Successful therapy of a newborn with Stenotrophomonas maltophilia nosocomial pneumonia with cefiderocol.

Cefiderocol is a new siderophore-beta-lactam antibiotic used for the treatment of severe multidrug-resistant infections like sepsis, hospital-acquired and ventilator-associated pneumonia in adults, but there are only single reports on its use in the neonatal population. We describe the successful cefiderocol treatment of a newborn with pneumogenic sepsis due to Stenotrophomonas maltophilia.

Skin Transillumination Improves Peripheral Vein Cannulation by Residents in Neonates: A Randomized Controlled Trial.

INTRODUCTION: Establishing peripheral vein access is challenging for pediatric residents and a painful procedure for neonates. We assessed the efficacy of a red light-emitting diode transilluminator during peripheral vein catheter insertion performed by pediatric residents. METHODS: Patients were stratified by current weight (≤1,500 g, >1,500 g) and randomized to the transillumination or the control group. The first three attempts were performed by pediatric residents, followed by three attempts by a neonatologist. The primary outcome was success at first attempt. Secondary comparisons included time to successful insertion and overall success rates of residents and neonatologists. RESULTS: A total of 559 procedures were analyzed. The success rate at resident's first attempt was 44/93 (47%) with transillumination versus 44/90 (49%) without transillumination (p = 0.88) in the strata ≤1,500 g and 103/188 (55%) with transillumination versus 64/188 (34%) without transillumination in the strata >1,500 g (p < 0.001). The overall success rate for residents was 86% in the transillumination versus 73% in the control group in the strata >1,500 g (p = 0.003) but not different in the strata ≤1,500 g (78/93 [84%] vs. 72/90 [80%], p = 0.57). There was no effect when the experience level of residents exceeded 6 months. Neonatologists' overall success rate and time to successful cannulation did not differ significantly in both weight strata. CONCLUSION: Transillumination improves the first-attempt success rate of peripheral vein cannulation performed by pediatric residents in neonates >1,500 g, while no benefit was found in infants ≤1,500 g.

Excessive sodium supplementation but not fluid load is correlated with overall morbidity in extremely low birth weight infants.

Objectives: Sodium homeostasis in extremely low birth weight (ELBW) infants is critical. While a lack of sodium delays growth, excessive supplementation increases morbidity. Methods: We performed a single-center retrospective study on sodium and fluid management during the first 2 weeks of live including all ELBW infants born between June 1, 2017 and May 31, 2019. Results: Forty-seven patients (median GA 26 + 6 weeks, median BW 845 g) were included. Mean sodium intake was above the ESPGHAN recommendation, 4.58 mmol/kg/day during the first 2 days and 1.99 mmol/kg/day during the following period. Incidence of PDA, IVH, and ROP was directly associated with sodium intake (OR 1.6, 1.3, and 1.4, respectively), but not with fluid supplementation. No association to BPD was found. The most important source for inadvertent sodium intake were 0.9% saline given by arterial lines. Sodium supplementation did not correlate directly with serum sodium levels, but a linear regression model combining sodium intake and fluid supplementation was able to predict serum sodium changes 24-48 h in advance (correlation coefficient of 0.294, p < 0.05). Conclusions: Sodium application substantially exceeded ESPGHAN recommendations in ELBW infants. An excess in sodium was associated with an overall increased morbidity, justifying increased efforts to identify inadvertent sodium sources in these patients with the aim to decrease sodium excess.

Effects of liberalising visiting policy and staff education on parental visiting duration in the neonatal unit.

AIM: The effect of different neonatal unit access hour policies on parental visiting duration is unknown. Therefore, we analysed the effects of access hours policies and parental education on parental visiting duration. METHOD: This prospective longitudinal cohort study was carried out in a level III neonatal unit from October 2020 to May 2022. Three cohorts were compared. The baseline cohort included 51 preterm infants with restricted visiting hours (October 2020 to May 2021). Cohort 1 comprised 35 preterm infants after liberalisation of visiting hours (June 2021 to November 2021). Cohort 2 consisted of 26 preterm infants after an educational program was implemented (December 2021 to May 2022). The primary outcome was the mean daily parental visiting duration. RESULTS: Mean maternal visiting duration was 172 (standard deviation, SD ± 49.2), 195 (SD ± 64.4.), and 258 (SD ± 71.1) minutes/day at baseline and in cohorts 1 and 2 (significant increase from baseline and cohort 1 to cohort 2, p < 0.001). Mean paternal visiting duration did not change significantly across the cohorts: 133 (SD ± 47.2), 135 (SD ± 83.5), and 165 (SD ± 71.3) minutes/day. CONCLUSION: Liberalisation of access hours did not increase parental visiting duration. Parental and staff education significantly increased maternal but not paternal visiting duration.

