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Objectives: To describe the typical clinical course of reversible persistent pulmonary hypertension of the newborn (PPHN) from perinatal etiologies and compare that with the clinical course of PPHN due to underlying fetal developmental etiologies., Study Design: This was a single-center, retrospective cohort study of liveborn newborns either born or transferred to our facility for higher level of care between 2015 and 2020 with gestational age ≥35 weeks and a clinical diagnosis of PPHN in the electronic health record. Newborns with complex congenital heart disease and congenital diaphragmatic hernia were excluded. Using all data available at time of collection, newborns were stratified into 2 groups by PPHN etiology - perinatal and fetal developmental causes. Primary outcomes were age at initiation, discontinuation, and total duration of extracorporeal life support, mechanical ventilation, supplemental oxygen, inhaled nitric oxide, inotropic support, and prostaglandin E1. Our secondary outcome was age at echocardiographic resolution of pulmonary hypertension. Groups were compared by t-test. Time-to-event Kaplan Meier curves described and compared (log-rank test) discontinuation of each therapy., Results: Sixty-four (72%) newborns had perinatal etiologies whereas 24 (28%) had fetal developmental etiologies. The resolution of perinatal PPHN was more rapid compared with fetal developmental PPHN. By 10 days of age, more neonates were off inotropes (98% vs 29%, P < .01), decannulated from extracorporeal life support (100% vs 0%, P < .01), extubated (75% vs 37%, P < .01), and had echocardiographic resolution of PH (35% vs 7%, P = .02)., Conclusions: An atypical PPHN course, characterized by persistent targeted therapies in the second week of life, warrants further work-up for fetal developmental causes., Competing Interests: Declaration of Competing Interest Funding: Supported by the National Institutes of Health (T32HL160508-01A1 [S.M.T.], P01 HL146369 [J.R.F.]). The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mate recognition is paramount for sexually reproducing animals, and many insects rely on cuticular hydrocarbons (CHCs) for close-range sexual communication. To ensure reliable mate recognition, intraspecific sex pheromone variability should be low. However, CHCs can be influenced by several factors, with the resulting variability potentially impacting sexual communication. While intraspecific CHC variability is a common phenomenon, the consequences thereof for mate recognition remain largely unknown. We investigated the effect of CHC variability on male responses in a parasitoid wasp showing a clear-cut within-population CHC polymorphism (three distinct female chemotypes, one thereof similar to male profiles). Males clearly discriminated between female and male CHCs, but not between female chemotypes in no-choice assays. When given a choice, a preference hierarchy emerged. Interestingly, the most attractive chemotype was the one most similar to male profiles. Mixtures of female CHCs were as attractive as chemotype-pure ones, while a female-male mixture negatively impacted male responses, indicating assessment of the entire, complex CHC profile composition. Our study reveals that the evaluation of CHC profiles can be strict towards 'undesirable' features, but simultaneously tolerant enough to cover a range of variants. This reconciles reliable mate recognition with naturally occurring variability.

The structure and chemical state of heterogeneous catalysts are closely related to their operational stability. Knowing these relationships as precisely as possible is thus essential for further catalyst development. This work focuses on the deactivation of a Cu/ZnO/ZrO 2 -type catalyst for methanol synthesis. Experiments were performed in a parallel setup, with which time-dependent changes in the catalyst material can be observed. Elucidation of potential deactivation pathways is described for catalyst aging at different times on stream (0, 50, 935 h). Data from X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, N 2 physisorption, and transmission electron microscopy measurements reveal that sintering of Cu 0 domains and restructuring within ZnO domains mainly contribute to deactivation. Subsequent reactivation by reduction (in H 2 /N 2 ) reverts the observed structural changes only to a limited extent. Moreover, this work highlights the participation of ZrO 2 as a promoter and reveals redispersion of zirconia after initial reduction.

