CT dose reduction factors in the thousands using X-ray phase contrast

Phase-contrast X-ray imaging can improve the visibility of weakly absorbing objects (e.g. soft tissues) by an order of magnitude or more compared to conventional radiographs. Previously, it has been shown that combining phase retrieval with computed tomography (CT) can increase the signal-to-noise ratio (SNR) by up to two orders of magnitude over conventional CT at the same radiation dose, without loss of image quality. Our experiments reveal that as radiation dose decreases, the relative improvement in SNR increases. We discovered this enhancement can be traded for a reduction in dose greater than the square of the gain in SNR. Upon reducing the dose 300 fold, the phase-retrieved SNR was still almost 10 times larger than the absorption contrast data. This reveals the potential for dose reduction factors in the tens of thousands without loss in image quality, which would have a profound impact on medical and industrial imaging applications

Clinical aspects of incorporating cord clamping into stabilisation of preterm infants

Fetal to neonatal transition is characterised by major pulmonary and haemodynamic changes occurring in a short period of time. In the international neonatal resuscitation guidelines, comprehensive recommendations are available on supporting pulmonary transition and delaying clamping of the cord in preterm infants. Recent experimental studies demonstrated that the pulmonary and haemodynamic transition are intimately linked, could influence each other and that the timing of umbilical cord clamping should be incorporated into the respiratory stabilisation. We reviewed the current knowledge on how to incorporate cord clamping into stabilisation of preterm infants and the physiological-based cord clamping (PBCC) approach, with the infant's transitional status as key determinant of timing of cord clamping. This approach could result in optimal timing of cord clamping and has the potential to reduce major morbidities and mortality in preterm infants

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

Introduction Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases

Transitional circulation and hemodynamic monitoring in newborn infants

Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed. Impact: Transitional circulation can vary markedly between infants. There are alterations in preload, contractility, and afterload during the transition of circulation after birth in term and preterm infants. Hemodynamic monitoring tools and technology during neonatal transition and utilization of bedside echocardiography during the neonatal transition are increasingly recognized. Understanding the cardiovascular physiology of transition can help clinicians in making better decisions while managing infants with hemodynamic compromise. The objective assessment of cardio-respiratory transition and understanding of physiology in normal and disease states have the potential of improving short- and long-term health outcomes

Physiological-Based Cord Clamping:When the Baby Is Ready for Clamping

Background: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the survival and well-being of preterm infants. While initially the rationale behind delaying clamping was to facilitate increased placental transfusion, research has unveiled additional hemodynamic benefits. Summary: Experimental studies have demonstrated improved circulatory transition when clamping is postponed until the lungs are adequately aerated. This suggests that infants requiring assistance during the transition phase may benefit from stabilization while still attached to the cord. The Aeration, Breathing, and then Clamping (ABC) project aimed to translate these experimental findings into clinical practice. Key Message: In this review, we will discuss the insights gained and lessons learned from the project's implementation

Comparison of Two Respiratory Support Strategies for Stabilization of Very Preterm Infants at Birth: A Matched-Pairs Analysis

Objective: Respiratory support for stabilizing very preterm infants at birth varies between centers. We retrospectively compared two strategies that involved either increasing continuous positive airway pressures (CPAP), or increasing oxygen supplementation.Methods: Matched-pairs of infants (<28 weeks of gestation) were born either at the Leiden University Medical Center [low-pressure: CPAP 5–8 cmH2O and/or positive pressure ventilation (PPV) and fraction of inspired oxygen (FiO2) 0.3–1.0; n = 27], or at the University Hospital of Cologne (high-pressure: CPAP 12–35 cmH2O, no PPV and FiO2 0.3–0.4; n = 27). Respiratory support was initiated non-invasively via facemask at both units. Infants (n = 54) were matched between centers for gestational age and birth weight, to compare physiological and short-term clinical outcomes.Results: In the low-pressure group, 20/27 (74%) infants received 1–2 sustained inflations (20, 25 cm H2O) and 22/27 (81%) received PPV (1:19–3:01 min) using pressures of 25–27 cm H2O. Within 3 min of birth [median (IQR)], mean airway pressures [12 (6–15) vs. 19 (16–23) cmH2O, p < 0.001] and FiO2 [0.30 (0.28–0.31) vs. 0.22 (0.21–0.30), p < 0.001] were different in low- vs. high-pressure groups, respectively. SpO2 and heart rates were similar. After 3 min, higher FiO2 levels [0.62 (0.35–0.98) vs. 0.28 (0.22–0.38), p = 0.005] produced higher SpO2 levels [77 (50–92) vs. 53 (42–69)%, p < 0.001] in the low-pressure group, but SpO2/FiO2 and heart rates were similar. While intubation rates during admission were significantly different (70 vs. 30%, p = 0.013), pneumothorax rates (4 vs. 19%, p = 0.125) and the occurrence of spontaneous intestinal perforations (0 vs. 15%, p = 0.125) were similar between groups.Conclusion: Infants (<28 weeks) can be supported non-invasively at birth with either higher or lower pressures and while higher-pressure support may require less oxygen, it does not eliminate the need for oxygen supplementation. Future studies need to examine the effect of high pressures and pressure titration in the delivery room

