Early respiratory system reactance predicts respiratory outcomes in preterm infants: a retrospective, multicentre study.

OBJECTIVE: This multicenter, international, retrospective study aims to investigate whether respiratory system reactance (Xrs) assessed by respiratory oscillometry on the 7th day of life is associated with respiratory outcomes in preterm infants below 32 weeks' gestation. METHODS: Sinusoidal pressure oscillations (2-5 cmH2O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure (PEEP). We assessed the association of Xrs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD, according to Jensen et al. 2019) using logistic regression. We used the likelihood ratio test to evaluate whether Xrs z-score adds significantly to clinical predictors, including gestational age (GA), birth weight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model. RESULTS: One hundred and thirty-seven infants (median (Q1, Q3) GA=28.43 (26.11, 30.29) weeks) were included; 44 (32%) developed BPD. Xrs z-score was significantly associated with the duration of respiratory support (R2=0.35). Xrs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in Xrs, the OR for BPD increased by 60% and the respiratory support by eight days. In multivariable analysis, Xrs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively). CONCLUSION: Xrs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.

Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants.

RATIONALE: Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. OBJECTIVES: In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. METHODS: In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). RESULTS: We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1-23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants. CONCLUSIONS: The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

Positive end-expiratory pressure and surfactant administration mode influence function in ex-vivo premature sheep lungs.

AIM: Respiratory distress syndrome often necessitates endotracheal surfactant administration in extremely preterm infants. Our study aimed to explore a multi-modal simulation tool for investigating treatment strategies in ex vivo sheep lungs during spontaneous breathing. METHODS: An electromechanical lung simulator (xPULM) mimicking spontaneous breathing was coupled with a non-aerated premature sheep lung, replicating a premature respiratory system. Changes in tidal volume for different positive end-expiratory pressure (PEEP) levels prior to and after either bolus or nebulised surfactant administration were compared. RESULTS: In two preterm sheep lungs, we observed a progressive decline in tidal volume with increasing PEEP levels prior to surfactant delivery from 0.30 ± 0.01 mL at zero PEEP to 0.04 ± 0.01 mL at 15 cmH2O PEEP. Our measurements showed that both bolus (p < 0.05) and nebulised (p < 0.05) surfactant administration resulted in a significant increase in tidal volume, with no significant difference (p = 0.71) between the two methods. CONCLUSION: The experimental setup demonstrated the feasibility of xPULM for investigating the effectiveness of different PEEP levels and modes of surfactant administration with respect to tidal volume in premature sheep lungs. The lack of adequate lung water resorption in our model warrants further investigations.

Development of a 3D printed patient-specific neonatal brain simulation model using multimodality imaging for perioperative management.

BACKGROUND: Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system. METHODS: Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities. RESULTS: A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable. CONCLUSIONS: We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined. IMPACT: We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.

Regular lung recruitment maneuvers during high-frequency oscillatory ventilation in extremely preterm infants: a randomized controlled trial.

BACKGROUND: Lung recruitment maneuvers (LRMs) improve lung volume at initiation of high-frequency oscillatory ventilation (HFOV), but it is unclear when to repeat LRMs. We evaluated the efficiency of scheduled LRMs. METHODS: In a randomized controlled trial, extremely preterm infants on HFOV received either LRMs at 12-hour intervals and when clinically indicated (intervention) or only when clinically indicated (control). The primary outcome was the cumulative oxygen saturation index (OSI) over HFOV time, limited to 7 days. Additionally, LRMs were analyzed with respect to OSI improvement. RESULTS: Fifteen infants were included in each group. The mean (SD) postmenstrual age and weight at HFOV start were 23 + 6 (0 + 5) weeks and 650 (115) g in the intervention group and 24 + 4 (0 + 6) weeks (p = 0.03) and 615 (95) g (p = 0.38) in the control group. The mean (SD) cumulative OSI amounted to 4.95 (1.72) in the intervention versus 5.30 (2.08) in the control group (p = 0.61). The mean (SD) number of LRMs in 12 h was 1.3 (0.2) in the intervention versus 1.1 (0.5) in the control group (p = 0.13). Performing LRM when FiO2 > 0.6 resulted in a mean OSI reduction of 3.6. CONCLUSION: Regular versus clinically indicated LRMs were performed with equal frequency in preterm infants during HFOV, and consequently, no difference in lung volume was observed. LRMs seem to be most efficient at high FiO2. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04289324 (28/02/2020).