Background: Neonates with persistent pulmonary hypertension of the newborn (PPHN) can present with hypoxia and right ventricular dysfunction with resultant inadequate oxygen delivery and end-organ damage. This study describes the use of prostaglandin-E1 (PGE) for ductal patency to preserve right ventricular systolic function and limit afterload in newborns with PPHN., Methods: This is a retrospective cohort study that follows the hemodynamics, markers of end-organ perfusion, length of therapeutics, and echocardiographic variables of 57 newborns who used prostglandin-E1 in the setting of PPHN., Results: Tachycardia, lactic acidosis, and supplemental oxygen use improved following PGE initiation. Fractional area change (FAC), to assess right ventricular systolic function, and pulmonary arterial acceleration time indexed to right ventricular ejection time (PAAT/RVET), to assess right ventricular afterload, also improved over three time points relative to PGE use (before, during, and after)., Conclusions: Overall, we described the safety and utility of PGE in newborns with severe PPHN for stabilization while allowing natural disease progression., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Extremely premature infants are at risk for circulatory collapse or respiratory failure that are often treated with hydrocortisone (HC); however, there is no information on the metabolic consequences of this therapy., Methods: Longitudinal urine samples from infants <28 weeks gestation in the Trial of Late Surfactant were analyzed by untargeted UHPLC:MS/MS. Fourteen infants who received a tapering course of HC beginning at 3 mg/kg/day for ≥9 days were compared to 14 matched control infants. A secondary cross-sectional analysis by logistic regression used urines from 314 infants., Results: Of 1145 urinary metabolites detected, abundance of 219, representing all the major biochemical pathways, changed at p < 0.05 in the HC-treated group with 90% decreasing; 3 cortisol derivatives increased ~2-fold with HC therapy. Only 11% of regulated metabolites remained responsive at the lowest HC dose. Regulated metabolites included two steroids and thiamin that are associated with lung inflammation in infants. HC responsiveness was confirmed in 57% of metabolites by cross-sectional analysis., Conclusions: HC treatment of premature infants influenced in a dose-dependent manner abundance of 19% of identified urinary metabolites of diverse biochemical systems, primarily reducing concentrations. These findings indicate that exposure to HC reversibly impacts the nutritional status of premature infants., Impact: Hydrocortisone treatment of premature infants with respiratory failure or circulatory collapse alters levels of a subset of urinary metabolites representing all major biochemical pathways. This is the first description of the scope, magnitude, timing and reversibility of metabolomic changes in infants in response to hydrocortisone, and it confirms corticosteroid regulation of three biochemicals that are associated with lung inflammatory status. The findings indicate a dose-dependency of hydrocortisone for metabolomic and anti-inflammatory effects, that prolonged therapy may lower the supply of many nutrients, and that monitoring concentrations of cortisol and inflammation markers may be a useful clinical approach during corticosteroid therapy., (© 2023. The Author(s).)

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential for sustaining premature infants until they transition to enteral feeds, but there is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born <29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs. enteral feeds at p < 0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants in a longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with the initiation of enteral feeds. These infants had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting the nutritional benefit of an enteral feeding regimen.

A multidisciplinary team is needed to optimally care for infants with congenital heart disease (CHD). Different compositions of teams trained in cardiology, critical care, cardiothoracic surgery, anesthesia, and neonatology have been identified as being primarily responsible for perioperative care of this high-risk population in dedicated cardiac intensive care units (CICUs). Although the specific role of cardiac intensivists has become more well defined over the past two decades, the responsibilities of neonatologists remain highly variable in the CICU with neonatologists providing care along with a unique spectrum of primary, shared, or consultative care. The neonatologist can function as the primary physician and assume all or share responsibility with the cardiac intensivists for the management of infants with CHD. A neonatologist can provide care as a secondary consultant physician in a supportive role for the primary CICU team. Additionally, neonates with CHD can be mixed with older children in a CICU, cohorted in a dedicated space within the CICU or placed in a stand-alone infant CICU without older children. Although variations exist between centers on which model of care is deployed and the location within a CICU, characterization of current practice patterns represents the initial step required to determine optimal best practices to improve the quality of care for neonates with cardiac disease. In this manuscript, we present four models utilized in the United States in which the neonatologist provides neonatal-cardiac-focused care in a dedicated CICU. We also outline the different permutations of location where neonates can be cared for in dedicated pediatric/infant CICUs.

