Preadmission course and management of severe pediatric group A streptococcal infections during the 2022-2023 outbreak: a single-center experience.

PURPOSE: The massive increase of infections with Group A Streptococcus (GAS) in 2022-2023 coincided in Switzerland with a change of the recommendations for the management of GAS pharyngitis. Therefore, the objective of the present study was to investigate whether the clinical manifestations and management before hospitalization for GAS infection differed in 2022-2023 compared with 2013-2022. METHODS: Retrospective study of GAS infections requiring hospitalization in patients below 16 years. Preadmission illness (modified McIsaac score), oral antibiotic use, and outcome in 2022-2023 were compared with 2013-2022. Time series were compared with surveillance data for respiratory viruses. RESULTS: In 2022-2023, the median modified McIsaac score was lower (2 [IQR 2-3] vs. 3 [IQR 2-4], p = < 0.0001) and the duration of preadmission illness was longer (4 days [3-7] vs. 3 [2-6], p = 0.004) than in 2013-2022. In both periods, withholding of preadmission oral antibiotics despite a modified McIsaac score ≥ 3 (12% vs. 18%, n.s.) or ≥ 4 (2.4% vs. 10.0%, p = 0.027) was rare. Respiratory disease, skeletal/muscle infection, and invasive GAS disease were significantly more frequent in 2022-2023, but there were no differences in clinical outcome. The time course of GAS cases in 2022-2023 coincided with the activity of influenza A/B. CONCLUSION: We found no evidence supporting the hypothesis that the 2022-2023 GAS outbreak was associated with a change in preadmission management possibly induced by the new recommendation for GAS pharyngitis. However, clinical manifestations before admission and comparative examination of time-series strongly suggest that viral co-circulation played an important role in this outbreak.

Cytokine Signaling in Pediatric Kidney Tumor Cell Lines WT-CLS1, WT-3ab and G-401.

Renal tumors comprise ~7% of all malignant pediatric tumors. Approximately 90% of pediatric kidney tumors comprise Wilms tumors, and the remaining 10% include clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, renal cell carcinoma and other rare renal tumors. Over the last 30 years, the role of cytokines and their receptors has been considerably investigated in both cancer progression and anti-cancer therapy. However, more effective immunotherapies require the cytokine profiling of each tumor type and comprehensive understanding of tumor biology. In this study, we aimed to investigate the activation of signaling pathways in response to cytokines in three pediatric kidney tumor cell lines, in WT-CLS1 and WT-3ab cells (both are Wilms tumors), and in G-401 cells (a rhabdoid kidney tumor, formerly classified as Wilms tumor). We observed that interferon-alpha (IFN-α) and interferon-gamma (IFN-γ) very strongly induced the activation of the STAT1 protein, whereas IL-6 and IFN-α activated STAT3 and IL-4 activated STAT6 in all examined tumor cell lines. STAT protein activation was examined by flow cytometry and Western blot using phospho-specific anti-STAT antibodies which recognize only activated (phosphorylated) STAT proteins. Nuclear translocation of phospho-STAT proteins upon activation with specific cytokines was furthermore confirmed by immunofluorescence. Our results also showed that both IFN-α and IFN-γ caused upregulation of major histocompatibility complex (MHC) class I proteins, however, these cytokines did not have any effect on the expression of MHC class II proteins. We also observed that pediatric kidney tumor cell lines exhibit the functional expression of an additional cytokine signaling pathway, the tumor necrosis factor (TNF)-α-mediated activation of nuclear factor kappa B (NF-κB). In summary, our data show that human pediatric renal tumor cell lines are responsive to stimulation with various human cytokines and could be used as in vitro models for profiling cytokine signaling pathways.

Long-term pulmonary outcome of children with congenital diaphragmatic hernia: functional lung MRI using matrix-pencil decomposition enables side-specific assessment of lung function.

OBJECTIVES: In patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI. METHODS: Thirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV1), lung clearance index (LCI2.5), ventilation defect percentage (VDP), and perfusion defect percentage (QDP). RESULTS: Patients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CIadjusted]: FEV1 (z-score) -4.26 [-5.61, -2.92], FVC (z-score) -3.97 [-5.68, -2.26], LCI2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CIadjusted]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20]). CONCLUSIONS: Data indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH. CLINICAL RELEVANCE STATEMENT: In patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up. KEY POINTS: • Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH). • Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects.

[Workplace-based Assessments: A Needs Analysis of Residents and Supervisors]. / Arbeitsplatz-basierte Assessments: eine Bedarfsanalyse bei Assistenzärztinnen und ­ärzten sowie ihren Supervisierenden.

Workplace-based Assessments: A Needs Analysis of Residents and Supervisors Abstract. During residency training, four workplace-based assessments (WBA) are planned per year in the form of Mini-CEX and/or DOPS. They were introduced as a tool for giving feedback and defining learning objectives in the clinical setting. The aim of the present study is to identify facilitating and inhibiting factors. The results will provide information to improve the use of this learning tool to effectively promote learning in the workplace. First, all users must be trained in its use. In particular, it is important to provide immediate and specific feedback that identifies opportunities for improvement and sets achievable learning goals. Documentation should be user-friendly and provide an overview of the learning process. WBAs should not be perceived as a duty, but as a tool for valuable learning moments.

Pediatric Tularemia-A Case Series From a Single Center in Switzerland.