Comparing ventilation modes by electrical impedance segmentography in ventilated children.

Electrical impedance segmentography offers a new radiation-free possibility of continuous bedside ventilation monitoring. The aim of this study was to evaluate the efficacy and reproducibility of this bedside tool by comparing synchronized intermittent mandatory ventilation (SIMV) with neurally adjusted ventilatory assist (NAVA) in critically-ill children. In this prospective randomized case-control crossover trial in a pediatric intensive care unit of a tertiary center, including eight mechanically-ventilated children, four sequences of two different ventilation modes were consecutively applied. All children were randomized into two groups; starting on NAVA or SIMV. During ventilation, electric impedance segmentography measurements were recorded. The relative difference of vertical impedance between both ventilatory modes was measured (median 0.52, IQR 0-0.87). These differences in left apical lung segments were present during the first (median 0.58, IQR 0-0.89, p = 0.04) and second crossover (median 0.50, IQR 0-0.88, p = 0.05) as well as across total impedance (0.52 IQR 0-0.87; p = 0.002). During NAVA children showed a shift of impedance towards caudal lung segments, compared to SIMV. Electrical impedance segmentography enables dynamic monitoring of transthoracic impedance. The immediate benefit of personalized ventilatory strategies can be seen when using this simple-to-apply bedside tool for measuring lung impedance.

Long-term impact of systematic pain and sedation management on cognitive, motor, and behavioral outcomes of extremely preterm infants at preschool age.

BACKGROUND: Providing optimal pain relief is a challenging task when caring for premature infants. The aim of this study was to compare the long-term cognitive, motor, and behavioral outcomes of preterm infants before and after the implementation of a pain and sedation protocol. In addition, we investigated whether the increased opiate administration resulting after the implementation process had an impact on these outcomes. METHODS: Cognitive outcomes were evaluated using the Kaufman Assessment Battery for Children (KABC), neuromotor examinations were based on Amiel-Tison, and behavioral outcomes were assessed using the parent-reported Child Behavior Checklist (CBCL). RESULTS: One hundred extremely preterm infants were included in the study (control group, n = 53; intervention group, n = 47). No significant differences were found in cognitive and motor outcomes at preschool age. However, every increase in the cumulative opiate exposure for each 100 mg/kg was weakly significantly associated with a higher risk for autism spectrum features (adjusted odds ratio (aOR) = 1.822, 95% confidence interval (CI) [1.231-2.697]; P = 0.03) and withdrawn behavior (aOR = 1.822, 95% CI [1.231-2.697]; P = 0.03) at preschool age. CONCLUSION: Increased neonatal cumulative opiate exposure did not alter cognitive and motor outcomes but may represent a risk factor for autism spectrum and withdrawn behavior at preschool age. IMPACT: The implementation of a protocol for the management of pain and sedation in preterm infants resulted in increased cumulative opiate exposure. Our study adds further evidence that increased neonatal opiate exposure did  not alter cognitive and motor outcomes but may yield a potential risk factor for autism spectrum disorders and withdrawn behavior at preschool age. A vigilant use of opiates is recommended. Further studies are needed looking for novel pain management strategies and drugs providing optimal pain relief with minimal neurotoxicity.

Prediction of Nociception in Children Using the Nociceptive Flexion Reflex Threshold and the Bispectral Index-A Prospective Exploratory Observational Study.

