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/)

Muscle fiber types identification by synchrotron fluorescence microspectroscopy

The skeletal muscle consists of three to four pure types of muscle cells (also called muscle fibers) identified as type I, type IIA, type IIX and/or type IIB in different proportions depending on the muscle function. They differ in their contraction speeds and metabolic pathways. Type I fibers are slow-twitch while type II fibers are fast twitch. The energy required to maintain cell homeostasis and muscle contraction is provided by the hydrolysis of ATP. The fibers IIX and IIB regenerate ATP by anaerobic glycolysis with lactate production. Fibers I and IIA favor cellular respiration (glycolysis + Krebs cycle). The latter are rich in mitochondria, where the cell respiration take place, and in myoglobin which carries oxygen to mitochondria. The intracellular composition of fibers therefore depends on their metabolic and contractile characteristics. The objective of our work was to study the impact of these slight differences in composition on the optical properties of muscle cells. Our hypothesis was, in part, based on the autofluorescence detection of NADH which is more concentrated in the mitochondria and thus in the oxidative metabolism fibers. Therefore, we studied the impact of cell type on the fluorescent response following excitation in deep UV. Rat soleus muscle consisting of I and IIA fibers and extensor digitorum longus (EDL) muscle consisting of I, IIA, IIX and IIB fibers were used as models. On each muscle, fibers, previously identified on their cell types by immunohistofluorescence, were analyzed by synchrotron fluorescence microspectroscopy on stain-free serial muscle cross sections. Muscle fibers excited at 275 nm showed differences in fluorescence emission intensity among fiber types at 302 (assigned to tyrosine fluorescence), 325, 346 (both assigned to tryptophan fluorescence) and 410 nm (assigned to NADH fluorescence). The 410/325 ratio decreased significantly with contractile and metabolic features in EDL muscle, ranked I>IIA>IIX>IIB fibers (p< 0.01). In a subsequent experiment, we acquired autofluorescence images for fast fiber types discrimination on label free histological sections. Computer processing of the images allowed us to improve the contrast and identify the metabolic types of fibers with a fairly good reliability. These studies highlight the usefulness of autofluorescence signals to characterize histological cross section of muscle fibers with no staining chemicals

Postmortem changes in muscle fibres autofluorescence

After slaughter, the muscle cells undergo biochemical and physicochemical changes which may affect their autofluorescence characteristics. The postmortem metabolism kinetic of rat EDL and soleus muscles was assessed by glycogen depletion determination while autofluorescent response of different muscle fiber types was investigated by Deep UV synchrotron microspectroscopy at slaughter and and 24 hours postmortem. Following a 275 nm excitation, emission fluorescence spectra showed discrimination depending on postmortem time (T0 versus T24h) on both muscles at 346 and 302 nm and to a lesser extent at 408 and 325 nm. Taken individually, all fiber types are discriminated but with variable accuracy, the type IIA showing better separation of T0 comparing to T24h than other fiber types. These results highlight the relevance of using the autofluorescent response of muscle cells to rapidly assess their state of postmortem changes

Postmortem change in muscle fibre autofluorescence

Merisiers, F-91120 Gif sur Yvette, France *[email protected] Abstract – After slaughter, the muscle cells undergo biochemical and physicochemical changes which may affect their autofluorescence characteristics. The postmortem metabolism kinetic of rat EDL and soleus muscles was assessed by glycogen depletion determination while autofluorescent response of different muscle fiber types was investigated by Deep UV synchrotron microspectroscopy at slaughter and and 24 hours postmortem. Following a 275 nm excitation, emission fluorescence spectra showed discrimination depending on postmortem time (T0 versus T24h) on both muscles at 346 and 302 nm and to a lesser extent at 408 and 325 nm. Taken individually, all fiber types are discriminated but with variable accuracy, the type IIA showing better separation of T0 comparing to T24h than other fiber types. These results highlight the relevance of using the autofluorescent response of muscle cells to rapidly assess their state of postmortem changes

Les bactéries lactiques sous la lumière du synchrotron pour comprendre les mécanismes de cryotolérance

Les bactéries lactiques sous la lumière du synchrotron pour comprendre les mécanismes de cryotolérance. Société Française de Microbiologi

Les bactéries lactiques sous la lumière du synchrotron pour comprendre les mécanismes de cryotolérance

Les bactéries lactiques sous la lumière du synchrotron pour comprendre les mécanismes de cryotolérance. Société Française de Microbiologi

Synchrotron UV−Visible Multispectral Luminescence Microimaging of Historical Samples

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