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Aim: Non-tuberculous mycobacteria (NTM) lymphadenitis typically resolves spontaneously, yet factors influencing the duration remain explored. We aimed to identify clinical parameters associated with shorter spontaneous resolution., Methods: This cohort study included children with NTM lymphadenitis from 1 January 2015 to 1 March 2021 at Copenhagen University Hospital. Time-to-event analysis assessed clinical parameters associated with the duration of NTM lymphadenitis., Results: Sixty children (57% boys) with a median age of 24 months (range 11-84) were included; 13 (22%) received primary surgery, 13 (22%) underwent surgery after a wait-and-see period and 34 (57%) received no intervention. In children without intervention, the median duration was 10 months (range 2-25). Faster resolution was associated with parental-reported lymph node enlargement within 2 weeks (HR 2.3, 95% CI 1.0-5.0; p = 0.044), abscess on ultrasound examination (HR 3.3, 95% CI 1.5-7.3; p = 0.003) and skin discoloration and/or perforation within 3 months of onset (HR 4.3, 95% CI 1.3-14.4; p = 0.017 and HR 3.7, 95% CI 1.5-9.1; p = 0.005)., Conclusion: Knowledge of predictors for shorter spontaneous resolution of NTM lymphadenitis, such as rapid initial lymph node enlargement, abscess on ultrasound examination, and skin discoloration and/or perforation within 3 months of disease onset, may guide clinical management decisions concerning surgery versus a conservative approach., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs., Methods: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325., Findings: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, p non-inferiority =0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups., Interpretation: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship., Funding: Innovation Fund Denmark and Rigshospitalets Forskningsfond., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: Central venous saturation (ScvO2) can guide resuscitation of children with septic shock. The normal range of ScvO2 is typically considered as 0.70-0.80, but has not been established in children with cancer. Children with cancer are particularly prone to develop sepsis due to their immunosuppressive therapy, and usually have a permanent central venous catheter, making ScvO2 readily available. We aimed to investigate normal values of ScvO2 in clinically stable children with cancer, and the association between ScvO2, hemoglobin, and lactate., Methods: We conducted a prospective clinical study at the outpatient clinic of a tertiary pediatric hematology/oncology unit. Blood samples were collected from stable children aged 0-17.9 years who were treated for cancer between January 1 and November 30, 2019, during their routine outpatient clinic visits., Results: A total of 183 blood samples were collected from 68 patients (24 girls and 44 boys). The predicted mean level of ScvO2 with a 95% confidence interval was 0.67 (0.56-0.78). The ScvO2 value was below the expected lower normal limit of 0.70 in 126 (69%) of the samples and in 48 patients (71%) at least once. ScvO2 was significantly associated with hemoglobin (β1 = 0.012 per g/L hemoglobin, P < 0.001), but not with age, sex, underlying diagnosis, or lactate., Conclusions: The study revealed that a substantial portion of clinically stable childhood cancer patients exhibited ScvO2 levels below the typical reference value of 0.70, suggesting that these children may have inherently lower baseline ScvO2 levels. This should be kept in mind when evaluating children with cancer for septic shock, emphasizing the importance of tailored assessments in this population. Further understanding of baseline ScvO2 abnormalities may be helpful if ScvO2 is used to guide resuscitation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

During construction work (2017-2019), an increase in Aspergillus flavus infections was noted among pediatric patients, the majority of whom were receiving amphotericin B prophylaxis. Microsatellite genotyping was used to characterize the outbreak. A total of 153 A . flavus isolates of clinical and environmental origin were included. Clinical isolates included 140 from 119 patients. Eight patients were outbreak-related patients, whereas 111 were outbreak-unrelated patients from Danish hospitals (1994-2023). We further included four control strains. Nine A. flavus isolates were from subsequent air sampling in the outbreak ward (2022-2023). Typing followed Rudramurthy et al.(S. M. Rudramurthy, H. A. de Valk, A. Chakrabarti, J. Meis, and C. H. W. Klaassen, PLoS One 6:e16086, 2011, https://doi.org/10.1371/journal.pone.0016086). Minimum spanning tree (MST) and discriminant analysis of principal components (DAPC) were used for cluster analysis. DAPC analysis placed all 153 isolates in five clusters. Microsatellite marker pattern was clearly distinct for one cluster compared to the others. The same cluster was observed in an MST. This cluster included all outbreak isolates, air-sample isolates, and additional patient isolates from the outbreak hospital, previously undisclosed as outbreak related. The highest air prevalence of A. flavus was found in two technical risers of the outbreak ward, which were then sealed. Follow-up air samples were negative for A. flavus . Microsatellite typing defined the outbreak as nosocomial and facilitated the identification of an in-hospital source. Six months of follow-up air sampling was without A. flavus . Outbreak-related/non-related isolates were easily distinguished with DAPC and MST, as the outbreak clone's distinct marker pattern was delineated in both statistical analyses. Thus, it could be a variant of A. flavus , with a niche ability to thrive in the outbreak-hospital environment., Importance: Aspergillus flavus can cause severe infections and hospital outbreaks in immunocompromised individuals. Although lack of isogeneity does not preclude an outbreak, our study underlines the value of microsatellite genotyping in the setting of potential A. flavus outbreaks. Microsatellite genotyping documented an isogenic hospital outbreak with an internal source. This provided the "smoking gun" that prompted the rapid allocation of resources for thorough environmental sampling, the results of which guided immediate and relevant cleaning and source control measures. Consequently, we advise that vulnerable patients should be protected from exposure and that genotyping be included early in potential A. flavus outbreak investigations. Inspection and sampling are recommended at any site where airborne spores might disperse from. This includes rarely accessed areas where air communication to the hospital ward cannot be disregarded., Competing Interests: The authors declare no conflict of interest.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis., (© 2024. The Author(s).)

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.