OBJECTIVES: The prediction of patient responses to potentially painful stimuli remains a challenge in PICUs. We investigated the ability of the paintracker analgesia monitor (Dolosys GmbH, Berlin, Germany) measuring the nociceptive flexion reflex threshold, the cerebral sedation monitor bispectral index (Medtronic, Dublin, Ireland), the COMFORT Behavior, and the modified Face, Legs, Activity, Cry, Consolability Scale scores to predict patient responses following a noxious stimulus. DESIGN: Single-center prospective exploratory observational study. SETTING: Fourteen-bed multidisciplinary PICU at the University Children's Hospital, University Medical Center Hamburg Eppendorf, Germany. PATIENTS: Children on mechanical ventilation receiving analgesic and sedative medications. INTERVENTIONS: Noxious stimulation by way of endotracheal suctioning. MEASUREMENTS AND MAIN RESULTS: Two independent observers assessed modified Face, Legs, Activity, Cry, Consolability and COMFORT Behavior Scales scores during noxious stimulation (n = 59) in 26 patients. Vital signs were recorded immediately before and during noxious stimulation; bispectral index and nociceptive flexion reflex threshold were recorded continuously. Mean prestimulation bispectral index (55.5; CI, 44.2-66.9 vs 39.9; CI, 33.1-46.8; p = 0.007), and COMFORT Behavior values (9.5; CI, 9.2-13.2 vs 7.5; CI, 6.7-8.5; p = 0.023) were significantly higher in observations with a response than in those without a response. Prediction probability (Pk) values for patient responses were high when the bispectral index was used (Pk = 0.85) but only fair when the nociceptive flexion reflex threshold (Pk = 0.69) or COMFORT Behavior Scale score (Pk = 0.73) was used. A logistic mixed-effects model confirmed the bispectral index as a significant potential predictor of patient response (p = 0.007). CONCLUSIONS: In our sample of ventilated children in the PICU, bispectral index and nociceptive flexion reflex threshold provided good and fair prediction accuracy for patient responses to endotracheal suctioning.

Mirrored Ribs: A Sign for Pneumothorax in Neonates.

OBJECTIVES: To evaluate if "mirrored ribs"-a mirroring of chest structures-is a sign for pneumothorax in lung ultrasound in neonates. DESIGN: Retrospective study. SETTING: Medical University Vienna/General Hospital, Vienna, Austria. PATIENTS: All neonates admitted with clinical signs of pneumothorax between July 2018 and February 2019. INTERVENTIONS: Chest radiograph and lung ultrasound in succession. MEASUREMENTS AND MAIN RESULTS: Anterior-posterior chest radiograph and lung ultrasound were compared. "Mirrored ribs" were defined as mirroring of at least one rib and intercostal muscles in B-mode in the absence of B-lines. Twenty-nine cases in 26 patients were considered. Pneumothorax was diagnosed in 55% of cases using reported signs for pneumothorax in lung ultrasound and in 31% using chest radiograph. Lung ultrasound identified all pneumothoraces visible in chest radiograph. "Mirrored ribs" were visible in all patients with signs for pneumothorax and in none without signs for pneumothorax in lung ultrasound, representing a specificity and sensitivity of 100% compared with reported signs for pneumothorax in lung ultrasound. CONCLUSIONS: The occurrence of "mirrored ribs" in lung ultrasound in combination with absence of lung sliding, absence of B-lines and lung point might facilitate the rapid recognition of pneumothorax in neonates.

Left ventricular pumping during the transition-adaptation sequence in preterm infants: impact of the patent ductus arteriosus.

BackgroundPostnatally, the immature left ventricle (LV) is subjected to high systemic afterload. Hypothesizing that LV pumping would change during transition-adaptation, we analyzed the LV in preterm infants (GA≤32+6), clinically stable or with a hemodynamically significant patent ductus arteriosus (hPDA) by applying a pump model.MethodsPumping was characterized by EA (effective arterial elastance, reflecting afterload), EES (end-systolic LV elastance, reflecting contractility), EA/EES coupling ratios, descriptive EA:EES relations, and EA/EES graphs. Data calculated from echocardiography and blood pressure were analyzed by diagnosis (S group: clinically stable, no hPDA, n=122; hPDA group, n=53) and by periods (early transition: days of life 1-3; late transition: 4-7; and adaptation: 8-30).ResultsS group: LV pumping was characterized by an increased EA/EES coupling ratio of 0.65 secondary to low EES in early transition, a tandem rise of both EA and EES in late transition, and an EA/EES coupling ratio of 0.45 secondary to high EES in adaptation; hPDA group: time-trend analyses showed significantly lower EA (P<0.0001) and EES (P=0.006). Therefore, LV pumping was characterized by a lower EA/EES coupling ratio (P=0.088) throughout transition-adaptation.ConclusionsIn stable infants, facing high afterload, the immature LV, enhanced by the physiological PDA, increases its contractility. In hPDA, facing low afterload, the overloaded immature LV exhibits a consistently lower contractility.

