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Persistent chylothorax is a major challenge in paediatric patients. We present a case of a 6.5 kg, 1-year-old boy with superior vena cava syndrome and persistent chylothorax who underwent successful surgery without cardiopulmonary bypass. His medical history included multiple comorbidities such as myeloproliferative disease, short bowel syndrome and central vein catheterizations. The patient also had innominate vein thrombosis, progressing to superior vena cava, and was on anticoagulants. Despite dietary changes and somatostatin, his high-output chylous pleural effusion persisted. He was treated with innominate vein-to-right atrial bypass using a 6-mm Dacron graft. Postoperatively, there was a significant reduction in effusion and accelerated recovery. Somatostatin failure was likely due to mechanical obstruction of the thoracic duct., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

This study describes ceftazidime-avibactam use in 17 young children from a resource-constrained country, where intra-abdominal infection was common. All-cause mortality was 53%. Earlier initiation, dose optimization, recording infusion times, and reviewing the need for additional antibiotics were identified as easy-to-implement-antimicrobial-stewardship interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Postpartum care focuses on prevention of health problems by performing medical check-ups and through enhancing maternal empowerment, the parent-infant interaction and knowledge about mother's own health and that of her newborn. We aimed to investigate whether there was significant clustering within neighbourhoods regarding the uptake of postpartum care and to what extent neighbourhood-level differences are explained by individual socio-demographic factors, pregnancy-related factors and neighbourhood-level determinants (i.e. deprivation and urbanization)., Methods: A nationwide population-based observational study was carried out using linked routinely collected healthcare data from appropriate-for-gestational-age weight live-born term singleton deliveries (2015-18) in the Netherlands. We performed two-level multivariable logistic regression analyses, using three different models. Model 1 contained no explanatory variables and was used to assess clustering of postpartum care uptake within neighbourhoods. In model 2, individual-level determinants were added one by one and in model 3, neighbourhood-level determinants were added., Results: About 520 818 births were included. Multilevel modelling showed that 11% of the total variance in postpartum care uptake could be attributed to the neighbourhood of residence. Individual characteristics explained 38% of the neighbourhood variance, of which income and migration background were the most important contributors. An additional 6% of the variation could be explained by neighbourhood-level determinants., Conclusion: We found substantial neighbourhood differences in postpartum care uptake. These differences are influenced by a complex interplay between individual-level and neighbourhood-level determinants, highlighting the importance of addressing both individual and neighbourhood-level determinants to improve the uptake of postpartum care and therewith overall community health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objectives: The aim of this study was to assess the early outcomes and risk factors of paediatric patients requiring extracorporeal membrane oxygenation after cardiac surgery (post-cardiotomy)., Methods: Retrospective binational cohort study from the Australia and New Zealand Congenital Outcomes Registry for Surgery database. All patients younger than 18 years of age who underwent a paediatric cardiac surgical procedure from 1 January 2013 to 31 December 2021 and required post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) in the same hospital admission were included in the study., Results: Of the 12 290 patients included in the study, 376 patients required post-cardiotomy ECMO (3%). Amongst these patients, hospital mortality was 35.6% and two-thirds of patients experienced a major complication. Hypoplastic left heart syndrome was the most common diagnosis (17%). The Norwood procedure and modified Blalock-Taussig shunts had the highest incidence of requiring PC-ECMO (odds ratio of 10 and 6.8 respectively). Predictors of hospital mortality after PC-ECMO included single-ventricle physiology, intracranial haemorrhage and chylothorax., Conclusions: In the current era, one-third of patients who required PC-ECMO after paediatric cardiac surgery in Australia and New Zealand did not survive to hospital discharge. The Norwood procedure and isolated modified Blalock-Taussig shunt had the highest incidence of requiring PC-ECMO. Patients undergoing the Norwood procedure had the highest mortality (48%). Two-thirds of patients on PC-ECMO developed a major complication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Sexuality is an integral part of human health, and sexual dysfunctions are prevalent issues that affect men and women. While reviews on sexual dysfunctions in various diseases have been conducted, overall data are scarce., Objectives: To update the overall prevalence of sexual dysfunctions from available prevalence studies on both sexes., Methods: We used a 2-phase selection process to include cross-sectional studies that were conducted on the adult population and published between 2017 and 2022. The extracted data were prevalence, methodology, sample size, and location. Sensitivity and subgroup analyses were conducted to assess heterogeneity., Results: This review analyzed 4407 studies. Twenty-three met the established criteria: 9 on the male population and 14 on the female population. The meta-analysis included 7 articles on males and 13 on females. The prevalence of sexual dysfunction was 31% in men and 41% in women, with significant heterogeneity among the studies. Sociocultural differences and use of varying measurement methods were identified as the main factors contributing to heterogeneity. Subgroup analysis revealed decreased heterogeneity among studies that used the Female Sexual Function Index as a diagnostic tool for females., Conclusions: