Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Ageing of the postural vertical.

International audienceA postural vertical (PV) tilted backward has been put forward as a reason explaining the backward disequilibrium often observed in elderly fallers. This raises the question of a possible ageing process of the PV involving a backward tilt of verticality perception increasing with age. We have explored this hypothesis by measuring PV in pitch using the wheel paradigm in 87 healthy subjects aged from 20 to 97 years. The possibility that this physiological ageing accelerated in the second part of life was also analysed. Two indices were calculated: the mean orientation (PV-orient) and the dispersion (PV-uncert). The correlation between age and PV-orient was r = -0.2 (p < 0.05). Added to the fact that PV was twice as shifted backward in the 38 seniors over 50 years (-1.15 degrees +/- 1.40 degrees ) as in the 49 young adults under 50 years (-0.45 degrees +/- 0.97 degrees ; t = 2.75, p < 0.01), this indicates the existence of a physiological ageing process on the direction perceived as vertical by the whole body, with a slight backward shift of PV throughout the life span. The correlation between age and PV-uncert was r = 0.35 (p < 0.001) in all subjects and r = 0.59 (p < 0.001) in seniors. This indicates that subjects get less and less accurate in their perception of the postural vertical with age, especially very old subjects who show great uncertainty in determining with their body the direction of the vertical. Taken together, these findings indicate that the internal model of verticality is less robust in elderly people. This may play a part in their postural decline

Achilles tendon vibration shifts the center of pressure backward in standing and forward in sitting in young subjects.

International audienceOBJECTIVE: An Achilles tendon (AT) vibration is known to disrupt the postural control in standing ("vibration-induced falling", VIF) and to backward tilt the postural vertical in restrained sitting position, suggesting a link between AT vibration and internal representations involved in postural control. A recalibration of some troubles in body orientation by oriented sensory manipulations could be of great clinical interest. In order to use the VIF paradigm in a procedure suitable for a rehabilitation context, AT vibration deserves to be more investigated in sitting, for security reasons, and first in young participants. METHOD: In 12 healthy participants (6 men/6 women; 23.3±1.9years), posturographic data to AT vibrations (85Hz) were recorded over 30s standing and 40s sitting trials. RESULTS: Surprisingly, four types of differences were found between standing and sitting AT vibrations: presence/absence of VIF and kinesthetic illusion, opposite directions of the centre of foot pressure (CoP) displacements, different temporal profiles. In standing: VIF without kinesthetic illusion, rapid backward shift of CoP with a peak of -54.6±11.3mm (with respect to baseline P<0.001) 2.8±0.2s after vibration onset. In sitting: surprising systematic forward shift of the CoP throughout the duration of AT vibration with a maximum of 27.9±18.9mm (P<0.05 with respect to the baseline) 19.6±0.3s after vibration onset, associated with a kinesthetic illusion in most subjects. CONCLUSION: The present study invalidates our idea to extend in sitting the VIF paradigm but the unexpected results open a new window about the basic mechanisms underlying muscle vibration effects

Posturography in patients with stroke: estimating the percentage of body weight on each foot from a single force platform.

International audienceBACKGROUND AND PURPOSE: Posturography in patients with stroke is widely based on the use of a single force platform and the weightbearing asymmetry quantified from the lateral shift of the center of pressure toward the sound leg. Because the percentage of body weight on each side is a more concrete variable, the present study analyzed the possibility of inferring percentage of body weight from center of pressure. METHODS: Forty-five hemiparetic subjects were asked to stand on a dual platform in a standardized position 3 months after a hemispheric stroke. First, the relationship between the %BW on each foot and the lateral shift of center of pressure was established. Second, the model was tested with a healthy subject standing on a single force platform. RESULTS: The percentage of body weight may be simply modeled from the center of pressure shift, a center of pressure displacement of 10 mm corresponding to a 5% increase in body weight on this side (r=0.97, P<0.001). This linear model is reliable, accurate, and may be generalized to other stand widths. CONCLUSIONS: This finding should be useful for constructors and users of single force platforms, especially those involved in posturographic assessments of asymmetric conditions such as hemiparesis

Contribution of each lower limb to upright standing in stroke patients.

International audienceBACKGROUND AND PURPOSE: To analyze the postural behavior of standing stroke patients: (1) To differentiate between postural impairment attributable to the neurological condition (deficits attributable to the cerebral lesion) and postural impairment attributable to new mechanical constraints caused by body weight asymmetry; (2) To assess the involvement of each limb in the postural impairment; (3) To better understand which clinical deficits underlie the postural impairment. METHODS: The posturographic characteristics of each limb in 41 stroke patients (first hemispheric stroke: 16 left, 25 right cerebral lesions) required to stand in their preferred posture were compared to those in 40 matched healthy individuals required to stand asymmetrically. RESULTS: Compared to normal individuals in a similar asymmetrical posture, stroke patients were more unstable. The weight bearing asymmetry and the lateral postural instability were mainly related to spatial neglect. The paretic limb was unable to bring into play a normal longitudinal pattern of the center of pressure, which reflects an impaired stabilization control. Overall postural instability occurred when the strong limb was unable to compensate for the postural impairment of the paretic limb. CONCLUSIONS: The weight bearing asymmetry of standing stroke patients is not the primary cause of their postural imbalance, which is rather the consequence of impaired control of postural stabilization involving both limbs. Weight bearing asymmetry may not be the principle target of rehabilitation programs aiming at restoring standing balance after stroke. Instead it is suggested that more account should be taken of the compensatory role of the strong limb

Vascular endothelial growth factor, tissue factor, coagulation and fibrinolysis markers in slow-flow vascular malformations: a prospective study of treatment with sirolimus

International audienceSlow-flow vascular malformations (VMs), especially those with venous components, can be complicated by localized intravascular coagulopathy (LIC), responsible for pain and impaired quality of life. Several studies have shown the effectiveness of mTOR inhibitors (especially sirolimus) on slow-flow VMs but its effect on coagulation has been poorly studied, especially in children. Our study shows that venous and combined VMs are associated with coagulation abnormalities and provides novel evidence that sirolimus improves coagulopathy in venous malformations. However we did not clearly evidence predictive biomarkers of response to sirolimus but this is the first study attempting to highlight predictive markers of response to sirolimus

Sirolimus (Rapamycin) for Slow-Flow Malformations in Children

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Sirolimus (rapamycine) pour le traitement des malformations vasculaires de bas débit chez l’enfant : essai randomisé multicentrique ouverte avec une phase observationnelle préalable (PERFORMUS)

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