Use of Sotrovimab in 14 Children with COVID-19: A Single-center Experience.

Children affected by coronavirus disease 2019 (COVID-19) with preexisting comorbidities are at risk of complications. Monoclonal antibodies prevent severe COVID-19 courses in adults but data on children are scarce. Here we report on the use of Sotrovimab in 14 children at risk of severe disease treated at the University of Cologne Children's Hospital. Tolerability was good and no infusion-related reactions were seen.

Impact of a pediatric infectious disease consultation service on timely step-down to oral antibiotic treatment for bone and joint infections.

PURPOSE: In recent years an earlier step down to oral antibiotic therapy has been advocated for numerous infections. Trained infectious disease specialists regularly consulting their colleagues may speed up the implementation of such recommendations into clinical practice and thus may improve treatment. METHODS: We retrospectively analyzed bone and joint infections in children admitted to the University Hospital of Cologne between 2010 and 2021. We assessed clinical, imaging, and microbiological findings and treatment modalities. Additionally, we assessed both the impact of a newly implemented pediatric infectious diseases consultation service and publications on revised treatment recommendations by comparing antibiotic therapy in two periods (2010-2016 versus 2017 to 2021). RESULTS: In total, 29 children presented with osteomyelitis, 16 with bacterial arthritis and 7 with discitis. In period 2 (2017-2021) we observed shorter duration of intravenous treatment (p = 0.009) and a higher percentage of oral antibiotic treatment in relation to the total duration of antibiotics (25% versus 59%, p = 0.007) compared to period 1 (2010-2016). Yet, no differences were identified for the total length of antibiotic treatment. Additionally, biopsies or synovial fluid samples were retrieved and cultured in more children in period 2 (p = 0.077). The main pathogen identified in osteomyelitis and bacterial arthritis was Staphylococcus aureus (MSSA), diagnosis was confirmed predominantly with MRI. CONCLUSION: Recent guidelines addressing the safety of an earlier step-down (to oral) antibiotic therapy have influenced clinical practice in the treatment of bone and joint infections in our hospital. A newly implemented pediatric infectious diseases consultation service might have accelerated this progress resulting in a faster step down to oral treatment.

What Do We Know about Spondylodiscitis in Children? A Retrospective Study.

Pediatric spondylodiscitis (PSD) is a rare disease with a major impact on mobility and functional status. Data concerning demographic and microbiological characteristics, clinical course, treatment, and outcome are scarce. Therefore, the aim of this study was to present clinical experiences of a third-level hospital (2009-2019) in PSD and compare these with adult spondylodiscitis (ASD). Of a total of 10 PSD patients, most of the infants presented with unspecific pain such as hip pain or a limping, misleading an adequate diagnosis of spine origin. Eight patients could be treated conservatively whereas surgery was performed in two cases with one case of tuberculous PSD (tPSD). The causative agent was detected in three of the patients. The diagnosis of PSD is often difficult since clinical symptoms are unspecific and causative pathogens often remain undetected. Nevertheless, empirical anti-infective therapy also seems to be effective. Based on recent studies, clinicians should be encouraged to keep the duration of anti-infective therapy in children short. Since comorbidities are not presented in PSD it is unclear which children suffer from PSD; thus, studies are necessary to identify predisposing factors for PSD. In our study, PSD differs from ASD in diagnostic and especially in therapeutic aspects. Therefore, specific guidelines for PSD would be desirable.

Drug-drug interactions in Neonatal Intensive Care Units: how to overcome a challenge.