The review highlights the notable variability in results due to methodological and geographic variations. Therefore, enhancing the training of professionals and standardizing the recording of patient data-through the Female Sexual Function Index and Male Sexual Health Questionnaire or by developing new ones for this purpose-could improve the consistency of research on sexual health., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children <5 years of age. Monocytes, especially in the respiratory tract, are suggested to contribute to RSV pathology, but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection., Methods: Tracheobronchial aspirates and blood samples were collected from control patients (n = 9) and those infected with RSV (n = 14) who were admitted to the pediatric intensive care unit. Monocytes (CD14+) were sorted and analyzed by RNA sequencing for transcriptomic profiling., Results: Peripheral blood and airway monocytes of patients with RSV demonstrated increased expression of antiviral and interferon-responsive genes as compared with controls. Cytokine signaling showed a shared response between blood and airway monocytes while displaying responses that were more pronounced according to the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation., Conclusions: We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unraveling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease., Competing Interests: Potential conflicts of interest. L. J. B. has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. The University Medical Center Utrecht (UMCU) has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill and Melinda Gates Foundation. UMCU has received major funding as part of the public-private partnership Innovative Medicines Initiative–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 MedImmune and Pfizer. UMCU received minor funding (€1000–25 000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, and Janssen. L. J. B. is the founding chair of the ReSViNET Foundation. J. G. W. has been an investigator for clinical trials sponsored by pharmaceutical companies, including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen. All funds have been paid to UMCU. J. G. W. participated in the advisory board of Janssen and Sanofi with fees paid to UMCU. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Low birthweight (bw) and unfavorable intrauterine conditions have been associated with metabolic sequelae in later life, but little is known about their impact on glucocorticoid metabolism., Objective: We studied monozygotic twins with intratwin bw differences to analyze the long-term impact of bw on glucocorticoid metabolism., Methods: 46 monozygotic twin pairs with bw differences of <1 SDS (concordant; n = 29) and ≥1 SDS (discordant; n = 17) were recruited. At 6.9 years (mean age), saliva samples were collected (at 7 hours, 13 hours, 18 hours and 21 hour) and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: We found significant or highly significant intratwin correlations in all twin pairs at 3 of 4 (cortisol), and 4 of 4 (cortisone) time points. Graphic evaluation of the diurnal cortisol patterns for each twin pair showed a distinct alignment in all groups. Analyses of the change of intratwin differences over the day by mixed linear modeling showed no intratwin differences in diurnal patterns. Regression analyses of intratwin differences at 7:00 hours showed a significant influence of catch-up growth, indicating lower cortisol concentrations in smaller twins with more catch-up growth (adj. R2 = 0.159, P = .014, ß = -3.71, F(1,42) = 9.15, f2 = 0.19)., Conclusion: In monozygotic twins with intratwin bw differences, intratwin catch-up growth showed a moderate influence on intratwin differences in morning cortisol concentrations. We observed no differences regarding diurnal patterns. In contrast, in all groups, we found significant intratwin correlations for cortisol and cortisone over the day and a pronounced graphic alignment of cortisol diurnal patterns. We therefore suggest a predominant significance of the genetic background compared with bw differences on cortisol metabolism., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Overweight and obesity in children with congenital heart disease (CHD) represent an alarming cardiovascular risk. Promotion of physical activity and cardiac rehabilitation in this population requires assessing the level of aerobic fitness (VO2max) by a cardiopulmonary exercise test (CPET). Nevertheless, the interpretation of CPET in overweight/obese children with CHD remains challenging as VO2max is affected by both the cardiac condition and the body mass index (BMI). The new paediatric VO2max  Z-score reference equations, based on a logarithmic function of VO2max, height and BMI, were applied to overweight/obese children with a CHD and compared with overweight/obese children without any other chronic condition., Methods and Results: In this cross-sectional controlled study, 344 children with a BMI > 85th percentile underwent a CPET (54% boys; mean age 11.5 ± 3.1 years; 100 CHD; 244 controls). Using the VO2max  Z-score equations, aerobic fitness was significantly lower in obese/overweight CHD children than that in matched obese/overweight control children (-0.43 ± 1.27 vs. -0.01 ± 1.09; P = 0.02, respectively), and the proportion of children with impaired aerobic fitness was significantly more important in obese/overweight CHD children than in matched controls (17% vs.6%, P = 0.02, respectively). The paediatric VO2max  Z-score reference equations also identified specific complex CHD at risk of aerobic fitness impairment (univentricular heart and right outflow tract anomalies). Using Cooper's weight- and height-based linear equations, similar matched-comparisons analyses found no significant group differences., Conclusions: As opposed to the existing linear models, the new paediatric VO2max  Z-score equations can discriminate the aerobic fitness of obese/overweight children with CHD from that of obese/overweight children without any chronic disease., Registration: ClinicalTrials.gov NCT04815577., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest: the authors declare they have no conflicts of interest.

Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections., Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39)., Results: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV., Conclusions: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Little is known about the risk of multisystem inflammatory syndrome in children (MIS-C) with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in children aged 0-16 years were 56% lower (rate ratio [RR], 0.34 [95% confidence interval {CI}, .23-.50]) during prevaccine Delta, 66% lower (RR, 0.44 [95% CI, .28-.69]) during postvaccine Delta, and 95% lower (RR, 0.05 [95% CI, .02-.10]) during the Omicron period., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The Berlin Heart EXCOR (BHE) offers circulatory support across all paediatric ages. Clinically, the necessary care and the outcomes differ in various age groups. The EUROMACS database was used to study age- and size-related outcomes for this specific device., Methods: All patients <19 years of age from the EUROMACS database supported with a BHE between 2000 and November 2021 were included. Maximally selected rank statistics were used to determine body surface area (BSA) cut-off values. Multivariable Cox proportional hazard regression using ridge penalization was performed to identify factors associated with outcomes., Results: In total, 303 patients were included [mean age: 2.0 years (interquartile range: 0.6-8.0, males: 48.5%)]. Age and BSA were not significantly associated with mortality (n = 74, P = 0.684, P = 0.679). Factors associated with a transplant (n = 175) were age (hazard ratio 1.07, P = 0.006) and aetiology other than congenital heart disease (hazard ratio 1.46, P = 0.020). Recovery rates (n = 42) were highest in patients with a BSA of <0.53 m2 (21.8% vs 4.3-7.6% at 1 year, P = 0.00534). Patients with a BSA of ≥0.73 m2 had a lower risk of early pump thrombosis but a higher risk of early bleeding compared to children with a BSA of <0.73 m2., Conclusions: Mortality rates in Berlin Heart-supported patients cannot be predicted by age or BSA. Recovery rates are remarkably high in the smallest patient category (BSA <0.53 m2). This underscores that the BHE is a viable therapeutic option, even for the smallest and youngest patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Cardiac surgery with hypothermic circulatory arrest (HCA) is associated with neurological morbidity of variable severity and electroencephalography (EEG) is a sensitive proxy measure of brain injury. We conducted a narrative review of the literature to evaluate the role of perioperative EEG monitoring in cardiac surgery involving HCA., Methods: Medline, Embase, Central and LILACS databases were searched to identify studies utilizing perioperative EEG during surgery with HCA in all age groups, published since 1985 in any language. We aimed to compare EEG use with no use but due to the lack of comparative studies, we performed a narrative review of its utility. Two or more reviewers independently screened studies for eligibility and extracted data., Results: Fourty single-centre studies with a total of 3287 patients undergoing surgery were identified. Most were observational cohort studies (34, 85%) with only 1 directly comparing EEG use with no use. EEG continuity (18, 45%), seizures (15, 38%) and electrocerebral inactivity prior to circulatory arrest (15, 38%) were used to detect, monitor, prevent and prognose neurological injury. Neurological dysfunction was reported in almost all studies and occurred in 0-21% of patients. However, the heterogeneity of reported clinical and EEG outcome measures prevented meta-analysis., Conclusions: EEG is used to detect cortical ischaemia and seizures and predict neurological abnormalities and may guide intraoperative cerebral protection. However, there is a lack of comparative data demonstrating the benefit of perioperative EEG monitoring. Use of a standardized methodology for performing EEG and reporting outcome metrics would facilitate the conduct of high-quality clinical trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also sought to evaluate the use of capillary microsampling to facilitate data-rich blood sampling., Methods: Patients were recruited into a pharmacokinetic study, with cefotaxime and desacetylcefotaxime concentrations from plasma samples collected at 0, 0.5, 2, 4 and 6 h used to develop a population pharmacokinetic model using Pmetrics. Monte Carlo dosing simulations were tested using a range of estimated glomerular filtration rates (60, 100, 170 and 200 mL/min/1.73 m2) and body weights (4, 10, 15, 20 and 40 kg) to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets, including 100% ƒT>MIC with an MIC breakpoint of 1 mg/L., Results: Thirty-six patients (0.2-12 years) provided 160 conventional samples for inclusion in the model. The pharmacokinetics of cefotaxime and desacetylcefotaxime were best described using one-compartmental model with first-order elimination. The clearance and volume of distribution for cefotaxime were 12.8 L/h and 39.4 L, respectively. The clearance for desacetylcefotaxime was 10.5 L/h. Standard dosing of 50 mg/kg q6h was only able to achieve the PK/PD target of 100% ƒT>MIC in patients >10 kg and with impaired renal function or patients of 40 kg with normal renal function., Conclusions: Dosing recommendations support the use of extended or continuous infusion to achieve cefotaxime exposure suitable for bacterial killing in critically ill paediatric patients, including those with severe or deep-seated infection. An external validation of capillary microsampling demonstrated skin-prick sampling can facilitate data-rich pharmacokinetic studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Motivation: Sepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking., Results: This study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care., Availability and Implementation: Code available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

Objectives: Our goal was to describe postoperative complications and outcomes in a large contemporary cohort of children with an isolated double aortic arch (DAA) or a right aortic arch (RAA) with left arterial ligament and to assess the impact of foetal diagnosis on outcomes., Methods: We performed a retrospective analysis of all patients who underwent surgery for DAA or RAA with left arterial ligament between 2005 and 2019., Results: A total of 132 children were operated on for a DAA (n = 77) or a RAA (n = 55). Prenatal diagnosis was made in 100/132 (75.8%). Median age at surgery for DAA was 5.0 (1.7-13.3) months and for RAA was 13.9 (6.4-20.1) months. There was no difference in the age at surgery between the prenatal and postnatal cases (8.6 [4.0-15.6] vs 5.4 months [1.8-17.7]; P = 0.37). No surgical deaths occurred. Vocal cord palsy was the most common complication, occurring in 12/132 (9%): of these, 11 resolved spontaneously and 1 required a temporary tracheostomy. Logistic regression demonstrated that older age at operation was the only predictor for a postoperative complication (P = 0.02). Overall, 21/67 (31%) of prenatally detected, symptomatic cases reported residual symptoms/signs 1 year after surgery compared to 18/28 (64%) of