Multidimensional assessment of infant, parent and staff outcomes during a family centered care enhancement project in a tertiary neonatal intensive care unit: study protocol of a longitudinal cohort study.

BACKGROUND: The therapeutic advances and progress in the care for preterm infants have enabled the regular survival of very immature infants. However, the high burden of lifelong sequelae following premature delivery constitutes an ongoing challenge. Regardless of premature delivery, parental mental health and a healthy parent-child relationship were identified as essential prerogatives for normal infant development. Family centered care (FCC) supports preterm infants and their families by respecting the particular developmental, social and emotional needs in the Neonatal Intensive Care Unit. Due to the large variations in concepts and goals of different FCC initiatives, scientific data on the benefits of FCC for the infant and family outcome are sparse and its effects on the clinical team need to be elaborated. METHODS: This prospective single centre longitudinal cohort study enrols preterm infants ≤ 32 + 0 weeks of gestation and/or birthweight ≤ 1500 g and their parents at the neonatal department of the Giessen University Hospital, Giessen, Germany. Following a baseline period, the rollout of additional FCC elements is executed following a stepwise 6-months approach that covers the NICU environment, staff training, parental education and psychosocial support for parents. Recruitment is scheduled over a 5.5. year period from October 2020 to March 2026. The primary outcome is corrected gestational age at discharge. Secondary infant outcomes include neonatal morbidities, growth, and psychomotor development up to 24 months. Parental outcome measures are directed towards parental skills and satisfaction, parent-infant-interaction and mental health. Staff issues are elaborated with particular focus on the item workplace satisfaction. Quality improvement steps are monitored using the Plan- Do- Study- Act cycle method and outcome measures cover the infant, the parents and the medical team. The parallel data collection enables to study the interrelation between these three important areas of research. Sample size calculation was based on the primary outcome. DISCUSSION: It is scientifically impossible to allocate improvements in outcome measures to individual enhancement steps of FCC that constitutes a continuous change in NICU culture and attitudes covering diverse areas of change. Therefore, our trial is designed to allocate childhood, parental and staff outcome measures during the stepwise changes introduced by a FCC intervention program. TRIAL REGISTRATION: Clinicaltrials.gov, trial registration number NCT05286983, date of registration 03/18/2022, retrospectively registered, http://clinicaltrials.gov .

Fluctuations in Oxygen Saturation during Synchronized Nasal Intermittent Positive Pressure Ventilation and Nasal High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants: A Randomized Crossover Trial.

BACKGROUND: Very low birth weight (VLBW) infants on noninvasive ventilation (NIV) experience frequent fluctuations in oxygen saturation (SpO2) that are associated with an increased risk for mortality and severe morbidities. METHODS: In this randomized crossover trial, VLBW infants (n = 22) born 22+3 to 28+0 weeks on NIV with supplemental oxygen were allocated on two consecutive days in random order to synchronized nasal intermittent positive pressure ventilation (sNIPPV) and nasal high-frequency oscillatory ventilation (nHFOV) for 8 h. nHFOV and sNIPPV were set to equivalent mean airway pressure and transcutaneous pCO2. Primary outcome was the time spent within the SpO2 target (88-95%). RESULTS: During sNIPPV, VLBW infants spent significantly more time within the SpO2 target (59.9%) than during nHFOV (54.6%). The proportion of time spent in hypoxemia (22.3% vs. 27.1%) and the mean fraction of supplemental oxygen (FiO2) (29.4% vs. 32.8%) were significantly reduced during sNIPPV, while the respiratory rate (50.1 vs. 42.6) was significantly higher. Mean SpO2, SpO2 above the target, number of prolonged (>1 min) and severe (SpO2 <80%) hypoxemic episodes, parameters of cerebral tissue oxygenation using NIRS, number of FiO2 adjustments, heart rate, number of bradycardias, abdominal distension and transcutaneous pCO2 did not differ between both interventions. CONCLUSIONS: In VLBW infants with frequent fluctuations in SpO2, sNIPPV is more efficient than nHFOV to retain the SpO2 target and to reduce FiO2 exposure. These results demand more detailed investigations into cumulative oxygen toxicities during different modes of NIV over the weaning period, particularly with regard to consequences for long-term outcomes.