Background: The incidence of tularemia has recently increased throughout Europe. Pediatric tularemia typically presents with ulceroglandular or glandular disease and requires antimicrobial therapy not used in the empirical management of childhood acute lymphadenitis. We describe the clinical presentation and course in a case series comprising 20 patients. Methods: This is a retrospective analysis of a single-center case series of microbiologically confirmed tularemia in patients <16 years of age diagnosed between 2010 and 2021. Results: Nineteen patients (95%) presented with ulceroglandular (n = 14) or glandular disease (n = 5), respectively. A characteristic entry site lesion (eschar) was present in 14 (74%). Fever was present at illness onset in 15 patients (75%) and disappeared in all patients before targeted therapy was initiated. The diagnosis was confirmed by serology in 18 patients (90%). While immunochromatography was positive as early as on day 7, a microagglutination test titer 1:≥160 was found no earlier than on day 13. Sixteen patients (80%) were initially treated with an antimicrobial agent ineffective against F. tularensis. The median delay (range) from illness onset to initiation of targeted therapy was 12 (6-40) days. Surgical incision and drainage were ultimately performed in 12 patients (60%). Conclusions: Pediatric tularemia in Switzerland usually presents with early, self-limiting fever and a characteristic entry site lesion with regional lymphadenopathy draining the scalp or legs. Particularly in association with a tick exposure history, this presentation may allow early first-line therapy with an agent specifically targeting F. tularensis, potentially obviating the need for surgical therapy.

Preparedness for Life-Threatening Situations in a Pediatric Tertiary-Care University Children's Hospital: A Survey.

Pediatric nurses and physicians are rarely exposed to life-threatening events. Understanding the needs of clinicians is key for designing continuing training programs. A survey exploring preparedness to manage life-threatening events as well as training needs was mailed to all clinically active nurses and physicians at a tertiary-level referral children's hospital. Overall, 469 participants out of 871 answered the questionnaire (54% response rate). Respondents felt well or very well (nurses 93%, physicians 74%) prepared to recognize a deteriorating child and rated their theoretical understanding (70% well or very well prepared) of how to manage life-threatening situations significantly higher (p < 0.0001) than their cardiopulmonary resuscitation (CPR) preparedness (52% well or very well prepared). Both perceived theoretical understanding (p < 0.0001) and CPR preparedness (p < 0.002) were rated higher among nurses than physicians. Arrhythmias, shock, cardiac arrest and airway management constitute main areas of perceived training need. In conclusion, although a majority of pediatric nurses and physicians felt sufficiently trained to recognize a deteriorating child, their perceived ability to actively manage life-threatening events was inferior to their theoretical understanding of how to resuscitate a child. A high degree of institutional confidence and identification of areas of training need provide a good foundation for customizing future continuing education programs.

Chromosomal Heterogeneity of the G-401 Rhabdoid Tumor Cell Line: Unusual Partial 7p Trisomy.

Rhabdoid tumor is a very aggressive and hardly curable pediatric malignancy. It commonly starts in the kidneys but also can occur in the brain, liver, and other organs. The treatment of this tumor usually involves a combination of surgery, radiation, and chemotherapy. Because this tumor is rare, there is still limited experience with a defined standard of care. Cytogenetic analysis is an important routine method to monitor chromosomal aberrations. We have analyzed metaphases of the G-401 rhabdoid tumor cell line. In these cells we have observed metaphases with derivative chromosome 12 arising from partial trisomy 7p. With increasing passage number the numbers of metaphases having this derivative chromosome 12 were found to be higher. In passage number 2 only one metaphase had this pathological chromosome 12. By passage number 10 and passage number 15 about 25 and 95% of this derivative chromosome 12 were found, respectively. We were able to subclone G-401 cells by limiting dilutions and successfully separated cells having apparently normal karyotypes from cells having derivative chromosome 12. Using the cell proliferation assay we showed that clones possessing the derivative chromosome 12 grew more rapidly than clones with normal chromosomes. The cell cycle analysis confirmed this observation. Overall, in this study we describe for the first time a 7p triplication in a rare rhabdoid tumor of kidney. Both types of clones described in this study could be used as a preclinical model to study the involvement of partial chromosome 7 alterations in the development of rhabdoid tumors.

Dissection of the appendix with ultrasound-activated scalpel: an experimental study in pediatric laparoscopic appendectomy.

BACKGROUND: The aim of this study was to examine mechanical, microbiologic, and morphologic changes of the appendicle rim to assess if it is appropriate to dissect the appendix with the ultrasound-activated scalpel (UAS) during laparoscopic appendectomy. MATERIALS AND METHODS: After laparoscopic resection of the appendix, using conventional Roeder slings, we investigated 50 appendicle rims with an in vitro procedure. The overall time of dissection of the mesoappendix with UAS was noted. Following removal, the appendix was dissected in vitro with the UAS one cme from the resection rim. Seal-burst pressures were recorded. Bacterial cultures of the UAS-resected rim were compared with those of the scissors resected rim. Tissue changes were quantified histologically with hematoxylin and eosin (HE) stains. RESULTS: The average time to dissect the mesoappendix was 228 seconds (25-900). Bacterial culture growths were less in the UAS-resected probes (7 versus 36 positive probes; (p > 0.01). HE-stained tissues revealed mean histologic changes in the lamina propria muscularis externa of 2 mm depth. The seal-burst pressure levels of the appendicle lumen had a mean of 420 mbar. Seal-burst pressures and depths of histologic changes were not dependent on the different stages of appendicitis investigated, gender, or age groups. Seal-burst pressure levels were not related to different depths of tissue changes (P = 0.64). CONCLUSIONS: The UAS is a rapid instrument for laparoscopic appendectomy and appears to be safe with respect to stability, sterility and tissue changes. It avoids complex time consuming instrument change manoeuvres and current transmission, which may induce intra- and postoperative complications. Our results suggest that keeping a safety margin of at least 5 mm from the bowel would be sufficient to avoid thermal damage.