The impact of extrauterine life on visual maturation in extremely preterm born infants.

BACKGROUND: Extrauterine life is an important factor when considering brain maturation. Few studies have investigated the development of visual evoked potentials (VEP) in extremely preterm infants, and only a minority have taken into consideration the impact of extrauterine life. The aim of this study was to assess the normal maturation of VEP in infants born prior to 29 weeks gestational age (GA) and to explore the potential influence of extrauterine life. METHODS: VEP were prospectively recorded in extremely preterm infants, and principal peaks (N0, N1, P1, N2, P2, N3) were identified. The mean of peak-time and percentages of peak appearances were assessed for three GA groups (23/24, 25/26, 27/28 weeks) and four subgroups of increasing postnatal age (PNA), up to 8 weeks after birth. RESULTS: A total of 163 VEP recordings in 38 preterm infants were analyzed. With increasing GA at birth, peak-times decreased. When comparing infants with equal GA but longer extrauterine life, those with the highest PNA demonstrated the shortest VEP peak-times. However, this effect was less present in infants born prior to 25 weeks GA. CONCLUSION: Provided that a certain maturational threshold is reached, extrauterine life appears to accelerate maturation of the visual system in preterm infants.

Implementation and Evaluation of Training for Ultrasound-Guided Vascular Access to Small Vessels Using a Low-Cost Cadaver Model.

OBJECTIVES: Critically ill neonatal and pediatric patients often require central vascular access. Real-time ultrasound guidance for central venous catheterization is beneficial. Because the diameter of central veins is much smaller in neonates than in adults, extensive training is needed to master the visualization and catheterization of central veins in neonates. This study assessed the learning effect of a standardized simulation-based teaching program on ultrasound-guided cannulation in a low-cost cadaver tissue model. DESIGN: This simulation-based prospective study assessed physician competence in the ultrasound-guided central venous catheterization procedure. Analyses were conducted before and after the teaching course. SETTING: Pediatric simulation center at a tertiary care center. SUBJECTS: Staff physicians from the Neonatal ICU and PICUs at the Medical University of Vienna. INTERVENTIONS: Two latex tubes, with internal diameters of 2 and 4 mm, were inserted in parallel into cadaver tissue to mimic vessels and create a model for central venous catheterization. MEASUREMENTS AND MAIN RESULTS: Under ultrasound guidance, each participant attempted to puncture and insert a guide-wire into each of the latex tubes using in-plane and out-of-plane techniques, both before and after the teaching course. The training program was assessed using a questionnaire and a performance checklist. Thirty-nine physicians participated in this study. The rates of failure of guide-wire insertion into 2-mm tubes were significantly lower after than before the teaching course, using both in-plane (p = 0.001) and out-of-plane (p = 0.004) techniques. Teaching, however, did not significantly reduce the insertion failure rate into 4-mm tubes, either in-plane (p = 0.148) or out-of-plane (p = 0.069). The numbers of successful cannulations on the first attempt increased after the teaching in all methods (p = 0.001). CONCLUSIONS: Implementation of a skills training program for ultrasound-guided central venous catheterization in a cadaver tissue model was feasible and cost- and time-effective. The number of attempts until successful cannulation of small vessels (2-mm tube) was significantly lower after than before the standardized teaching program.

The power of N-PASS, aEEG, and BIS in detecting different levels of sedation in neonates: A preliminary study.