Newborn Septic Arthritis-A Rare Presentation of Late-Onset Group B Streptococcal Disease: Case Report and Short Review of the Literature.

Group B Streptococcus (GBS) disease is a leading cause of invasive bacterial infections among neonates. We present the case of an 11-day-old neonate with septic arthritis as a rare presentation of late-onset disease (LOD) with a favorable short-term outcome. GBS is a leading cause of neonatal infection. Early-onset disease (EOD) is defined as infection from birth to 6 days of age, while LOD occurs from 7 days to approximately 3 months of age. EOD is acquired through vertical transmission and can be reduced through application of intrapartum antibiotic prophylaxis (IAP). LOD can be acquired from the mother or from environmental sources, unlikely to be prevented by IAP. The most common presentation of EOD is bacteremia (83%), pneumonia (9%), and meningitis (7%). While the clinical picture in both EOD and LOD frequently resembles in LOD hamatogenous spreading may predispose neonates to present with uncommon organ manifestation other than the classic systemic signs of sepsis, for example, septic arthritis. Herein, we report on the management and outcome of a term neonate with late onset GqBS bacteremia and subtle clinical symptoms of septic monoarthritis.

Photoelectron circular dichroism of O 1s-photoelectrons of uniaxially oriented trifluoromethyloxirane: energy dependence and sensitivity to molecular configuration.

The photoelectron circular dichroism (PECD) of the O 1s-photoelectrons of trifluoromethyloxirane (TFMOx) is studied experimentally and theoretically for different photoelectron kinetic energies. The experiments were performed employing circularly polarized synchrotron radiation and coincident electron and fragment ion detection using cold target recoil ion momentum spectroscopy. The corresponding calculations were performed by means of the single center method within the relaxed-core Hartree-Fock approximation. We concentrate on the energy dependence of the differential PECD of uniaxially oriented TFMOx molecules, which is accessible through the employed coincident detection. We also compare the results for the differential PECD of TFMOx to those obtained for the equivalent fragmentation channel and similar photoelectron kinetic energy of methyloxirane (MOx), studied in our previous work. Thereby, we investigate the influence of the substitution of the methyl group by the trifluoromethyl group at the chiral center on the molecular chiral response. Finally, the presently obtained angular distribution parameters are compared to those available in the literature.

Preeclampsia was a risk factor for pulmonary interstitial emphysema in preterm infants born ≤32 weeks of gestational age.

AIM: This study determined the prenatal and postnatal risk factors for pulmonary interstitial emphysema (PIE) in preterm infants born at up to 32 weeks of gestational age (GA) and their contribution to severe complications. METHODS: We studied 179 preterm infants, who had undergone chest X-rays during the first five days of life at Justus Liebig University Giessen, Germany, between 2016 and 2017. Of these, 33 were retrospectively classified as PIE and 146 as non-PIE. The PIE cases were also matched with 33 non-PIE cases by GA and gender. Risk factors were identified by univariate analyses and multivariable logistic regression. RESULTS: Previously known risk factors for pulmonary interstitial emphysema were confirmed, including GA and birthweight and the associations with adverse outcomes like intraventricular haemorrhage and mortality. We identified preeclampsia and haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome as additional risk factors for PIE (P = .027), and lung impairment was associated with respiratory distress syndrome (P = .001), higher maximum inspired oxygen (P = .014) and needing surfactant (P = .006). CONCLUSION: Preeclampsia and HELLP syndrome were identified as possible additional risk factors for PIE in preterm infants. These conditions should be included in future studies, to identify preterm infants at risk of PIE straight after birth.

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants-"The OPTTIMMAL-Trial"-Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial.

BACKGROUND: Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. METHODS: In this randomized multicenter trial, 216 preterm infants born at 26 + 0-29 + 6 gestational weeks will be allocated to receive a higher (6-8 cmH2O) or a lower (3-5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). DISCUSSION: Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4-8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. TRIAL REGISTRATION: drks.de DRKS00019940 . Registered on March 13, 2020.

Non-Invasive Ventilation in Neonatology.