postnatally detected cases. Postnatal diagnosis was associated with persistent postoperative symptoms/signs [P = 0.006, odds ratio = 3.9 (95% confidence interval 1.5-9.4)]., Conclusions: Surgery to relieve a vascular ring resolves trache-oesophageal compressive symptoms in most cases, but parents/patients should be aware that symptoms/signs may persist in the first postoperative year despite effective release of the vascular ring. Earlier surgery and prenatal diagnosis may improve outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Cardiopulmonary bypass generates a systemic inflammatory response. This inflammatory response is reduced if patients are ventilated during bypass, as evidenced by lower levels of postoperative circulating inflammatory mediators. However, this does not appear to make much clinical difference in adults, at least not consistently, but, to our knowledge, has never been assessed in paediatric cardiac surgery, which is the objective of this study., Methods: This is a prospective clinical study of 12 consecutive neonates operated for the correction of either transposition of the great arteries ± ventricular septal defect or aortic arch hypoplasia ± ventricular septal defect, who were ventilated during cardiopulmonary bypass. These were compared to 11 neonates with the same malformations, who had undergone the same operations but without being ventilated during bypass (historical control group)., Results: One patient from the control group died on the 15th postoperative day due to sepsis and multi-organ failure. Bypass times and cross-clamp times were similar in the 2 groups. Ventilation on bypass was associated with significantly lower postoperative serum concentrations of C-reactive protein, shorter mechanical ventilation and lower vasoactive-inotropic score. Duration of stay on intensive care unit (ICU) showed a tendency to be shorter in patients who were ventilated on bypass, but this did not reach statistical significance. There were no differences between the 2 groups with respect to postoperative mixed venous oxygen saturations and serum concentrations of lactate and troponin I., Conclusions: Mechanical ventilation during cardiopulmonary bypass in neonates improves postoperative outcome., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Mesenchymal stromal cells (MSCs) are widely used in preclinical and clinical research. Despite minimal criteria to define MSCs provided by the International Society for Cell and Gene Therapy (ISCT), concerns have been raised about inconsistent descriptions of cell products used. To address the question "How are MSCs currently defined and characterized?" we conducted a scoping review on original MSC preclinical and clinical studies published over a 3-month period. Selected studies identified from a systematic search of MEDLINE and Embase were categorized as follows: Clinical, Animal, Biology, or Biomaterial studies. Data were extracted from a randomly selected subsample of studies. We extracted information, including epidemiological characteristics of studies, study design, ISCT criteria, and MSC characterization and culture condition. A total of 1053 articles were included and among them, 318 articles were analyzed. Overall, 18% of the articles explicitly referred to the ISCT minimal criteria for MSC. MSC characteristics and culture conditions were inconstantly reported (eg, viability assay reported in only 18% of the articles). Only 20% of documents reported at least 1 functional assay. Clinical studies showed inconsistent completeness in reporting relevant information on the MSC characterization and cell manufacturing processes. These results suggest that further development and implementation of a consensus definition of MSCs and reporting guidelines are needed to enhance rigor, reproducibility, and transparency in MSC research., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools., Methods: During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2-5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated., Results: Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5-10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9., Conclusions: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD)., Methods: We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature., Results: KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients., Conclusion: On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful., Methods: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis)., Results: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis., Conclusions: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A 7-year-old Liberian boy presented with fever, severe headache, neck pain and 'not being able to walk'. In the emergency room, his sickle cell screen was positive, and his haemoglobin level was 7 g/dl. Initially, he was admitted to the ward with a diagnosis of sickle cell painful crisis and was treated with ceftrixone iv, and oral morphine and paracetamol. In a more complete physical examination, he had left peripheral seventh nerve palsy, left sixth nerve palsy and ipsilateral hemiplegia, also neck rigidity. In a bedside ultrasound scan, he had a large, mobile vegetation on the aortic leaflet of the mitral valve. The final diagnosis was acute infective endocarditis with multiple embolic strokes in a child with sickle cell disease. Headache and neck rigidity was most likely due to SAH or meningitis., (© The Author(s) [2021]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Down syndrome (DS) predisposes to severe immunologic reaction secondary to infectious triggers. Here, we report a pediatric DS patient with coronavirus disease 2019 (COVID-19) who developed a hyperinflammatory syndrome, severe acute respiratory distress syndrome, and secondary hemophagocytic lymphohistiocytosis requiring pediatric intensive care unit admission and treatment with steroids, intravenous immunoglobulin, and remdesivir. Investigations into genetic susceptibilities for COVID-19 and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated complications warrant systematic clinical and scientific studies. We report a pediatric Down syndrome patient with coronavirus disease 2019 (COVID-19) who developed secondary hemophagocytic lymphohistiocytosis requiring treatment with steroids, intravenous immunoglobulin, and remdesivir. Investigations into genetic susceptibilities for COVID-19-associated complications warrant systematic clinical and scientific studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is significant variability in the names and case definition of pediatric inflammatory multisystem syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Such variability leads to adverse consequences in the quest for further knowledge and management strategies. It is time to collaborate to gain consensus., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging., Objectives: To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management., Methods: We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data., Results: A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion., Conclusions: Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience., (© 2020 British Association of Dermatologists.)

