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Study Objective: Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients. Therefore, this study aimed to describe current anesthesia practices across Europe for infants undergoing surgery for NEC., Design: Cross-sectional survey study., Participants: Anesthesiologists working in centers where surgery for NEC is performed across Europe., Measurements: A 46-item questionnaire assessing protocols for anesthesia practice, preoperative care, intraoperative care, postoperative care, and the respondent's opinion on the adequacy of anesthetic care for patients with NEC in their center., Main Results: Out of the 173 responding anesthesiologists from 31 countries, approximately a third had a written standard protocol for anesthetic care in infants. Three quarters of the respondents screened all patients with NEC preoperatively, and a third structurally performed preoperative multidisciplinary consultation. For induction of general anesthesia, most respondents opted for intravenous anesthesia (n = 73, 43%) or a combination of intravenous and inhalation anesthesia (n = 57, 33%). For intravenous induction, they mostly used propofol (n = 58, 44%), followed by midazolam (n = 43, 33%) and esketamine (n = 42, 32%). For maintenance of anesthesia, inhalation anesthetic agents were more commonly used (solely: n = 71, 41%; in combination: n = 37, 22%), almost exclusively with sevoflurane. Postoperative analgesics mainly included paracetamol and/or morphine. Sixty percent of the respondents (n = 104) considered their anesthetic care for patients with NEC adequate. Suggestions for further improvement mainly revolved around monitoring, protocols, and collaboration., Conclusions: Anesthesia practice for infants undergoing surgery for NEC was highly variable. Most respondents considered the provided anesthetic care for patients with NEC adequate, but also recognized opportunities for further improvement, especially with regards to monitoring, protocols, and interdisciplinary collaboration., Competing Interests: Declaration of competing interest LS received departmental funding for research from Merck / MSD. The other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional and ultrafast spectral Doppler during anesthesia and their potential to show the effect of anesthesiologic procedures on cerebral blood flow velocities, in relation to blood pressure and cerebral oxygenation in infants undergoing inguinal hernia repair., Methods: A single-center prospective observational cohort study in infants up to six months of age. We evaluated conventional and ultrafast spectral Doppler cerebral ultrasound measurements in terms of number of successful measurements during the induction of anesthesia, after sevoflurane induction, administration of caudal analgesia, a fluid bolus and emergence of anesthesia. Cerebral blood flow velocity was quantified in pial arteries using conventional spectral Doppler and in the cerebral cortex using ultrafast Doppler by peak systolic velocity, end diastolic velocity and resistivity index., Results: Twenty infants were included with useable conventional spectral Doppler images in 72/100 measurements and ultrafast Doppler images in 51/100 measurements. Intraoperatively, the success rates were 53/60 (88.3%) and 41/60 (68.3%), respectively. Cerebral blood flow velocity increased after emergence for both conventional (end diastolic velocity, from 2.01 to 2.75 cm/s, p < 0.001) and ultrafast spectral Doppler (end diastolic velocity, from 0.59 to 0.94 cm/s), whereas cerebral oxygenation showed a reverse pattern with a decrease after the emergence of the infant (85% to 68%, p < 0.001)., Conclusion: It is possible to quantify cortical blood flow velocity during general anesthesia using conventional and ultrafast spectral Doppler cerebral ultrasound. Cerebral blood flow velocity and blood pressure decreased, while regional cerebral oxygenation increased during general anesthesia. Ultrafast spectral Doppler ultrasound offers novel insights into perfusion within the cerebral cortex, unattainable through conventional spectral ultrasound. Yet, ultrafast Doppler is curtailed by a lower success rate and a more rigorous learning curve compared to conventional method., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier Inc.)

Background: Infants admitted to the intensive care unit experience numerous early-life stressors, which may have long-term effects on hypothalamic-pituitary-adrenal axis functioning., Aims: To determine the effects of intensive care treatment and related exposure to stress, pain, and opioids in infancy on cortisol levels in childhood and adolescence., Study Design: Cross-sectional study., Subjects: Children and adolescents aged 8 to 18 years with a history of intensive care treatment in infancy and healthy controls. The intensive care treatment cohort consisted of four subgroups with varying levels of exposure to stress, pain, and opioids in infancy. They received either mechanical ventilation, extracorporeal membrane oxygenation, major surgery, or excochleation of a giant congenital melanocytic nevus., Outcome Measures: Between-group differences in stress reactivity to a study visit consisting of pain threshold testing and an MRI examination and diurnal cortisol levels, as measured in saliva., Results: After adjustment for age, sex, and gestational age, the diurnal cortisol output (AUCg) in the overall intensive care group (N = 76) was 18 % (approximately 1000 nmol/L) (95 % CI [-31 %, -3 %], P = 0.022) lower than that in the control group (N = 67). Cortisol awakening response, diurnal decline, and stress reactivity neither differed significantly between the overall intensive care group and control group, nor between the intensive care subgroups and control group., Conclusion: Children and adolescents with a history of intensive care treatment in infancy have similar cortisol profiles to those of healthy controls, except for an 18 % lower diurnal cortisol output. The clinical relevance of this reduction is yet to be determined., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Stress during treatment at the Neonatal Intensive Care Unit (NICU) has long-term negative consequences on preterm infants' development., Aims: We developed an instrument suited to validly determine the cumulative stress exposure for preterm infants in a NICU., Study Design: This survey study made use of two consecutive questionnaires., Subjects: NICU nurses and physicians from the nine NICUs in the Netherlands., Outcome Measures: First, respondents rated the relevance of 77 items encompassing potentially stressful procedures, commented on their comprehensibility and the comprehensiveness of the list. We calculated the content validity per item (CVI-I) and included only the relevant items in a second questionnaire in which the participants rated the stressfulness from 0 (not stressful) to 10 (extremely stressful). A stressfulness index - representing the median score - was calculated for each included item., Results: Based on the CVI-I of the 77 items, step 1 resulted in 38 items considered relevant to quantify stress in preterm infants during the first 28 days of life. This list of 38 items exists of 34 items with a CVI-I if 0.78 or higher, one of these items was split into two items, and three items were added to improve comprehensiveness. The stressfulness index ranged from five to nine., Conclusions: The NeO-stress score consists of stressful items including their severity index and was developed to determine cumulative stress exposure of preterm infants. Evaluating the cross-cultural validity, correlating it to behavioural and biological stress responses, and evaluating its ability to predict preterm infants at risk for the negative effects following stress might expand the possibilities for this instrument., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

Pain in newborn children should be prevented due to negative short- and long-term consequences. A good understanding of the development of the nociceptive system in newborns is necessary to enable optimal pain assessment, and most importantly to treat and prevent pain adequately in neonates. So far, preclinical juvenile animal studies have led to a tremendous amount of information regarding the development of the nociceptive system. In addition, they have made clear that the developmental stage of the nociceptive system may influence the mechanism of action of different classes of analgesics. Age specific analgesic therapy, based on post-menstrual age, should therefore be considered by incorporating information on the developmental stages of the nociceptive system in combination with knowledge from pharmacokinetic and -dynamic studies in neonates., (© 2019 Elsevier Ltd. All rights reserved.)

Purpose: Haploinsufficiency of USP7, located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling., Methods: We report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency., Results: The clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination., Conclusion: The consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.