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In this study, the antennal sense organs of the scavenging isopod Natatolana borealis are described for the first time, based on scanning electron microscope observations. The peduncles of the two pairs of antennae both show the same kind of organization. The sensory organs on the flagellum consist of several kinds of specialized setae possibly having a uni- or plurimodal function. These setae are either specific to one pair of antennae, or common to both pairs. Various types of ornamentation present on the antennae 1, such as teeth, pseudochaetal formations and micropores, may either play a role in grooming or serve to maintain the functional integrity of the antennae 1, which is of great importance for scavenger species such as Natatolana , in which the first antennae seem to be the main chemoreceptor organs. The most important organs, in terms of their number and size (300 mum), are the aesthetascs. These are carried by the flagellum, and seem to play a mainly chemosensitive role. It is hypothesized that the whole of the antennae 1 flagellum may constitute a specialized organ which is involved in chemoreceptive processes. This organ seems to be homologous to the callynophore described in amphipods. Natatolana borealis is endowed with setae of many other kinds. Some of them, the pocilliform setae, have a subapical pore and may have a chemosensitive function, while the bifid setae probably have a plurimodal function; the apical setae constitute the most frontally located chemoreceptor organs in this animal. Other morphologically different setae complete the antennal sensory equipment: these are the tufted setae which probably participate in collecting particles; and the plumose setae, which have a mechanoreceptive function. Some kinds of setae occur in groups, forming a functional unit (tufted setae/digited organ; tufted setae/pocilliform setae). A brief histological study of the antennules showed a rather similar pattern of organization to that observed in other crustacean species. The meaning and the function of the various structures observed here are discussed. Les organes sensoriels antennaires de l'Isopode necrophage Natatolana borealis sont decrits pour la premiere fois a partir d'observations en microscopie elec tronique. Les pedoncules des deux paires d'antennes presentent le meme type d'organisation. Sur le fouet, les organes sensoriels sont constitues par differents types de soies specialisees ayant des fonctions uni ou plurimodales, elles peuvent etre specifiques a une paire d'antennes ou communes aux deux paires d'antennes. Sur les antennes 1, une serie d'ornementations: dents, formations pseudochaetales, micropores, pourraient intervenir dans des fonctions de toilettage ou de maintien de l'integrite fonctionelle des antennes 1, ce qui est tres important pour des especes necrophages telles que Natatolana chez qui les antennes 1 semblent etre le principal organe chemorecepteur. Les organes les plus importants en nombre et en taille (300 mum) sont les aesthetascs. Ils sont portes par le flagelle, leur fonction serait essentiellement chemosensitive. L'hypothese est emise que l'ensemble du flagelle des antennes 1 pourrait constituer un organe specialise dans les processus de chemoreception. Cet organe est considere comme homologue du callynophore decrit chez les Amphipodes. Il existe egalement de nombreuses autres soies. Certaines sont dotees d'un pore subapical et pourraient donc avoir une fonction chemosensitive, ce sont les soies pocilliformes et les soies bifides, qui ont probablement des fonctions plurimodales, et les soies apicales, qui constituent les organes chemorecepteurs les plus avances de l'animal. D'autres soies de morphologies differentes completent l'organisation sensorielle des antennes, il s'agit des soies touffues, intervenant probablement dans la collecte de particules, et des soies plumeuses, ayant des fonctions mechanoreceptives. Certains types de soies sont associees pour former des unites de fonctionnement (soies touffues/organes digites; soies touffues/soies pocilliformes). L'etude histologique sommaire des antennules revele une unite d'organisation par rapport aux observations faites chez d'autres especes de crustaces. La signification et la fonction des differentes structures mises en evidence sont discutees. [ABSTRACT FROM AUTHOR]

