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Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

Acute pulmonary oedema (APE) is one of the most common causes of unscheduled hospital admissions among patients 65 years old or older [1, 2], with up to half being critically ill [2]. APE is associated with a high mortality and rate of re-hospitalisation. Whilst in-hospital mortality ranges from 4 to 10%, the readmission rate for APE increases with time after discharge, ranging from 15% at 1 month to 45–50% at 6 months. One in three APE patients dies within 1 year [1, 2]. In this document we outline 10 key questions ICU specialists should address when managing APE.

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.

A new and suitable multicomponent one-pot reaction was developed for the synthesis of 2-amino-3-cyanopyridine derivatives. Background: This synthesis was demonstrated by the efficient and easy access to a variety of substituted 2-aminopyridines using enaminones as key precursors under solvent-free conditions. Methods: A range of spectroscopic techniques was used to determine and confirm the chemical structures (FTIR, 1H NMR, 13C NMR). The antimicrobial potency of synthesized compounds (2a–d) was tested using disk diffusion assays, and the Minimum Inhibitory Concentration (MIC) for the active compounds was determined against a panel of microorganisms, including Gram-positive and Gram-negative bacteria and yeasts. Moreover, a docking analysis was conducted by Molecular Operating Environment (MOE) software to provide supplementary information about the potential, as well as an ADME-T prediction to describe the pharmacokinetic properties of the best compound and its toxicity. Results: The results of the antimicrobial activity indicated that compound 2c showed the highest activity against Gram-positive bacteria, particularly S. aureus and B. subtilis whose MIC values were 0.039 ± 0.000 µg·mL−1. The results of the theoretical study of compound 2c were in line with the experimental data and exhibited excellent antibacterial potential. Conclusions: On the basis of the obtained results, compound 2c can be used as an antibacterial agent model with high antibacterial potency.

A convenient and effective synthesis of imidazo[1,2-a]pyrimidine derivatives has been developed under microwave irradiations using Al2O3 as a catalyst in solvent-free conditions. The functionalized imidazo[1,2-a]pyrimidine derivatives are useful in biochemistry and medical science. In our investigation, the antimicrobial activity of the synthesized compounds was evaluated against 13 microorganisms, including 6 Gram-positive bacteria, 4 Gram-negative bacteria, and 3 pathogenic fungi. Bioactivity tests revealed that the majority of the compounds exhibited good antimicrobial activity. Finally, molecular docking simulations and ADME-T predictions were performed, showing that the most active compounds have good binding modes with microbial targets and promising pharmacokinetic safety profiles.

Background Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. Methods In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. Results The mean Crs in 372 patients was 37.6 ± 13 mL/cmH 2 O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO 2 /FiO 2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98–1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13–3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88–0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH 2 O vs 37.8 ± 11.4 mL/cmH 2 O, p  < 0.001). The decrease in Crs was not associated with day-28 outcome. Conclusion In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH 2 O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.