Survival outcomes and mobilization during venovenous extracorporeal membrane oxygenation: a retrospective cohort study

IntroductionVenovenous extracorporeal membrane oxygenation (V-V ECMO) can be considered in critically ill patient in severe pulmonary failure. However, the mobilization of patients on V-V ECMO can be challenging due to logistic and safety concerns. This study aimed to investigate whether 30 days survival was improved in patients who were mobilized during V-V ECMO support.MethodsWe conducted a retrospective cohort all-comer study that included all patients cannulated for V-V ECMO at a single center. Patients with a V-V ECMO duration below 24 h were excluded from the analysis. The patients were grouped based on the ICU mobility scale documented during V-V ECMO support. The primary endpoint was 30 days survival, and secondary endpoints included weaning from ECMO and mechanical ventilation, as well as hospital survival.ResultsA total of 343 patients were included in the study, with a median age of 56 years and 32% were female. Among them, 28% had chronic lung disease. The ICU mobilization scale ≥2 during ECMO was documented in 62/343 (18%) patients. There were no significant differences in age, gender and preexisting lung disease. Duration of ICU stay (13.1 vs. 15.6 days), time on ECMO (186 vs. 190 h) and mechanical ventilation (11.2 vs. 13.6 days) were slightly shorter in patients with ICU mobility scale <2 compared to those with ≥2 (all p = 0.0001). However, patients with ICU mobilization scale ≥2 showed significantly better 30 days survival (71.0 vs. 48.0%, OR 2.6 (1.5 to 4.8), p = 0.0012) compared to those with <2. In the ≥2 mobility scale group, a significantly higher number of patients were successfully weaned from the ventilator (61.3 vs. 46.6%, OR 1.8 (1.0 to 3.2), p = 0.049). A stronger correlation was observed between more intense mobilizations, such as being in a standing position (OR 5.0 (1.7 to 14.0), p = 0.0038), and higher 30 days survival.ConclusionThe findings of this study suggest that active mobilization during V-V ECMO support is associated with improved 30 days survival and successful weaning from the respirator. Incorporating mobilization as part of the therapeutic approach during ECMO support may offer potential benefits for critically ill patients

Pumpless Extracorporeal Hemadsorption Technique (pEHAT) : A Proof-of-Concept Animal Study

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes

A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae

Activation (in the following referred to as firing) of replication origins is a continuous and irreversible process regulated by availability of DNA replication molecules and cyclin-dependent kinase activities, which are often altered in human cancers. The temporal, progressive origin firing throughout S phase appears as a characteristic replication profile, and computational models have been developed to describe this process. Although evidence from yeast to human indicates that a range of replication fork rates is observed experimentally in order to complete a timely S phase, those models incorporate velocities that are uniform across the genome. Taking advantage of the availability of replication profiles, chromosomal position and replication timing, here we investigated how fork rate may affect origin firing in budding yeast. Our analysis suggested that patterns of origin firing can be observed from a modulation of the fork rate that strongly correlates with origin density. Replication profiles of chromosomes with a low origin density were fitted with a variable fork rate, whereas for the ones with a high origin density a constant fork rate was appropriate. This indeed supports the previously reported correlation between inter-origin distance and fork rate changes. Intriguingly, the calculated correlation between fork rate and timing of origin firing allowed the estimation of firing efficiencies for the replication origins. This approach correctly retrieved origin efficiencies previously determined for chromosome VI and provided testable prediction for other chromosomal origins. Our results gain deeper insights into the temporal coordination of genome duplication, indicating that control of the replication fork rate is required for the timely origin firing during S phase

A variable fork rate affects timing of origin firing and S phase dynamics in Saccharomyces cerevisiae

Activation (in the following referred to as firing) of replication origins is a continuous and irreversible process regulated by availability of DNA replication molecules and cyclin-dependent kinase activities, which are often altered in human cancers. The temporal, progressive origin firing throughout S phase appears as a characteristic replication profile, and computational models have been developed to describe this process. Although evidence from yeast to human indicates that a range of replication fork rates is observed experimentally in order to complete a timely S phase, those models incorporate velocities that are uniform across the genome. Taking advantage of the availability of replication profiles, chromosomal position and replication timing, here we investigated how fork rate may affect origin firing in budding yeast. Our analysis suggested that patterns of origin firing can be observed from a modulation of the fork rate that strongly correlates with origin density. Replication profiles of chromosomes with a low origin density were fitted with a variable fork rate, whereas for the ones with a high origin density a constant fork rate was appropriate. This indeed supports the previously reported correlation between inter-origin distance and fork rate changes. Intriguingly, the calculated correlation between fork rate and timing of origin firing allowed the estimation of firing efficiencies for the replication origins. This approach correctly retrieved origin efficiencies previously determined for chromosome VI and provided testable prediction for other chromosomal origins. Our results gain deeper insights into the temporal coordination of genome duplication, indicating that control of the replication fork rate is required for the timely origin firing during S phase