed with ECMO therapy.

15.
Sang Thrombose Vaisseaux ; 32(6):260-268, 2020.
Article in French | Scopus | ID: covidwho-1190222

ABSTRACT

Severe acute respiratory syndrome coronavirus 2, which is responsible for the current coronavi-rus disease 2019 pandemic, uses angiotensin-converting enzyme 2 as a gateway into host cells. In this review, we summarized the biology of this enzyme which plays a key role in cardiovascular homeostasis and blood pressure control. Blockers of the renin-angiotensin-aldosterone system modify the expression and activity of angiotensin-converting enzyme 2, possibly in different ways. The effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the expression and enzyme activity of angiotensin-converting enzyme 2 are reviewed, and the consequences of these treatments for the severity of coronavirus disease 2019 infection are discussed. © 2020, John Libbey. All rights reserved.

17.
Southern African Journal of Critical Care ; 36(1):14-17, 2020.
Article | WHO COVID | ID: covidwho-725231

ABSTRACT

The COVID-19 pandemic has placed healthcare resources around the world under immense pressure. South Africa, given the condition of its healthcare system, is particularly vulnerable. There has been much discussion around rational healthcare utilisation, ranging from diagnostic testing and personal protective equipment to triage and appropriate use of ventilation strategies. There has, however, been little guidance around use of laboratory tests once COVID-19 positive patients have been admitted to hospital. We present a working guide to rational laboratory test use, specifically for COVID-19, among hospitalised patients, including the critically ill. The specific tests, the reasons for testing, their clinical usefulness, timing and frequency are addressed. We also provide a discussion around evidence for the use of these tests from a clinical perspective.

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