Diagnostic accuracy studies are fundamental for the assessment of diagnostic tests. Researchers need to understand the implications of their chosen design, opting for comparative designs where possible. Researchers should analyse test accuracy studies using the appropriate methods, acknowledging the uncertainty of results and avoiding overstating conclusions and ignoring the clinical situation which should inform the trade-off between sensitivity and specificity. Test accuracy studies should be reported with transparency using the STAndards for the Reporting of Diagnostic accuracy studies (STARD) checklist.

Introduction: Children usually present with minimal or no symptoms of COVID-19 infection. Antibody responses to SARS-CoV-2 in children from low- and middle-income countries (LMIC) have not been well described. We describe the prevalence of anti-SARS-CoV-2 antibodies and clinical phenotype of seropositive children admitted to a tertiary children's hospital in South India., Methods: To determine the seropositivity and describe the clinical characteristics of COVID-19 infection amongst hospitalised children, we performed a prospective clinical data collection and blood sampling of children admitted to Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India over 4 months of the COVID-19 pandemic. In seropositive children, we compared antibody titres between children with and without PIMS-TS., Results: Of 463 children, 91 (19.6%) were seropositive. The median (range) age of seropositive children was 5 years (1 month-17 years). Clinical presentation was consistent with Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) in 48% (44/91) of seropositive children. The median (range) antibody titre was 54.8 (11.1-170.9) AU/ml among all seropositive children. The median antibody titre among the children with PIMS-TS (60.3 AU/mL) was significantly (p = 0.01) higher when compared to the children without PIMS-TS (54.8 AU/mL)., Conclusion: We describe the antibody responses to SARS-CoV-2 amongst hospitalised children in a LMIC tertiary children's hospital. Almost half of the seropositive children had PIMS-TS. Antibody levels may be helpful in the diagnosis and disease stratification of PIMS-TS., Lay Summary: Children usually present with minimal or no symptoms of COVID-19 infection. However, Multisystem Inflammatory Syndrome in Children (MIS-C) or Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) has emerged as a distinctive paediatric illness related to SARS-CoV-2. Recently, antibody testing for SARS-CoV-2 is being used increasingly as a diagnostic test for PIMS-TS. However, data on the antibody responses to SARS-CoV-2 in children are sparse. We, therefore, attempted to identify the seropositivity and describe the clinical spectrum of COVID-19 infection amongst infants and children getting hospitalised in a children's hospital in south India. Nearly one-fifth of the hospitalised children tested serology positive over 4 months. Antibody levels in children with PIMS-TS were significantly higher in comparison to the other two groups (acute COVID-19 infection and children without PIMS-TS). Results from our study suggest that all children are at risk of COVID-19 infection though they may present with mild illness or no symptoms. We also observed that antibody testing may have a possible role in diagnosis of PIMS-TS., (© The Author(s) [2021]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI)., Objectives: To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort., Methods: A retrospective observational single-centre study (December 2005-August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed., Results: Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival., Conclusions: CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes., Methods: We conducted a multicenter, population-based, prospective study including previously healthy children aged ≥28 days and <17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported., Results: There were 176 children presenting with 185 sepsis episodes who underwent WES (median age, 52 months; interquartile range, 15.4-126.4). There were 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants that were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories, as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants., Conclusions: Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected variants of uncertain significance in PID genes in 1 out of 5 children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: An estimated 3.2 million patients annually develop healthcare-associated infections (HCAIs) in Europe alone amid the major challenge of increasing antimicrobial resistance. Critically ill children warrant specific evaluation because of differences in epidemiology, causative organisms and infection sites., Objectives: To examine the prevalence and antimicrobial susceptibility patterns of three types of HCAI in critically ill children and determine the effect on their disease course., Materials and Methods: Retrospective cohort review of critically ill children admitted to a general paediatric ICU (PICU) at a regional academic tertiary referral centre over a 3 year period., Results: There were 1930 admissions with a median age of 38 months. Children with HCAIs had a higher incidence of comorbidities (74% versus 24%) and a longer median length of stay (8 days versus 3 days). We identified 26 positive isolates (blood, lower respiratory and urine) taken 48 h or more after admission. The combined incidence was 1.34%. Hospital-acquired pneumonia accounted for 58% of HCAIs, urinary tract infections for 31% and bloodstream infections for 11%. The majority (61.5%) of HCAIs were caused by Gram-negative organisms. Seven isolates were resistant to antimicrobials used to treat HCAI. All of these were Gram-negative organisms ( Pseudomonas aeruginosa , Klebsiella oxytoca and Escherichia coli )., Conclusions: These data revealed a low incidence of HCAIs, 27% of which were resistant