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Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital- acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation-inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributed to early antibacterial defense against P. aeruginosa. Consequently, P. aeruginosa-binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substitute. Our study provides a mechanistic explanation for the welldocumented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy., Introduction National and international point-prevalence studies show that 64%-71% of all patients in intensive care units (ICUs) receive antibiotics (1, 2) and up to 10%-51% suffer from hospital-acquired infections (HAIs) [...]

Purpose Pump-driven veno-venous extracorporeal CO.sub.2-removal (ECCO.sub.2-R) increasingly takes root in hypercapnic lung failure to minimize ventilation invasiveness or to avoid intubation. A recently developed device (iLA activve.sup.®, Novalung, Germany) allows effective decarboxylation via a 22 French double lumen cannula. To assess determinants of gas exchange, we prospectively evaluated the performance of ECCO.sub.2-R in ten patients receiving iLA activve.sup.® due to hypercapnic respiratory failure. Methods Sweep gas flow was increased in steps from 1 to 14 L/min at constant blood flow (phase 1). Similarly, blood flow was gradually increased at constant sweep gas flow (phase 2). At each step gas transfer via the membrane as well as arterial blood gas samples were analyzed. Results During phase 1, we observed a significant increase in CO.sub.2 transfer together with a decrease in PaCO.sub.2 levels from a median of 66 mmHg (range 46-85) to 49 (31-65) mmHg from 1 to 14 L/min sweep gas flow (p < 0.0001), while arterial oxygenation deteriorated with high sweep gas flow rates. During phase 2, oxygen transfer significantly increased leading to an increase in PaO.sub.2 from 67 (49-87) at 0.5 L/min to 117 (66-305) mmHg at 2.0 L/min (p < 0.0001). Higher blood flows also significantly enhanced decarboxylation (p < 0.0001). Conclusions Increasing sweep gas flow results in effective CO.sub.2-removal, which can be further reinforced by raising blood flow. The clinically relevant oxygenation effect in this setting could broaden the range of indications of the system and help to set up an individually tailored configuration., Author(s): Alexander Hermann [sup.1], Katharina Riss [sup.1], Peter Schellongowski [sup.1], Andja Bojic [sup.1], Philipp Wohlfarth [sup.1], Oliver Robak [sup.1], Wolfgang R. Sperr [sup.1], Thomas Staudinger [sup.1] Author Affiliations: (1) grid.22937.3d, [...]

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373). [ABSTRACT FROM AUTHOR]

Abstract Background Cardiopulmonary resuscitation (CPR) training is gaining more importance for medical students. There were many attempts to improve the basic life support (BLS) skills in medical students, some being rather successful, some less. We developed a new problem based learning curriculum, where students had to teach CPR to cardiac arrest survivors in order to improve the knowledge about life support skills of trainers and trainees. Methods Medical students who enrolled in our curriculum had to pass a 2 semester problem based learning session about the principles of cardiac arrest, CPR, BLS and defibrillation (CPR-D). Then the students taught cardiac arrest survivors who were randomly chosen out of a cardiac arrest database of our emergency department. Both, the student and the Sudden Cardiac Death (SCD) survivor were asked about their skills and knowledge via questionnaires immediately after the course. The questionnaires were then used to evaluate if this new teaching strategy is useful for learning CPR via a problem-based-learning course. The survey was grouped into three categories, namely "Use of AED", "CPR-D" and "Training". In addition, there was space for free answers where the participants could state their opinion in their own words, which provided some useful hints for upcoming programs. Results This new learning-by-teaching strategy was highly accepted by all participants, the students and the SCD survivors. Most SCD survivors would use their skills in case one of their relatives goes into cardiac arrest (96%). Furthermore, 86% of the trainees were able to deal with failures and/or disturbances by themselves. On the trainer's side, 96% of the students felt to be well prepared for the course and were considered to be competent by 96% of their trainees. Conclusion We could prove that learning by teaching CPR is possible and is highly accepted by the students. By offering a compelling appreciation of what CPR can achieve in using survivors from SCD as trainees made them go deeper into the subject of resuscitation, what also might result in a longer lasting benefit than regular lecture courses in CPR.