BACKGROUND: Sedatives are essential drugs in every intensive care unit in order to ensure the patient's optimal level of comfort. Avoiding conditions of over- and under-sedation is a challenge in a neonatal intensive care setting. Drug administration could be optimized by the concomitant use of objective methods to assess the level of sedation. AIMS: We aimed to look at the ability of different methods (Neonatal Pain, Agitation and Sedation Scale, amplitude-integrated Electroencephalogram, and Bispectral Index), and their combination, in detecting different level of sedation. METHODS: Twenty-seven neonates among whom 17 were receiving sedatives with or without opiate analgesics were monitored using the Neonatal Pain, Agitation and Sedation Scale, the amplitude-integrated Electroencephalogram, and the Bispectral Index. According to the expert opinion of two trained neonatologists, patients were categorized into three groups: no, light, and deep sedation. Four hours of simultaneous assessment of the Neonatal Pain, Agitation and Sedation Scale scores, Burdjalov scores (to summarize the amplitude-integrated Electroencephalogram trace), and Bispectral Index values were considered for the comparative analysis across these groups. RESULTS: All three methods could differentiate patients who were not sedated from those who were deeply sedated: median score 12 and 9, respectively, (95% CI of difference = 1.99-5.99, P = 0.001) for the amplitude-integrated Electroencephalogram Burdjalov score; median 1 and -5, respectively, (95% CI of difference = 2.99-8.00, P = 0.001) for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, (CI of difference = 1.77-22.00, P = 0.043) for the Bispectral Index. However none of them, used alone, was able to differentiate light and deep sedation: median score 10 and 9, respectively, for the amplitude-integrated Electroencephalogram Burdjalov score; median -2 and -5, respectively, for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, for the Bispectral Index. Only the amplitude-integrated Electroencephalogram and the Neonatal Pain, Agitation and Sedation Scale were able to differentiate between the conditions of no sedation and light sedation. Also, according to the area under the curves values, the combination of the Neonatal Pain, Agitation and Sedation Scale with the Burdjalov score derived from the amplitude-integrated Electroencephalogram showed the best accuracy in differentiating light and deep sedation. CONCLUSION: While none of the three methods alone was able to precisely differentiate between different levels of sedation, we suggest that using a combination of amplitude-integrated Electroencephalogram and Neonatal Pain, Agitation and Sedation Scale can be useful to distinguish between light and deep sedation in neonatal patients.

Protein Dynamics in the Reductive Activation of a B12-Containing Enzyme.

B12-dependent proteins are involved in methyl transfer reactions ranging from the biosynthesis of methionine in humans to the formation of acetyl-CoA in anaerobic bacteria. During their catalytic cycle, they undergo large conformational changes to interact with various proteins. Recently, the crystal structure of the B12-containing corrinoid iron-sulfur protein (CoFeSP) in complex with its reductive activator (RACo) was determined, providing a first glimpse of how energy is transduced in the ATP-dependent reductive activation of corrinoid-containing methyltransferases. The thermodynamically uphill electron transfer from RACo to CoFeSP is accompanied by large movements of the cofactor-binding domains of CoFeSP. To refine the structure-based mechanism, we analyzed the conformational change of the B12-binding domain of CoFeSP by pulsed electron-electron double resonance and Förster resonance energy transfer spectroscopy. We show that the site-specific labels on the flexible B12-binding domain and the small subunit of CoFeSP move within 11 Å in the RACo:CoFeSP complex, consistent with the recent crystal structures. By analyzing the transient kinetics of formation and dissociation of the RACo:CoFeSP complex, we determined values of 0.75 µM-1 s-1 and 0.33 s-1 for rate constants kon and koff, respectively. Our results indicate that the large movement observed in crystals also occurs in solution and that neither the formation of the protein encounter complex nor the large movement of the B12-binding domain is rate-limiting for the ATP-dependent reductive activation of CoFeSP by RACo.

Comparison of different types of ultrasound probes for lung ultrasound in neonates-A prospective randomized comparison study.