Gram-negative organisms. Critically ill children with HCAIs were more likely to have comorbidities and an increased length of stay. These factors may increasingly impact on PICU bed availability, an already limited resource., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objectives: Patients with complex congenital heart disease carry an increased risk of damage to retrosternal structures each time they undergo redo sternotomy. The aim of this study was to evaluate the safety and efficacy of neck cannulation for peripheral cardiopulmonary bypass to alleviate the risks in high-risk redo sternotomy patients., Methods: Children and adults with congenital heart disease undergoing high-risk redo sternotomy were included in this retrospective study. The primary outcome was the safety and efficacy of neck cannulation for cardiopulmonary bypass. The secondary outcome was to assess preoperative risk factors as an indication for neck cannulation. The right common carotid artery and right internal jugular vein were cannulated and full cardiopulmonary bypass was initiated with vacuum-assisted venous drainage. Redo sternotomy was performed on a decompressed heart, and bifrontal regional cerebral oxygen saturation was monitored via near-infrared spectroscopy., Results: In total, 35 patients were included. No mortality, neurological or vascular complications occurred postoperatively. Mean left- and right-sided near-infrared spectroscopy were 70.0% (±10.5) and 64.2% (±12.0), respectively, and the mean difference was 5.7% (±6.9). Main preoperative risk factors were; adherent ascending aorta (45.7%), adherent conduit (40%), severely dilated retrosternal right ventricle (17.1%) and skeletal deformations (14.3%)., Conclusions: Cannulation of the right neck vessels for peripheral cardiopulmonary bypass prior to high-risk redo sternotomy in children and adults with congenital heart disease is a safe and effective strategy. In combination with near-infrared spectroscopy monitoring, adequate cerebral oxygenation can be ensured while the risk of catastrophic haemorrhage is minimized., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The interstage mortality rate after a Norwood stage 1 operation remains 12-20% in current series. In-hospital interstage facilitates escalation of care, possibly improving outcome., Methods: A retrospective study was designed for hypoplastic left heart syndrome (HLHS) and HLHS variants, offering an in-hospital stay after the Norwood operation until the completion of stage 2. Daily and weekly examinations were conducted systematically, including two-dimensional and speckle-tracking echocardiography. Primary end points included aggregate survival until the completion of stage 2 and interstage freedom from escalation of care. Moreover, we calculated the sensitivity and specificity of speckle-tracking echocardiographic myocardial deformation in predicting death/transplant after the Norwood procedure., Results: Between 2015 and 2019, 33 neonates with HLHS (24) or HLHS variants (9) underwent Norwood stage 1 (31) or hybrid palliation followed by a comprehensive stage 2 operation (2). Stage 1 Norwood-Sano was preferred in 18 (54.5%) neonates; the classic Norwood with Blalock-Taussig shunt was performed in 13 (39.4%) neonates. The Norwood stage 1 30-day mortality rate was 6.2%. The in-hospital interstage strategy was implemented after Norwood stage 1 with a 3.4% interstage mortality rate. The aggregate Norwood stage 1 and interstage Kaplan-Meier survival rate was 90.6 ± 5.2%. Escalation of care was necessary for 5 (17.2%) patients at 2.5 ± 1.2 months during the interstage for compromising atrial arrhythmias (2), Sano-shunt stenosis (1) and pneumonia requiring a high-frequency oscillator (2); there were no deaths. A bidirectional Glenn (25) or a comprehensive-Norwood stage 2 (2) was completed in 27 patients at 4.7 ± 1.2 months with a 92.6% survival rate. The overall Kaplan-Meier survival rate is 80.9 ± 7.0% at 4.3 years (mean 25.3 ± 15.7 months). An 8.7% Δ longitudinal strain 30 days after Norwood stage 1 had 100% sensitivity and 81% specificity for death/transplant., Conclusions: In-hospital interstage facilitates escalation of care, which seems efficacious in reducing interstage Norwood deaths. A significant reduction of longitudinal strain after Norwood stage 1 is a strong predictor of poor outcome., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Neisseria meningitidis (Nm) is a nasopharyngeal commensal carried by healthy individuals. However, invasive infections occurs in a minority of individuals, with devastating consequences. There is evidence that common polymorphisms are associated with invasive meningococcal disease (IMD), but the contributions of rare variants other than those in the complement system have not been determined., Methods: We identified familial cases of IMD in the UK meningococcal disease study and the European Union Life-Threatening Infectious Disease Study. Candidate genetic variants were identified by whole-exome sequencing of 2 patients with familial IMD. Candidate variants were further validated by in vitro assays., Results: Exomes of 2 siblings with IMD identified a novel heterozygous missense mutation in BPIFA1/SPLUNC1. Sequencing of 186 other nonfamilial cases identified another unrelated IMD patient with the same mutation. SPLUNC1 is an innate immune defense protein expressed in the nasopharyngeal epithelia; however, its role in invasive infections is unknown. In vitro assays demonstrated that recombinant SPLUNC1 protein inhibits biofilm formation by Nm, and impedes Nm adhesion and invasion of human airway cells. The dominant negative mutant recombinant SPLUNC1 (p.G22E) showed reduced antibiofilm activity, increased meningococcal adhesion, and increased invasion of cells, compared with wild-type SPLUNC1., Conclusions: A mutation in SPLUNC1 affecting mucosal attachment, biofilm formation, and invasion of mucosal epithelial cells is a new genetic cause of meningococcal disease., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: Free Open Access Meducation (FOAM) describes online resources assisting learning in medicine. Little is known about users or their behaviours., Methods: Using Google Analytics for a popular FOAM site (www.paedatricfoam.com), we explored user demographics and patterns of behaviour. We analysed these further with descriptive and statistical tests using SPSS (version 26). Data are presented as mean (SD)., Results: There were 181.44 (75.16) mean daily users accessing the site throughout a 4-month period during 2018/2019. 