Collective Epithelial Migration Drives Kidney Repair after Acute Injury

Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney’s remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI

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/)

[Monnaie : Billon, Incertain, Égypte, Vabalathe]

Ancien possesseur : Delepierre, Jean (1889-1963). Ancien possesseurAncien possesseur : Delepierre, Marie (1896-1974). Ancien possesseurAppartient à l’ensemble documentaire : MonnGr

[Monnaie : Bronze, Alexandrie, Égypte, Vabalathe]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Bronze, Alexandrie, Égypte, Vabalathe]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Bronze, Alexandrie, Égypte, Vabalathe]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Tétradrachme, Billon, Vabalathe, Égypte, Alexandrie]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Bronze, Alexandrie, Égypte, Vabalathe]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Tétradrachme, Billon, Vabalathe, Égypte, Alexandrie]

Appartient à l’ensemble documentaire : MonnGr

[Monnaie : Tétradrachme, Billon, Vabalathe, Égypte, Alexandrie]

Appartient à l’ensemble documentaire : MonnGr