BACKGROUND: Invasive mechanical ventilation (IMV) has been replaced by early continuous positive airway pressure (CPAP) in the treatment of respiratory distress syndrome (RDS) in preterm infants aiming to reduce the rate of bronchopulmonary dysplasia (BPD). Subsequently, modern non-invasive ventilation strategies (NIV) were introduced into clinical practice with limited evidence of effects on pulmonary and neurodevelopmental outcomes. METHODS: We performed a selective literature search in PubMed including randomized controlled trials (RCT) (n ≥ 200) and meta-analyses published in the field of NIV in neonatology and follow-up studies focusing on long term pulmonary and neurodevelopmental outcomes. RESULTS: Individual studies do not show a significant risk reduction for the combined endpoint death or BPD in preterm infants caused by early CPAP in RDS when compared to primary intubation. One meta-analysis comparing four studies found CPAP significantly reduces the risk of BPD or death (relative risk: 0.91; 95% confidence interval [0.84;0.99]). Nasal intermittent positive pressure ventilation (NIPPV) as a primary ventilation strategy reduces the rate of intubations in infants with RDS (RR: 0.78 [0.64;0.94]) when compared to CPAP but does not affect the rate of BPD (RR: 0.78 [0.58;1.06]). CONCLUSION: Early CPAP reduces the need for IMV and the risk of BPD or death in preterm infants with RDS. NIPPV may offer advantages over CPAP regarding intubation rates. Networking-based follow-up programs are required to assess the effect of NIV on long term pulmonary and neurodevelopmental outcomes.

Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants.

OBJECTIVE: To assess the efficacy of a newly developed system for closed loop control of the fraction of inspired oxygen (FiO2) on variation of arterial (SpO2) and on regional tissue oxygen saturation (StO2) in preterm infants with fluctuations in SpO2. DESIGN: Randomised crossover trial comparing automated (auto) to manual FiO2 adjustment (manual) during two consecutive 24 hours periods using a Sophie infant ventilator (SPO2C). SETTING: Tertiary university medical centre. PATIENTS: Twelve very low birthweight infant (VLBWI) (gestational age (median; IQR): (25; 23-26 weeks); birth weight (mean±SD): (667±134 g); postnatal age (mean±SD): (31.5±14 days)). MAIN OUTCOME MEASURE: Time within SpO2 target range. RESULTS: There was an increase in time within the intended SpO2 target range (88%-96%) during auto as compared with manual mode (77.8%±7.1% vs 68.5%±7.7% (mean±SD), p<0.001) and a decrease in time below the SpO2 target during the auto period (18.1%±6.4% vs 25.6%±7.6%; p<0.01). There was a dramatic reduction in events with an SpO2 <88% with >180 s duration: (2 (0-10) vs 10 (0-37) events, p<0.001) and the need for manual adjustments. The time the infants spent above the intended arterial oxygen range (4.1%±3.8% vs 5.9%±3.6%), median FiO2, mean SpO2 over time and StO2 in the brain, liver and kidney did not differ significantly between the two periods. CONCLUSIONS: Closed-loop FiO2 using SPO2C significantly increased time of arterial SpO2 within the intended range in VLBWI and decreased the need for manual adjustments when compared with the routine adjustment by staff members. StO2 was not significantly affected by the mode of oxygen control.

Early Pulmonary Interstitial Emphysema in Preterm Neonates-Respiratory Management and Case Report in Nonventilated Very Low Birth Weight Twins.

Early pulmonary interstitial emphysema in extreme preterm neonates is closely linked with respiratory distress syndrome and exposure to mechanical ventilation. In severe cases, maintaining adequate gas exchange aiming to avoid further lung damage and other neonatal morbidities associated with systemic/pulmonary hypoperfusion, prolonged hypoxia, and respiratory acidosis can be challenging and requires in-depth knowledge into the pathophysiology of the disease. Herein, we report on very low birth weight twins who developed early pulmonary interstitial emphysema during noninvasive respiratory support. We further review the current evidence from the literature, specifically addressing on possible preventive measures and the respiratory management options of this acute pulmonary disease in high-risk neonates.

Observation of Enhanced Chiral Asymmetries in the Inner-Shell Photoionization of Uniaxially Oriented Methyloxirane Enantiomers.