68.9% of users were female; 44% were 25-34 years; 57.3% used a mobile device. The mean session duration was 73.55 (9.41) seconds, with more time spent per session and a greater number of pages per session observed in users accessing the site from a desktop or tablet as opposed to a mobile phone. 84.3% of mobile users left the site after viewing a single page. Referral source was also associated with device used (p<0.001). Age was not related to user behaviours (p>0.05)., Discussion: FOAM is a rapidly developing form of medical education, with large user numbers seen for a site just 2 years old. The site is being used by many beyond its intended readership. Rather than accessing multiple pages from a desktop, users have varied online behaviours, with the majority viewing a single page on a mobile phone, referred by social media or Google., Conclusions: Google Analytics can powerfully display usage of medical websites but has important limitations if statistical exploration is required. FOAM users are a heterogenous group, and thus content should be designed with this in mind. Further research must be prioritised focussing on the scope, curriculum coverage, accuracy of information and the effectiveness of FOAM as an educational resource., Competing Interests: Competing interests: KK is the lead editor for www.paediatricfoam.com. JR is an editor for www.paediatricfoam.com., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Symptomatic neonates with Ebstein anomaly present with intractable heart failure. We present the first successful cone reconstruction in an ex 30 + 4-week premature below 2 kg with a favourable outcome., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The upcoming release of aprotinin in paediatric cardiac surgery prompted a re-evaluation of its use in comparison to tranexamic acid (TXA) focusing on their effect on exposure to blood transfusions as well as severe postoperative morbidity or mortality., Methods: This retrospective study was conducted in a tertiary children hospital from 2002 to 2015. Patients receiving aprotinin (Aprotinin group: 2002-2007) were compared with those receiving TXA group (2008-2015) using propensity score analysis. Primary outcome measures were 'exposure to blood products' and 'severe postoperative morbidity or mortality'. High-risk subgroups that included neonates, complex (Risk Adjusted Classification for Congenital Heart Surgery-1 ≥ 3) and redo surgery were also analysed., Results: The study included 2157 patients, 1136 in the Aprotinin group and 1021 in the TXA group. Exposure to blood products was significantly higher in the Aprotinin group (78% vs 60%; P < 0.001) as well as in the complex and redo surgery subgroups. Incidence of mortality and/or severe morbidity was higher in the Aprotinin group (33% vs 28%; P = 0.007), as well as in the neonate group. However, cardiopulmonary bypass priming volume and intraoperative fluid balance were significantly decreased, and the use of modified ultrafiltration significantly increased in the TXA group., Conclusions: In our population, children receiving aprotinin were more frequently transfused and were at a higher risk of developing severe postoperative morbidity or mortality than those receiving TXA. Subgroups at high risk of bleeding or inflammation did not seem to benefit from aprotinin. These differences might be explained by a safer profile of TXA, but also attributed to major changes in our patient blood management strategies over years., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study is to determine whether recombinant activated factor VII (rVIIa) was associated with thrombus formation in neonates undergoing cardiac surgery., Methods: This is a retrospective study of neonates undergoing surgical repair of congenital cardiac lesions during a 9-year period., Results: In our study, 416 cardiac operations requiring cardiopulmonary bypass (CPB) were performed on 414 neonates. The overall intravascular thrombus (thrombus) frequency for all operations was 45 of 416 (11%). A thrombus developed in 17 of 287 (6%) operations when rVIIa was not given. rVIIa was administered in 129 of 416 (31%) operations. Thrombus formation occurred in 28 of 129 (22%) operations when rVIIa was administered. There was an association between rVIIa use and thrombus formation [odds ratio (OR) 4.4, 95% confidence interval (CI) 2.3-8.4; P < 0.0001]. Patients with thrombus formation had an increased length of stay compared to those without thrombus. Neonates who underwent the Norwood procedures and received rVIIa and developed thrombus were more likely to be supported with extracorporeal membrane oxygenation (ECMO) and had a higher mortality compared to Norwood patients without thrombus. Logistic analysis adjusted for the paediatric index of mortality 2 score, the risk adjustment for congenital heart surgery and the use of ECMO demonstrated a strong association between rVIIa administration and thrombus formation (OR 3.5, 95% CI 1.7-6.9; P = 0.0004). However, there was no effect of the risk adjustment for congenital heart surgery-1 category or the paediatric index of mortality 2 score on thrombus formation., Conclusions: In neonates who underwent CPB surgery, administration of rVIIa was associated with an increased occurrence of intravascular thrombus formation compared to neonates not given rVIIa. In the Norwood population, thrombus formation was associated with