Despite the increase in therapeutic options, parenteral prostacyclins remain the cornerstone in the medical management of pulmonary arterial hypertension (PAH). While the use of parenteral prostacyclins in pediatric patients is well documented, less is known about alternative drug delivery methods such as enteral administration. Given that parenteral routes of prostacyclin administration (IV or SC) are invariably accompanied by complicated logistics and lifestyle compromises, enteral prostacyclin administration represents an attractive treatment option. Selexipag (Uptravi®) was approved for adults PAH in 2015. There is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population. We report 11 pediatric PAH patients who underwent this transition, in which 10 had complete cardiac catheterization data before and following the transition to selexipag. All patients/families reported an improvement in quality of life, and the transitions occurred without adverse effects. However, 3 of the 11 (27%) did not tolerate the transition; two for worsening hemodynamics, and one for acute right ventricular failure in the setting of an intercurrent illness. In addition, the transition to selexipag was associated with a modest increase in pulmonary vascular resistance index (6/10) and decrease in cardiac index (6/10) in some patients. Selexipag use in pediatric PAH represents a significant addition to our therapeutic arsenal, and its use provides a meaningful improvement in quality of life compared with other prostacyclin formulations. However, when goals of care include aggressive disease management, a decision between improved quality of life and possible adverse outcomes must be considered, and its substitution should include cautious, close, long-term follow-up., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Congenital heart disease (CHD) and prematurity are the leading causes of infant mortality in the United States. Importantly, the combination of prematurity and CHD results in a further increased risk of mortality and significant morbidity. The key factors in these adverse outcomes are not well understood, but likely include maternal-fetal environment, perinatal and neonatal elements, and challenging postnatal care. Preterm neonates with CHD are born with "double jeopardy": not only do they experience challenges related to immaturity of the lungs, brain, and other organs, but they also must undergo treatment for cardiac disease. The role of the neonatologist caring for preterm infants with CHD has changed with the evolution of the field of pediatric cardiac critical care. Increasingly, neonatologists invested in the cardiovascular care of the newborn with CHD engage at multiple stages in their course, including fetal consultation, delivery room management, preoperative care, and postoperative treatment. A more comprehensive understanding of prematurity and CHD may inform clinical practice and ultimately improve outcomes in preterm infants with CHD. In this review, we discuss the current evidence surrounding neonatal and cardiac outcomes in preterm infants with CHD; examine the prenatal, perinatal, and postnatal factors recognized to influence these outcomes; identify knowledge gaps; consider research and clinical opportunities; and highlight the ways in which a neonatologist can contribute to the care of preterm infants with CHD., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: Repeated computed tomography (CT) is essential for diagnosis, surgical planning and follow-up in patients with middle and inner ear pathology. Dose reduction to "as low as diagnostically acceptable" (ALADA) is preferable but challenging. We aimed to compare the diagnostic quality of images of subtle temporal bone structures produced with low doses (LD) and reference protocols (RP)., Methods: Two formalin-fixed human cadaver heads were scanned using a 64-slice CT scanner and cone-beam CT (CBCT). The protocols were: RP (120 kV, 250 mA, CTDIvol 83.72 mGy), LD1 (100 kV, 80 mA, CTDIvol 26.79 mGy), LD2 (100 kV, 35 mA, CTDIvol 7.66 mGy), LD3 (80 kV, 40 mA, CTDIvol 4.82 mGy), and CBCT standard protocol. Temporal bone structures were assessed using a 5-point scale., Results: A median score of ≥2 was achieved with protocols such as the tendons of m. tensor tympani (RP/LD1/LD2/CBCT) and m. stapedius (CBCT), the incudostapedial joint (RP/LD1/CBCT), the incudomalleolar joint (RP/LD1/LD2/CBCT), the stapes feet (RP/LD1/CBCT), the stapes head (RP/LD1/LD2/CBCT), the tympanic membrane (RP/LD1/LD2/CBCT), the lamina spiralis ossea (none), the chorda tympani (RP/LD1/CBCT), and the modiolus (RP/LD1/LD2/CBCT). Adaptive statistical iterative reconstructions did not show advantages over the filtered back projection., Conclusions: LD protocols using a CTDIvol of 7.66 mGy may be sufficient for the identification of temporal bone structures.