Most large molecules are chiral in their structure: they exist as two enantiomers, which are mirror images of each other. Whereas the rovibronic sublevels of two enantiomers are almost identical (neglecting a minuscular effect of the weak interaction), it turns out that the photoelectric effect is sensitive to the absolute configuration of the ionized enantiomer. Indeed, photoionization of randomly oriented enantiomers by left or right circularly polarized light results in a slightly different electron flux parallel or antiparallel with respect to the photon propagation direction-an effect termed photoelectron circular dichroism (PECD). Our comprehensive study demonstrates that the origin of PECD can be found in the molecular frame electron emission pattern connecting PECD to other fundamental photophysical effects such as the circular dichroism in angular distributions (CDAD). Accordingly, distinct spatial orientations of a chiral molecule enhance the PECD by a factor of about 10.

Reliability of Pulse Oximetry during Progressive Hypoxia, Cardiopulmonary Resuscitation, and Recovery in a Piglet Model of Neonatal Hypoxic Cardiac Arrest.

BACKGROUND: Pulse oximetry is widely used in intensive care and emergency conditions to monitor arterial oxygenation and to guide oxygen therapy. OBJECTIVE: To study the reliability of pulse oximetry in comparison with CO-oximetry in newborn piglets during progressive hypoxia, cardiac arrest, cardiopulmonary resuscitation (CPR), and after return of spontaneous circulation (ROSC). METHODS: Thirty-three newborn piglets were exposed to hypoxia until asystole occurred and then resuscitated until ROSC. Arterial oxygen saturation was monitored continuously by pulse oximetry (SpO2) with one sensor applied to the wrist of the right forelimb (FL) and another to the thigh of the left hind limb (HL). Arterial functional oxygen saturation (SaO2) was measured at baseline and at predefined intervals during each phase of the experiment. SpO2 was compared with coinciding SaO2 values and bias considered whenever the difference (SpO2 - SaO2) was beyond ±5%. RESULTS: Bias values were lower at the baseline measurements (-3.7 ± 2.3% in FL and -4.1 ± 3.4% in HL) as well as after ROSC (1.5 ± 4.2% in FL and 0.2 ± 4.6% in HL) with higher precision and accuracy than during other experiment phases. During hypoxia induction, cardiac arrest, and CPR, there was a marked decrease in precision and accuracy as well as an increase in bias up to 43 ± 26 and 56 ± 27% in FL and HL, respectively, over a range of SaO2 from 13 to 51%. CONCLUSION: Pulse oximetry showed increased bias and decreased accuracy and precision during marked hypoxemia in a model of neonatal hypoxic cardiac arrest.

Imaging the He2 quantum halo state using a free electron laser.

Quantum tunneling is a ubiquitous phenomenon in nature and crucial for many technological applications. It allows quantum particles to reach regions in space which are energetically not accessible according to classical mechanics. In this "tunneling region," the particle density is known to decay exponentially. This behavior is universal across all energy scales from nuclear physics to chemistry and solid state systems. Although typically only a small fraction of a particle wavefunction extends into the tunneling region, we present here an extreme quantum system: a gigantic molecule consisting of two helium atoms, with an 80% probability that its two nuclei will be found in this classical forbidden region. This circumstance allows us to directly image the exponentially decaying density of a tunneling particle, which we achieved for over two orders of magnitude. Imaging a tunneling particle shows one of the few features of our world that is truly universal: the probability to find one of the constituents of bound matter far away is never zero but decreases exponentially. The results were obtained by Coulomb explosion imaging using a free electron laser and furthermore yielded He2's binding energy of [Formula: see text] neV, which is in agreement with most recent calculations.

Nasal Intermittent Positive Pressure Ventilation for Preterm Neonates: Synchronized or Not?

Although continuous positive airway pressure (CPAP) is an effective strategy to prevent invasive ventilation, failure rates are high and many babies require endotracheal intubation. Prolonged exposure to mechanical ventilation is linked with bronchopulmonary dysplasia and other morbidities. Different techniques of nasal intermittent positive pressure ventilation (NIPPV) have been proposed as an alternative to CPAP. Bilevel NIPPV and conventional mechanical ventilator-driven NIPPV are used in clinical practice. Both methods differ substantially in pressures and cycling times, potentially affecting their mechanism of action. This review focuses on noninvasive ventilation strategies, their physiologic effects, impact on clinical outcome parameters, and effects of synchronization.

Absolute Configuration from Different Multifragmentation Pathways in Light-Induced Coulomb Explosion Imaging.

The absolute configuration of individual small molecules in the gas phase can be determined directly by light-induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X-ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break-up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light-induced CEI.