OBJECTIVE: To determine the effect of different types of probes for lung ultrasound in neonates. DESIGN: Prospective, blinded, randomized, comparative study between 2020 and 2022. SETTING: Single-center study at a third level neonatal unit. PATIENTS: Hemodynamically stable infants with either nasal continuous positive airway pressure, high flow nasal cannula or without respiratory support. INTERVENTION: Lung ultrasound using either an echo or microconvex probe. As control, the linear probe was used. MAIN OUTCOME MEASURES: Primary outcome measure was neonatologist performed lung ultrasound (NPLUS) score. Secondary outcome measures were number of B-Lines, thickness of the pleural line and subjective image quality. Furthermore, correlation between NPLUS results and clinical data was assessed. RESULTS: A total of 1584 video loops from 66 patients, with a mean corrected gestational age of 33.8 weeks (SD 4.23) and weight of 1950g (SD 910), respectively, were analyzed. NPLUS score was estimated lower with the echo- and microconvex probe compared to the linear probe, with a coefficient of -2.95 (p < 0.001) and -1.09 (p = 0.19), respectively. Correlation between the pulse oximetric saturation/fraction of inspired oxygen ratio and NPLUS score was moderately strong and best using the microconvex probe (Spearman's rho = -0.63, p<0.001). CONCLUSION: Our results not only confirm the current recommendations, but also demonstrate the extent of the varying results when different probes are used. The differences we discovered call for caution in interpreting scores, especially in the context of guiding therapies and communicating prognoses. Finally, the correlation between NPLUS score and clinical parameters contributes to validating the use of this diagnostic tool.

Suppression of electron transfer to dioxygen by charge transfer and electron transfer complexes in the FAD-dependent reductase component of toluene dioxygenase.

The three-component toluene dioxygenase system consists of an FAD-containing reductase, a Rieske-type [2Fe-2S] ferredoxin, and a Rieske-type dioxygenase. The task of the FAD-containing reductase is to shuttle electrons from NADH to the ferredoxin, a reaction the enzyme has to catalyze in the presence of dioxygen. We investigated the kinetics of the reductase in the reductive and oxidative half-reaction and detected a stable charge transfer complex between the reduced reductase and NAD(+) at the end of the reductive half-reaction, which is substantially less reactive toward dioxygen than the reduced reductase in the absence of NAD(+). A plausible reason for the low reactivity toward dioxygen is revealed by the crystal structure of the complex between NAD(+) and reduced reductase, which shows that the nicotinamide ring and the protein matrix shield the reactive C4a position of the isoalloxazine ring and force the tricycle into an atypical planar conformation, both factors disfavoring the reaction of the reduced flavin with dioxygen. A rapid electron transfer from the charge transfer complex to electron acceptors further reduces the risk of unwanted side reactions, and the crystal structure of a complex between the reductase and its cognate ferredoxin shows a short distance between the electron-donating and -accepting cofactors. Attraction between the two proteins is likely mediated by opposite charges at one large patch of the complex interface. The stability, specificity, and reactivity of the observed charge transfer and electron transfer complexes are thought to prevent the reaction of reductase(TOL) with dioxygen and thus present a solution toward conflicting requirements.

LED light can falsify pulse oximetry readings via the stroboscopic effect.

Because of its simplicity, pulse oximetry plays a ubiquitous role in neonatology. Its measurements are based on the absorption of light by hemoglobin. Ambient light can affect these values, therefore algorithms are designed to compensate for constant ambient light. Modern light-emitting diodes often flicker at a very high frequency. Such flickering ambient light can lead to significant measurement errors in saturation. To present a novel way in which light-emitting diodes influence the function of pulse oximeters and to demonstrate mathematically that a stroboscopic effect may well be responsible for this disturbance. Using publicly available data, a mathematical model of a pulse oximeter with a calibration curve and a proprietary measurement algorithm was created. This was used to simulate saturation measurements in flickering ambient light. To do this, photopletysmograms for red and infrared light at 98% oxygen saturation were mathematically superimposed on the light emission from an examination lamp used in the intensive care unit. From these results, presumable saturation measurements from a pulse oximeter were extrapolated. The light-emitting diodes in the examination lamp flicker at 207 Hz. The pulsating light from the light-emitting diodes causes superimposition of the photoplethysmogram due to the stroboscopic effect. With increasing brightness, the saturation dropped to 85% and the pulse rate to 108 bpm. The pulsed light of light-emitting diodes can distort pulse oximetry measurements. The stroboscopic effect leads to low saturation values, which can lead to the risk of blindness in premature infants due to excessive oxygenation.

Real-Time Intubation and Ventilation Feedback: A Randomized Controlled Simulation Study.

BACKGROUNDS: This study aimed to determine the best educational application of a respiratory function monitor and a video laryngoscope. METHODS: This study was a randomized controlled simulation-based trial, including 167 medical students. Participants had to execute ventilation and intubation maneuvers on a newborn manikin. Participants were randomized into 3 groups. In group A (no-access), the feedback devices were not visible but recording. In group B (supervisor-access), the feedback devices were visible to the supervisor only. In group C (full-access), both the participant and the supervisor had visual access. RESULTS: The two main outcome variables were the percentage of ventilations within the tidal volume target range (4-8mL/kg) and the number of intubation attempts. Group C achieved the highest percentage of ventilations within the tidal volume target range (full-access 63.6%, supervisor-access 51.0%, no-access 31.1%, P < .001) and the lowest mask leakage (full-access 34.9%, supervisor-access 46.6%, no-access 61.6%; A to B: P < .001, A to C: P < .001, B to C: P = .003). Overall, group C achieved superior ventilation quality regarding primary and secondary outcome measures. The number of intubation attempts until success was lowest in the full-access group (full-access: 1.29, supervisor-access: 1.77, no-access: 2.43; A to B: P = .001, A to C: P < .001, B to C: P = .015). CONCLUSIONS: Our findings confirm that direct visual access to feedback devices for supervisor and trainees alike considerably benefits outcomes and can contribute to the future of clinical education.

Incidence of Post-extubation Stridor in Infants With Cuffed vs. Uncuffed Endotracheal Tube: A Retrospective Cohort Analysis.

Background: Endotracheal intubation is a common procedure in Neonatal Intensive Care. While cuffed endotracheal tubes (ETT) are the standard of care in adults and children, their use in infants is controversial. The aim of this study was to compare the incidence of post-extubation stridor between uncuffed and cuffed ETTs in infants. We further evaluated the safety of cuffed ETTs in infants with a bodyweight between 2 and 3 kg and performed baseline analysis on development of subglottic stenosis. Methods: In this retrospective study, we screened all infants admitted to two NICUs of the Medical University of Vienna between 2012 and 2019.The study cohort was screened twice: In the first screening we selected all infants who underwent the first intubation when attaining a bodyweight >2 kg (but <6 kg) to analyze the incidence of post-extubation stridor and only considered the first intubation of each included infant. Post-extubation stridor was defined as the administration of either epinephrine aerosol or any corticosteroid within 6 h post-extubation. In the second screening we searched for all infants diagnosed with acquired severe subglottic stenosis during the study period regardless their bodyweight and numbers of intubations. Results: A total of 389 infants received at least one intubation during the study period. After excluding infants who underwent the first intubation below a bodyweight of 2 kg, 271 infants remained for final analysis with an average gestational age of 38.7 weeks at the time of intubation. Among those, 92 (33.9%) were intubated with a cuffed and 179 (66.1%) with an uncuffed ETT. Seven infants (2.6%) developed a clinically significant stridor: five of those were intubated with a cuffed and two with an uncuffed ETT (71.4 vs. 28.6%, p = 0.053). All of them had a bodyweight >3 kg at the time of intubation. Infants who developed subglottic stenosis were more often intubated with an uncuffed ETT. Conclusion: In this study, no difference in the incidence of post-extubation stridor between cuffed and uncuffed ETTs in infants with a bodyweight from 2 to 6 kg could be found. The use of uncuffed ETTs does not exhibit higher risk for the acquired subglottic stenosis in this cohort.