INTRODUCTION: Critically ill patients in neonatal intensive-care units (NICU) are exposed to a large number of drugs. Clinical trials for safety, dosing and efficacy are lacking although age-dependent alterations of pharmacokinetics (PK), drug-drug-interactions (DDIs), as well as intravenous admixture incompatibilities (IAI) may impact drug efficacy and trigger side-effects in this vulnerable population. Consequently, implementation of a routinely used DDIs checking regimen may help guide in decision making and will assist clinicians to avoid serious and preventable events. Therefore, the goal of the present work is to identify and assess the risk of relevant DDIs of drugs commonly used in the NICU. EVIDENCE ACQUISITION: A literature review study was performed to identify and further assess the risk of relevant DDIs of 48 drugs frequently used in the tertiary care NICU of the University Hospital of Cologne. DDIs were categorized into five different classes according to their severity (contraindicated, minor, moderate, and major DDI, IAI), based on the classification used in the Micromedex database. In the database a major interaction is defined as any interaction that can be life threatening and/or demands medical intervention to avoid severe adverse effects. Moderate interactions can lead to a degradation of the patient's status and demand an adjustment in the therapy, and minor interactions only have a limited clinical effect. All identified DDIs in the present study are presented as a Visual Interaction Triangle (VIT) and recommendations on the management of clinically significant DDIs are provided. EVIDENCE SYNTHESIS: According to the classification used in the Micromedex database: a total of 160 (13.2%) possible interactions (DDI, IAI) were found. Fifty-five (4.9%) cases were categorized as serious interactions (DDI-major), 48 (4.2%) were less severe (DDI-moderate/minor) and in 52 (4.6%) cases an intravenous admixture drug interaction was found. Five (0.4%) drug-combinations were contraindicated. CONCLUSIONS: In this web-based study, a total of 160 DDIs were identified. Although only 4.9% were classified as clinically relevant, practitioners can use the presented VIT as a unique clinical reference to avoid possible predictable adverse effects and to uncover possible drug-interaction potential.

Running Exercise in Obese Pregnancies Prevents IL-6 Trans-signaling in Male Offspring.

PURPOSE: Maternal obesity is known to predispose the offspring to impaired glucose metabolism and obesity associated with low-grade inflammation and hypothalamic dysfunction. Because preventive approaches in this context are missing to date, we aimed to identify molecular mechanisms in the offspring that are affected by maternal exercise during pregnancy. METHODS: Diet-induced obese mouse dams were divided into a sedentary obese (high-fat diet [HFD]) group and an obese intervention (HFD-running intervention [RUN]) group, which performed voluntary wheel running throughout gestation. Male offspring were compared with the offspring of a sedentary lean control group at postnatal day 21. RESULTS: HFD and HFD-RUN offspring showed increased body weight and white adipose tissue mass. Glucose tolerance testing showed mild impairment only in HFD offspring. Serum interleukin-6 (IL-6) levels, hypothalamic and white adipose tissue IL-6 gene expressions, and phosphorylation of signal transducer and activator of transcription 3 in HFD offspring were significantly increased, whereas HFD-RUN was protected against these changes. The altered hypothalamic global gene expression in HFD offspring showed partial normalization in HFD-RUN offspring, especially with respect to IL-6 action. CONCLUSION: Maternal exercise in obese pregnancies effectively reduces IL-6 trans-signaling and might be the underlying mechanism for the amelioration of glucose metabolism at postnatal day 21 independent of body composition.

High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma.

PURPOSE: Genomic alterations of the anaplastic lymphoma kinase (ALK) gene have been postulated to contribute to neuroblastoma pathogenesis. This study aimed to determine the interrelation of ALK mutations, ALK expression levels, and clinical phenotype in primary neuroblastoma. EXPERIMENTAL DESIGN: The genomic ALK status and global gene expression patterns were examined in 263 primary neuroblastomas. Allele-specific ALK expression was determined by cDNA cloning and sequencing. Associations of genomic ALK alterations and ALK expression levels with clinical phenotypes and transcriptomic profiles were compared. RESULTS: Nonsynonymous point mutations of ALK were detected in 21 of 263 neuroblastomas (8%). Tumors with ALK mutations exhibited about 2-fold elevated median ALK mRNA levels in comparison with tumors with wild-type (WT) ALK. Unexpectedly, the WT allele was preferentially expressed in 12 of 21 mutated tumors. Whereas survival of patients with ALK mutated tumors was significantly worse as compared with the entire cohort of WT ALK patients, it was similarly poor in patients with WT ALK tumors in which ALK expression was as high as in ALK mutated neuroblastomas. Global gene expression patterns of tumors with ALK mutations or with high-level WT ALK expression were highly similar, and suggested that ALK may be involved in cellular proliferation in primary neuroblastoma. CONCLUSIONS: Primary neuroblastomas with mutated ALK exhibit high ALK expression levels and strongly resemble neuroblastomas with elevated WT ALK expression levels in both their clinical and molecular phenotypes. These data suggest that high levels of mutated and WT ALK mediate similar molecular functions that may contribute to a malignant phenotype in primary neuroblastoma.