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands., Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity., Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25-89). The median length of PICU admission was 5 days (IQR 3-8). The total RSV-related PICU costs are € 3,826,386 in 2021-2022, and € 3,183,888 in 2022-2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection., Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs., Funding: None., Competing Interests: EP, CB, MH, MK, SM, AN, MR, RWA, JvW and GF have no competing interests to declare. LB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100,000 per industrial partner) for investigator initiated studies from AstraZeneca, Sanofi, Janssen, Pfizer, MSD and MeMed Diagnostics. UMCU has received major funding from the Bill and Melinda Gates Foundation. UMCU has received major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in clinical studies sponsored by AstraZeneca, Merck and Pfizer. UMCU received minor funding (€1000–25,000 per industrial partner) for consultation, DSMB membership or invited lectures by Ablynx, Bavaria Nordic, GSK, Novavax, Pfizer, Moderna, Astrazeneca, MSD, Sanofi, Janssen. LB is the founding chairman of the ReSViNET Foundation. JGW has been an investigator for clinical trials sponsored by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen and an investigator for clinical trials funded by IMI/Horizon2020 and ZonMw. All funds have been paid to the institution (UMCU). JGW participated in advisory boards of Janssen and Sanofi and was a speaker at a Sanofi sponsored symposium with fees paid to the institution (UMCU)., (© 2024 The Author(s).)

Background: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass., Methods: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%., Results: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%)., Conclusions: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20., (© 2024. The Author(s).)

In critically ill adults, high plasma cortisol in face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype. From 53 patients (0-36 months), plasma was obtained pre-operatively, intraoperatively and on post-operative day 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (p<0.0001) but no longer thereafter (p<0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (p<0.0001), glucocorticoid-treated patients had suppressed ACTH already intraoperatively (p≤0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally-activated HPA-axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.

Objectives: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission., Design: National prospective cohort study March 2020 to November 2021., Setting: Seven PICUs in the Netherlands., Patients: Children with MIS-C (0-17 yr) admitted to a PICU., Interventions: None., Measurements and Main Results: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found., Conclusions: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated., Competing Interests: Dr. Buddingh’s institution received funding from Leids Universitair Fonds/ Bontiusstichting and ZonMw. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background and Aims: Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines., Methods: We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations., Results: The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4 h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24 h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1 h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins., Conclusion: The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

DOCK2 is a guanine-nucleotide-exchange factor for Rac proteins. Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and production of reactive oxygen species in neutrophils. Since 2015, six unrelated patients with combined immunodeficiency and early-onset severe viral infections caused by bi-allelic loss-of-function mutations in DOCK2 have been described. Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency. Here, we describe a new kindred with four affected siblings harboring a homozygous splice-site mutation (c.2704-2 A > C) in DOCK2. The mutation results in alternative splicing and a complete loss of DOCK2 protein expression. The patients presented with leaky severe combined immunodeficiency or Omenn syndrome. The novel mutation affects EBV-B cell migration and results in NK cell dysfunction similar to previous observations. Moreover, both cytoskeletal rearrangement and reactive oxygen species production are partially impaired in DOCK2-deficient neutrophils.

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement., Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%., Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36 months old., Trial Registration: Dutch Trial Registry ( www.trialregister.nl ): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015-646), current protocol version: July 3, 2017.

Introduction: Children, with their specific vulnerabilities and needs, make up to more than 20% of society, so they are at risk of getting involved in disasters. Are the specialists treating them for medical problems in daily life also capable to deal with them in disaster situations?, Hypothesis/problem: The goals of this study were to evaluate perceived knowledge and capability of tertiary pediatricians to deal with disasters, to identify promoting factors, and to evaluate education need and willingness to work., Methods: A survey looking for demographics, hospital disaster planning, estimated risk and capability for disasters, training, and willingness to work, and a set of six content assessment questions to evaluate knowledge, were presented to emergency pediatricians and pediatric emergency physicians in specialized tertiary centers., Results: The response rate was 51%. Thirty-five percent had disaster training and 53% felt that disaster education should be obligatory in their curriculum. Risk for disasters was estimated from 2.4/10 for nuclear incidents to 7.6/10 for major trauma. Self-estimated capability for these situations ranged from 1.8/10 in nuclear incidents to 7.6/10 in major trauma. Unconditional willingness to work ranged from 37% in nuclear situations to 68% in pandemics. Mean score on the questions was 2.06/6. Training, knowledge of antidote and personal protective equipment (PPE) use, self-estimated capability, and exposure were significant predictors for higher scores. Willingness to work correlated significantly with age, self-estimated capability, and risk estimation. In case of chemical and nuclear incidents, there was correlation with knowledge on the use of decontamination, PPE, and radio-detection devices., Conclusion: Despite a clear perception of the risks and a high willingness to work, preparedness is limited. The major conclusion is that basics of disaster management should be included in pediatric training.