High vs. Low Initial Oxygen to Improve the Breathing Effort of Preterm Infants at Birth: Study Protocol for a Randomized Controlled Trial

Background: Although most preterm infants breathe at birth, their respiratory drive is weak and supplemental oxygen is often needed to overcome hypoxia. This could in turn lead to hyperoxia. To reduce the risk of hyperoxia, currently an initial low oxygen concentration (21–30%) is recommended during stabilization at birth, accepting the risk of a hypoxic period. However, hypoxia inhibits respiratory drive in preterm infants. Starting with a higher level of oxygen could lead to a shorter duration of hypoxia by stimulating breathing effort of preterm infants, and combined with subsequent titration based on oxygen saturation, prolonged hyperoxia might be prevented.Study design: This multi-center randomized controlled trial will include 50 infants with a gestational age between 24 and 30 weeks. Eligible infants will be randomized to stabilization with an initial FiO2 of either 1.0 or 0.3 at birth. Hereafter, FiO2 will be titrated based on the oxygen saturation target range. In both groups, all other interventions during stabilization and thereafter will be similar. The primary outcome is respiratory effort in the first 5 min after birth expressed as average minute volume/kg. Secondary outcomes include inspired tidal volumes/kg, rate of rise to maximum tidal volume/kg, percentage of recruitment breaths with tidal volumes above 8 mL/kg, duration of hypoxia and hyperoxia and plasma levels of markers of oxidative stress (8-iso-prostaglandin F2α).Discussion: Current resuscitation guidelines recommend oxygen titration if infants fail to achieve the 25th percentile of the SpO2 reference ranges. It has become clear that, using this approach, most preterm infants are at risk for hypoxia in the first 5 min after birth, which could suppress the breathing effort. In addition, for compromised preterm infants who need respiratory support at birth, higher SpO2 reference ranges in the first minutes after birth might be needed to prevent prolonged hypoxia. Enhancing breathing effort by achieving an adequate level of oxygenation could potentially lead to a lower incidence of intubation and mechanical ventilation in the delivery room, contributing to a lower risk on lung injury in high-risk preterm infants. Measuring 8-iso-prostaglandin F2α could lead to a reflection of the true amount of oxygen exposure in both study groups

Knee-to-chest flexion manoeuvre to reduce respiratory distress after planned caesarean birth:a feasibility study

Background Planned caesarean section (CS) is a risk factor for neonatal respiratory distress caused by a greater volume of airway liquid in the absence of uterine contractions. Performing a newly conceptualised knee-to-chest flexion (KCF) manoeuvre at birth, mimicking uterine contraction-induced flexion may aid in expelling excess lung liquid. Objectives To test whether performing a KCF manoeuvre at birth is feasible in infants born after planned CS and to test whether KCF leads to visible expulsion of lung liquid. Methods Single-centre prospective interventional study in term infants born by planned CS at Leiden University Medical Centre, Netherlands. KCF was performed for a maximum of 45 s. Baseline characteristics were collected, primary outcome was ability to perform KCF and secondary outcome was any visible expulsion of fluid. Results In 39 infants (mean (SD) gestational age 38.0 (0.7) weeks, birth weight 3537 (440) g), KCF could be performed in 21/39 (54%), whereas 18/39 (46.2%) starting vigorous breathing before KCF could be performed. Notably, visible lung liquid expulsion occurred in 9/21 (43%) infants. KCF duration averaged 29 (18) s. In 13/21 (62 %), KCF was not performed as per standard operating procedure. No adverse events were reported. Conclusion It is feasible to perform KCF at birth in a large proportion of term infants born by planned CS, with visible expulsion of liquid in a significant proportion of these infants. Training healthcare providers to perform a standardised KCF could increase feasibility and success. Further studies are needed to assess feasibility and effectiveness of KCF.</p

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease