Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Response of cells and tissues to shear stress

Shear stress is essential for normal physiology and malignancy. Common physiological processes - such as blood flow, particle flow in the gut, or contact between migratory cell clusters and their substrate - produce shear stress that can have an impact on the behavior of different tissues. In addition, shear stress has roles in processes of biomedical interest, such as wound healing, cancer and fibrosis induced by soft implants. Thus, understanding how cells react and adapt to shear stress is important. In this Review, we discuss in vivo and in vitro data obtained from vascular and epithelial models; highlight the insights these have afforded regarding the general mechanisms through which cells sense, transduce and respond to shear stress at the cellular levels; and outline how the changes cells experience in response to shear stress impact tissue organization. Finally, we discuss the role of shear stress in collective cell migration, which is only starting to be appreciated. We review our current understanding of the effects of shear stress in the context of embryo development, cancer and fibrosis, and invite the scientific community to further investigate the role of shear stress in these scenarios

Dust arriving in the Amazon basin over the past 7,500 years came from diverse sources

International audienceA large amount of dust from the Sahara reaches the Amazon Basin, as observed with satellite imagery. This dust is thought to carry micronutrients that could help fertilize the rainforest. However, considering different atmospheric transport conditions, different aridity levels in South America and Africa and active volcanism, it is not clear if the same pathways for dust have occurred throughout the Holocene. Here we present analyses of Sr-Nd isotopic ratios of a lacustrine sediment core from remote Lake Pata in the Amazon region that encompasses the past 7,500 years before present, and compare these ratios to dust signatures from a variety of sources. We find that dust reaching the western Amazon region during the study period had diverse origins, including the Andean region and northern and southern Africa. We suggest that the Sahara Desert was not the dominant source of dust throughout the vast Amazon basin over the past 7,500 years