a higher mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Drug resistance mutations (DRMs) increasingly jeopardize paediatric HIV programmes in sub-Saharan Africa. As individual monitoring of DRMs and viral loads has limited availability, population data on DRMs are essential to determine first-line susceptibility. Paediatric data from sub-Saharan Africa are scarce and unavailable for Malawi., Objectives: To determine the prevalence of virological failure (VF) and DRMs among ART-naive HIV-infected Malawian children during the first year of first-line ART., Methods: In a prospective cohort of HIV-infected Malawian children, on first-line treatment, children were followed monthly; blood was collected for viral load testing (6 and 12 months) and genotypic resistance testing (12 months). VF was defined as at least one viral load >1000 copies/mL or death after 6 months of ART. DRMs were identified and susceptibility to NRTIs and NNRTIs was scored using the Stanford algorithm and by calculating genotypic susceptibility scores (GSSs)., Results: VF occurred in 66% (23/35) of the children during 12 months of follow-up. DRMs were detected in 44% (15/34); all had NNRTI resistance and 12% (4/34) had dual-class NNRTI/NRTI resistance. Reduced susceptibility (DRMs and GSS <3) was seen in 41% (14/34) to their current first-line regimen. High-level resistance was most common for nevirapine [26% (9/34)]., Conclusions: In this first report on VF and DRMs in children on first-line ART in Malawi, the rates of VF and DRMs were alarmingly high. Paediatric HIV programmes in sub-Saharan Africa should emphasize programmatic evaluation of VF and include detection of DRMs to adjust and design adequate first- and second-line regimens and prevent widespread resistance in children.

Background: Blood culture results are frequently used to guide antibiotic decision-making, but culture contaminants need to be distinguished from true pathogens., Aims: To assess the contamination rate of blood cultures and validate a method to distinguish between true bacteraemia and contamination., Methods: We analysed blood culture results from children who were admitted to the paediatric ICU and paediatric wards at the Sardjito Hospital, Yogyakarta, Indonesia between December 2010 and February 2013. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to classify the isolate as representing a true bacteraemia or contaminant., Results: There were 1293 cultures obtained from blood and 308 (23.8%) were positive for bacterial growth. Fifty-three (4.1%) of the total cultures drawn fulfilled criteria for contaminants. The most common blood culture contaminants were coagulase-negative staphylococci., Conclusion: Using standardized criteria, it is possible to implement a working method to identify true nosocomial infection from blood culture contaminant, and thus limit the effect of contaminated blood culture on irrational antibiotic use.

We report a case of a 4-year-old boy from Oyo, Nigeria, presenting with prolonged seizures and coma with the subsequent development of oro-lingual-facial dyskinesia with frequent tongue thrusting, dysconjugate gaze and choreoathetoid movements of the limbs because of autoimmune encephalitis consistent with anti-N-methyl-D-aspartate (anti-NMDAR) encephalitis.

Objectives: When evaluated prospectively, acute brain injury is reported in up to 75% of neonates undergoing cardiopulmonary bypass (CPB), predominantly white matter injury rather than stroke. This study investigates the incidence of stroke (focal infarct and/or haemorrhage) detected by neuroimaging in contemporary clinical practice, whereby magnetic resonance imaging/computed tomography routinely occurs in response to clinical events, comparing those undergoing the Norwood procedure with those undergoing other neonatal procedures involving CPB, and defines the relationship between stroke and neurodevelopmental disability (NDD) at 12 months of age., Methods: One hundred and twenty neonates underwent CPB between July 2011 and December 2014: 25 Norwood procedures and 95 non-Norwood procedures. Data were retrospectively collected including clinical data and 12-month neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)., Results: Stroke was detected in 12% of neonates in current clinical practice: 24% of the Norwood group vs 8% of the non-Norwood group (P = 0.03). Significant predictors of stroke in the univariate analysis included the Norwood procedure, lowest operative temperature and use of extracorporeal membrane oxygenation (P < 0.05). The lowest operative temperature and use of extracorporeal membrane oxygenation remained significant in the multivariate analysis (P < 0.05). Fifty-seven percent were assessed using the BSID-III assessment, and 68% demonstrated NDD in at least 1 subscale. In neonates who suffered stroke, the incidence of NDD was significantly greater in 4/5 subscales compared with those with no injury (P < 0.05). The Norwood group had a significantly greater incidence of NDD in 2/5 subscales when compared with the non-Norwood group (P < 0.05)., Conclusions: Stroke, established by neuroimaging in contemporary clinical practice, was detected in 12% of neonates having CPB, and those undergoing the Norwood procedure have a 3-fold risk of injury. Stroke was associated with NDD at 12 months of age.

We studied the presence of triazole resistance of 121 Aspergillus fumigatus clinical isolates collected in two Polish cities, Warsaw and Wrocław, to determine if resistance is emerging in our country. We identified five itraconazole resistant isolates (4.13%) carrying the TR34/L98H alteration in Cyp51A gene, four of which were cross-resistant to posaconazole and one to voriconazole. One isolate was intermediate susceptible to itraconazole and harbored no Cyp51A alterations. The study confirms the presence of azole resistant A. fumigatus strains in Poland at a level that is comparative to other European countries., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)