Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl4, 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged. We then measured portal pressure, intrahepatic vascular resistance, liver fibrosis and bacterial translocation. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl4 (15.2±0.5 vs. 11.8±0.4mmHg; p=0.001) rats. In PPVL animals, we observed less bacterial translocation (-36%; p=0.041), a decrease in lipopolysaccharide binding protein (-30%; p=0.024) and splanchnic tumour necrosis factor α levels (-39%; p=0.044) after PX treatment. In CCl4 rats, PX decreased fibrotic Sirius Red area (-43%; p=0.005), hepatic hydroxyproline (-66%; p<0.001), and expression of profibrogenic proteins (Col1a1, α smooth muscle actin, transforming growth factor β). CCl4-PX rats had significantly lower transaminase levels and reduced hepatic macrophage infiltration. Moreover, PX induced sinusoidal vasodilation (upregulation of cystathionase, dimethylaminohydrolase (DDAH)1, endothelial nitric oxide synthase (eNOS), GTP-cyclohydrolase1) and reduced intrahepatic vasoconstriction (downregulation of endothelin-1, p-Moesin). In cirrhosis, PX improved endothelial dysfunction (decreased von-Willebrand factor) and normalized overexpression of vascular endothelial growth factor, platelet-derived growth factor and angiopoietins. While short-term 3-day PX treatment reduced portal pressure (-14%; p=0.041) by restoring endothelial function, 14week PX therapy additionally inhibited sinusoidal remodelling and decreased portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut.

Background: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). Objective: Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. Methods: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. Results: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). Conclusions: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.

Background Visual attention (VA) is important for situation awareness and decision-making. Eye tracking can be used to analyse the VA of healthcare providers. No study has examined eye tracking during neonatal resuscitation. Objective To test the use of eye tracking to examine VA during neonatal resuscitation. Methods Six video recordings were obtained using eye tracking glasses worn by resuscitators during the first 5 min of neonatal resuscitation. Videos were analysed to obtain (i) areas of interest (AOIs), (ii) time spent on each AOI and (iii) frequency of saccades between AOIs. Results Five videos were of acceptable quality and analysed. Only 35% of VA was directed at the infant, with 33% at patient monitors and gauges. There were frequent saccades (0.45/s) and most involved patient monitors. Conclusion During neonatal resuscitation, VA is often directed away from the infant towards patient monitors. Eye tracking can be used to analyse human performance during neonatal resuscitation.

OBJECTIVES: Our aim for this study was to test whether visual and verbal feedback compared with instructor-led feedback improve the quality of pediatric cardiopulmonary resuscitation (CPR). METHODS: There were 653 third-year medical students randomly assigned to practice pediatric CPR on 1 of 2 manikins (infant and adolescent; n = 344 and n = 309, respectively). They were further randomly assigned to 1 of 3 feedback groups: The instructor feedback (IF) group (n = 225) received traditional, instructor-led feedback without any additional feedback device. The device feedback (DF) group (n = 223) received real-time visual feedback from a feedback device. The instructor and device feedback (IDF) group (n = 205) received verbal feedback from an instructor who continuously reviewed the trainees’ performance using the feedback device. After the training, participants’ CPR performance was assessed on the same manikin while no feedback was being provided. RESULTS: For the primary outcome of total compression score, participants in the DF and IDF groups performed similarly, with both groups showing scores significantly (P < .001) better than those of the IF group. The same findings held for correct hand position and the proportion of complete release. For compression rate, the DF group was at the higher end of the guideline for 100 to 120 chest compressions per minute compared with the IF and IDF groups (both P < .001). No effect of feedback on compression depth was found. CONCLUSIONS: Chest compression performance significantly improved with both visual and verbal feedback compared with instructor-led feedback. Feedback devices should be implemented during pediatric resuscitation training to improve resuscitation performance.

Background: The aim of this study was to investigate the effect of feedback devices on visual attention and the quality of pediatric resuscitation. Methods: This was a randomized cross-over simulation study at the Medical University of Vienna. Participants were students and neonatal providers performing four resuscitation scenarios with the support of feedback devices randomized. The primary outcome was the quality of resuscitation. Secondary outcomes were total dwell time (=total duration of visit time) on areas of interest and the workload of participants. Results: Forty participants were analyzed. Overall, chest compression (P < 0.001) and ventilation quality were significantly better (P = 0.002) when using a feedback device. Dwell time on the feedback device was 40.1% in the ventilation feedback condition and 48.7% in the chest compression feedback condition. In both conditions, participants significantly reduced attention from the infant’s chest and mask (72.9 vs. 32.6% and 21.9 vs. 12.7%). Participants’ subjective workload increased by 3.5% (P = 0.018) and 8% (P < 0.001) when provided with feedback during a 3-min chest compression and ventilation scenario, respectively. Conclusions: The quality of pediatric resuscitation significantly improved when using real-time feedback. However, attention shifted from the manikin and other equipment to the feedback device and subjective workload increased, respectively. Impact: Cardiopulmonary resuscitation with feedback devices results in a higher quality of resuscitation and has the potential to lead to a better outcome for patients. Feedback devices consume attention from resuscitation providers. Feedback devices were associated with a shift of visual attention to the feedback devices and an increased workload of participants. Increased workload for providers and benefits for resuscitation quality need to be balanced for the best effect.

Background: High-quality chest compression is essential during neonatal cardiopulmonary resuscitation (CPR). However, the optimal compression to ventilation ratio (C:V) that should be used during neonatal CPR to optimize coronary and cerebral perfusion while providing adequate ventilation remains unknown. Objective: We hypothesized that different C:V ratios (e.g., 2: 1 or 4: 1) will reduce the time to return of spontaneous circulation (ROSC) in severely asphyxiated piglets. Methods: Thirty-one newborn piglets (1–4 days old) were anesthetized, intubated, instrumented, and exposed to 50-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into 4 groups: 2: 1 (n = 8), 3: 1 (n = 8), 4: 1 (n = 8) C:V ratio, or a sham group (n = 7). Cardiac function, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Results: Thirty-one piglets were included in the study, and there was no difference in the duration of asphyxia or the degree of asphyxiation (as indicated by pH, PaCO₂, and lactate) among the different groups. The median (IQR) time to ROSC was similar between the groups with 127 (82–210), 96 (88–126), and 119 (83–256) s in the 2: 1, 3: 1, and 4: 1 C:V ratio groups, respectively (p = 0.67 between groups). Similarly, there was no difference in 100% oxygen requirement or epinephrine administration between the experimental groups. Conclusions: Different C:V ratios resulted in similar ROSC, mortality, oxygen, and epinephrine administration during resuscitation in a porcine model of neonatal asphyxia.