ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Modulation of CA1 dynamics by extrahippocampal inputs during development

L’activité spontanée façonne les réseaux neuronaux durant la période développementale. Dans la région de CA1, les différents motifs d’activité décrits in vitro renseignent sur le niveau de connectivité locale. Cependant, de plus en plus d’études soulignent le rôle des afférences externes sur le développement des circuits du néocortex, mais celui des afférences extra-hippocampiques sur le développement de la dynamique locale de CA1 reste peu renseigné. Des études récentes suggèrent toute fois que les activations du cortex entorhinal (EC) et de la ligne ventro-médiale du thalamus (VMT) sont corrélées avec les activités de réseau de la région de CA1 enregistrées in vivo. Dans le cadre de ma thèse, je me suis intéressé au lien de causalité entre les afférences extra-hippocampiques et la dynamique de CA1 pendant la première semaine post-natale, tout en révélant les circuits locaux impliqués. Pour cela, j’ai réalisé des injections stéréotaxiques de virus dans le VMT ou le EC de souris à la naissance, permettant ainsi de manipuler en opto- et chémo-génétique ces entrées extra-hippocampiques au cours d’enregistrements en imagerie calcique à 2 photons et électrophysiologiques. Les résultats montrent un rôle important des entrées du VMT et du EC sur la dynamique des réseaux neuronaux de CA1 en fin de première semaine post-natale. Ils montrent également l’intégration de ces afférences par le réseau de CA1, et mettent en évidence deux circuits locaux distincts où des neurones GABAergiques jouent un rôle prédominant. Cette thèse démontre un rôle essentiel des entrées extra-hippocampiques sur la maturation du réseau de CA1 au cours du développement.Spontaneous activity shapes neural networks during the developmental period. In the CA1 region, the different patterns of activity described in vitro provide information about the level of local connectivity. However, many studies point the role of external afferents on the development of neocortical circuits, but the role of extra-hippocampal inputs on the development of local dynamics in CA1 remains poorly understood. Recent studies suggest that activations of the entorhinal cortex (EC) and the ventral midline thalamus (VMT) are correlated with network activities in the CA1 region recorded in vivo. In my thesis, I investigated the causal link between extra-hippocampal afferents and CA1 dynamics during the first postnatal week, while revealing the involved local circuits. To do so, I performed stereotaxic injections of virus into the VMT or the EC of mice at birth, allowing opto- and chemo-genetic manipulation of these extra-hippocampal inputs during 2-photon calcium imaging and electrophysiological recordings. The results show an important role of the VMT and the EC inputs on the dynamics of CA1 neural networks at the end of the first postnatal week. They also show the integration of these afferents by the CA1 network and highlight two distinct local circuits where GABAergic neurons play a predominant role. This thesis demonstrates an essential role of extra-hippocampal inputs on the maturation of the CA1 network during development

Impact of Heart Transplantation on Survival in Patients on Venoarterial Extracorporeal Membrane Oxygenation at Listing in France

International audienceBackground Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a short-term circulatory support in patients with refractory cardiogenic shock providing a bridge to long-term mechanical circulatory support or transplantation. In France, a higher priority status is granted to transplant candidates on VA-ECMO than to those on long-term mechanical circulatory support. This study aimed to evaluate the impact of transplantation as primary therapy on survival in patients on VA-ECMO at listing. Methods This was a retrospective analysis of data from the French national registry CRISTAL including all patients (n = 866) newly registered on the waiting list for heart transplantation between January 2010 and December 2011. We compared outcomes of 80 patients on VA-ECMO at listing to outcomes of the comparison group. In the VA-ECMO group, a Cox proportional hazard model with transplantation as a time dependent variable was used to evaluate the effect of transplantation on survival. Results Patients on VA-ECMO were more often on ventilator and dialysis and had a higher bilirubin level than other candidates. One-year overall survival rate was lower in candidates from the study group (52.2%) compared with comparison group (75.5%), (P < 0.01). One-year posttransplant survival was 70% in the VA-ECMO group and 81% in comparison group (P = 0.06). In the VA-ECMO group, transplantation was associated with a lower risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.2-0.9). Conclusions Transplantation provides a survival benefit in listed patients on VA-ECMO even if posttransplant survival remains inferior than for patients without VA-ECMO. Transplantation may be considered to be an acceptable primary therapy in selected patients on VA-ECMO

Development of early-born γ-Aminobutyric acid hub neurons in mouse hippocampus from embryogenesis to adulthood

International audienceEarly-born g-aminobutyric acid (GABA) neurons (EBGNs) are major components of the hippocampal circuit because at early postnatal stages they form a subpopu-lation of " hub cells " transiently supporting CA3 network synchronization (Picardo et al. [2011] Neuron 71:695– 709). It is therefore essential to determine when these cells acquire the remarkable morphofunctional attributes supporting their network function and whether they develop into a specific subtype of interneuron into adulthood. Inducible genetic fate mapping conveniently allows for the labeling of EBGNs throughout their life. EBGNs were first analyzed during the perinatal week. We observed that EBGNs acquired mature characteristics at the time when the first synapse-driven synchronous activities appeared in the form of giant depolarizing potentials. The fate of EBGNs was next analyzed in the adult hippocampus by using anatomical characterization. Adult EBGNs included a significant proportion of cells projecting selectively to the septum; in turn, EBGNs were targeted by septal and entorhinal inputs. In addition, most EBGNs were strongly targeted by cholinergic and monoaminergic terminals, suggesting significant subcortical innervation. Finally, we found that some EBGNs located in the septum or the entorhi-nal cortex also displayed a long-range projection that we traced to the hippocampus. Therefore, this study shows that the maturation of the morphophysiological properties of EBGNs mirrors the evolution of early network dynamics, suggesting that both phenomena may be causally linked. We propose that a subpopulation of EBGNs forms into adulthood a scaffold of GABAergic projection neurons linking the hippocampus to distant structures

Characterization and Plasma Measurement of the WE-14 Peptide in Patients with Pheochromocytoma

International audienceGranins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors. The aim of the present study was to investigate the tumoral chromogranin A (CgA)-derived peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with pheochromocytoma, but returned to normal values after surgical resection of the tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of paragangliomas and sporadic or malignant pheochromocytomas if taken separately to account for the heterogeneity of the tumor. These data indicate that WE-14 is produced in pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell tumor. In addition, in association with other biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for pheochromocytoma. These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors

MK-MOBIBACK : un dispositif hybride et intégré pour enquêter finement les mobilités quotidiennes des familles

International audienc

MK-MOBIBACK : un dispositif hybride et intégré pour enquêter finement les mobilités quotidiennes des familles

International audienc

MK-MOBIBACK : un dispositif hybride et intégré pour enquêter finement les mobilités quotidiennes des familles

International audienc

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock

International audiencePURPOSE: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. METHODS: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted \textgreater6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. RESULTS: Sixty-five patients (47 %) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age \textgreater60, female sex, body mass index \textgreater25 kg/m(2), Glasgow coma score \textless6, creatinine \textgreater150 μmol/L, lactate (\textless2, 2-8, or \textgreater8 mmol/L), and prothrombin activity \textless50 %. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7 % for ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95 % CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34 % (95 % CI 20-49 %) anxiety, 20 % (95 % CI 8-32 %) depression, and 5 % (95 % CI 0-12 %) PTSD symptoms reported. CONCLUSIONS: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patient