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/)

Hereditary stomatocytosis: advances in knowledge of forms with dehydrated red blood cells

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Comparison between a Camera and a Four Quadrant Detector, in the Measurement of Red Blood Cell Deformability as a Function of Osmolality

4 pagesInternational audienceThe ability of red blood cells (RBC) to deform under vascular conditions is essential for circulation. RBC deformability, measured at different shear rates and osmolalities, provides a useful way to evaluate RBC function and is used to diagnose several hereditary blood disorders. In clinical practice, ektacytometry has been used as a routine automated technique for measuring RBC deformability under shear stress at known osmolalities. RBC suspension is exposed to laser light and the resulting diffraction pattern is recorded. The mean deformability of the cells is characterized by the diffraction pattern. Our study is the first to compare the correspondence between two methods that measure diffraction simultaneously, on the same apparatus. Additionally, while others conducted studies under varying shear we used varying osmolalities. A laser beam splitter produced two identical diffraction patterns, evaluated by synchronous data acquisition and analysis: One pattern was acquired by a digital camera and analyzed by image processing software. The other was analyzed using photodiode measurement at four fixed points and a microcontroller interface. Data analysis resulted in two deformability vs. osmolality curves. Comparing these curves shows excellent overlap in shape with a clear difference in amplitude. Since routine Manuscript received Jan 15, 2013; revised March 1, 2013. patient curves are always compared to a normal control curve, the amplitue difference is not significant. Our results indicate that either method may be used for clinically-usable interpretation of RBC deformability, but also that additional studies are required in order to compare repeatability for both methods, and to demonstrate that the two curves overlap for a variety of pathologies

Comparison between a Camera and a Four Quadrant Detector, in the Measurement of Red Blood Cell Deformability as a Function of Osmolality

4 pagesInternational audienceThe ability of red blood cells (RBC) to deform under vascular conditions is essential for circulation. RBC deformability, measured at different shear rates and osmolalities, provides a useful way to evaluate RBC function and is used to diagnose several hereditary blood disorders. In clinical practice, ektacytometry has been used as a routine automated technique for measuring RBC deformability under shear stress at known osmolalities. RBC suspension is exposed to laser light and the resulting diffraction pattern is recorded. The mean deformability of the cells is characterized by the diffraction pattern. Our study is the first to compare the correspondence between two methods that measure diffraction simultaneously, on the same apparatus. Additionally, while others conducted studies under varying shear we used varying osmolalities. A laser beam splitter produced two identical diffraction patterns, evaluated by synchronous data acquisition and analysis: One pattern was acquired by a digital camera and analyzed by image processing software. The other was analyzed using photodiode measurement at four fixed points and a microcontroller interface. Data analysis resulted in two deformability vs. osmolality curves. Comparing these curves shows excellent overlap in shape with a clear difference in amplitude. Since routine Manuscript received Jan 15, 2013; revised March 1, 2013. patient curves are always compared to a normal control curve, the amplitue difference is not significant. Our results indicate that either method may be used for clinically-usable interpretation of RBC deformability, but also that additional studies are required in order to compare repeatability for both methods, and to demonstrate that the two curves overlap for a variety of pathologies

Carbon monoxide rebreathing method is a reliable test to evaluate the red cell mass in polycythaemia

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Artificial intelligence to empower diagnosis of myelodysplastic syndromes by multiparametric flow cytometry

International audienceThe diagnosis of myelodysplastic syndromes (MDS) might be challenging and relies on the convergence of cytological, cytogenetic, and molecular arguments. Multiparametric flow cytometry (MFC) helps diagnose MDS, especially when other features are non-contributory, but remains underestimated mostly due to a lack of standardization of cytometers. We present here an innovative model integrating artificial intelligence (AI) with MFC to improve the diagnosis and the classification of MDS. We develop a machine learning model by elasticnet algorithm trained on a cohort of 191 patients and only based on flow cytometry parameters selected by Boruta algorithm, to build a simple but reliable prediction score with 5 parameters. Our MDS prediction score assisted by AI greatly improves the sensitivity of Ogata score while keeping an excellent specificity validated on an external cohort of 89 patients with an AUC = 0.935. This model allows the diagnosis of both high and low risk MDS with 91.8% sensitivity and 92.5% specificity. Interestingly, it highlights a progressive evolution of the score from clonal hematopoiesis of indeterminate potential (CHIP) to highrisk MDS, suggesting a linear evolution between these different stages. By significantly decreasing the overall misclassification of 52% for patients with MDS and of 31.3% for those without MDS (p=0.02), our AI-assisted prediction score outperforms the Ogata score and positions itself as a reliable tool to help diagnose myelodysplastic syndromes

Red blood cell Gardos channel (KCNN4): the essential determinant of erythrocyte dehydration in hereditary xerocytosis

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Hereditary Xerocytosis: Differential Behavior of PIEZO1 Mutations in the N-Terminal Extracellular Domain Between Red Blood Cells and HEK Cells

International audienceHereditary Xerocytosis, a rare hemolytic anemia, is due to gain of function mutations in PIEZO1, a non-selective cation channel activated by mechanical stress. How these PIEZO1 mutations impair channel function and alter red blood cell (RBC) physiology, is not completely understood. Here, we report the characterization of mutations in the N-terminal part of the protein (V598M, F681S and the double mutation G782S/R808Q), a part of the channel that was subject of many investigations to decipher its role in channel gating. Our data show that the electrophysiological features of these PIEZO1 mutants expressed in HEK293T cells are different from previously characterized PIEZO1 mutations that are located in the pore or at the C-terminal extracellular domain of the protein. Although RBC with PIEZO1 mutations showed a dehydrated phenotype, the activity of V598M, F681S or R808Q in response to stretch was not significantly different from the WT channels. In contrast, the G782S mutant showed larger currents compared to the WT PIEZO1. Interestingly, basal activity of all the mutated channels was not significantly altered at the opposite of what was expected according to the decreased water and cation contents of resting RBC. In addition, the features of mutant PIEZO1 expressed in HEK293 cells do not always correlate with the observation in RBC where PIEZO1 mutations induced a cation leak associated with an increased conductance. Our work emphasizes the role of the membrane environment in PIEZO1 activity and the need to characterize RBC permeability to assess pathogenicity to PIEZO1 mutants associated with erythrocyte diseases