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Abstract Background The COVID-19 pandemic disrupted traditional medical education, prompting innovative teaching methods for practical skills training. The teledidactic TELUS ultrasound course, launched in 2020–2021, aimed to provide remote instruction in ultrasound techniques. Objective This study assesses the long-term impact of the teledidactic ultrasound course conducted during the study years on current clinical practice. Methods In 2024, a follow-up survey was conducted with former TELUS course students now practicing as physicians across various specialities. Participants rated their confidence in ultrasound examinations and its frequency in practice. Results 21 out of 30 participants (70%) completed the survey. 71.4% rated the course experience as excellent (5/5 points). Most reported significant learning gains, especially in the FAST module. While all agreed the course enhanced their ultrasound skills, its impact on patient care received mixed reviews. Frequency of ultrasound use varied widely among specialities, with high use in surgery and internal medicine but less in psychiatry, neurology, and ophthalmology. Notably, 42,9% had not pursued further ultrasound training post-course. Conclusion The teledidactic ultrasound course effectively provided remote education, integrating skills into practice. Mixed reviews on patient care impact and speciality-specific ultrasound use suggest sustained integration depends on relevance and ongoing education. Self-assessment results support online ultrasound courses, indicating potential use in resource-limited or geographically constrained settings.

Abstract Background We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration. Methods We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1–2), moderate (grade 3–4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality. Results In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3–4) and good image quality (median 4; interquartile range 4–4). Conclusion DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs. Relevance statement Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated. Key Points A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI. Graphical Abstract

Abstract Background Point-of-care ultrasound (POCUS) is rapidly gaining prominence in various clinical settings. As its use becomes more widespread, there is a growing need for comprehensive ultrasound training in medical education to ensure that future healthcare professionals are proficient in this essential diagnostic tool. Objective This study is the first attempt by the University of Bonn to seamlessly integrate ultrasound courses and the use of ultrasound devices into the regular activities of final year medical students and to evaluate the usage of these devices. Methods A total of forty students in their practical year were provided with a hendheld ultrasound device for a period of four months. During this time, they were invited to take part in eight optional ultrasound courses in which they acquired images and those images were rated using a specially developed rating system. At the end of the tertial, students were able to take part in a voluntary survey on the use of the equipment. Results Participation in the optional ultrasound courses was well received, with the Introduction and FAST module drawing the largest number of participants (29). Among the ultrasound images acquired by students, those of the lungs obtaining the highest rating, with 18.82 (SD ± 4.30) points out of 23 points, while the aorta and vena cava images scored lowest, with an average of 16.62 (SD ± 1.55) points. The overall mean score for all images was 17.47 (SD ± 2.74). Only 21 students responded to the survey. Of the participating students, 67% used the device independently four times or fewer during the tertial. Conclusion The study aimed to enhance the BI-POCUS curriculum by improving students' ultrasound skills during their practical year. However, device usage was lower than expected, with most students using it only once a month or less. This raises concerns about the justification of the effort and resources. Future initiatives will focus on technical improvements, better login data provision, and closer monitoring of usage and progress, emphasizing the need for practical ultrasound training in medical education.

Spontaneous coronary artery dissection (SCAD) is a relevant non-atherosclerotic cause of acute coronary syndrome with a complex genetic architecture. Recent discoveries have highlighted the potential role of miRNAs and protein-coding genes involved in the processing of small RNAs in the pathogenesis of SCAD. Furthermore, there may be a connection between SCAD and the increased cardiovascular risk observed in fragile X premutation carriers as well as a correlation with pathogenetic variants in genes encoding for collagen and extracellular matrix, which are related to connective tissue disorders (CTDs). In our cohort of 15 Italian SCAD patients, a total of 37 rare variants were identified in 34 genes using whole exome sequencing (WES) and TRIO-WES analysis when both parents were available. Three likely pathogenic/pathogenetic variants were found in genes previously associated with SCAD and CTDs (COL3A1, COL1A2, and SMAD3) and 26 variants of uncertain significance in genes previously associated with SCAD and CTDs. TRIO-WES analysis revealed 7 de novo variants, 1 of which was found in a potential novel candidate gene (DROSHA). In addition, a premutation allele of 55 ± 2 CGG repeats in the promoter of the FMR1 gene was identified in two related SCAD patients by test for CGG-repeat expansions in the 5′-UTR of the FMR1 gene. Our findings suggest various potential mechanisms such as mRNA toxicity, miRNA regulation, alteration of collagen, and the extracellular matrix architecture, all of which could disrupt vascular homeostasis, and finally, WES and TRIO-WES have proven to be the most powerful approaches for characterizing the genetic background of SCAD.

Abstract Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl − 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.

Abstract Background In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2–8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate. Methods A two-center prospective study in PRD patients aged 2–18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1–9 (maximum concentration; Cmax), and 10–14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test. Results Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L). Conclusion This study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure. Trial registration NCT04042792 , registered 02.08.2019.

Background: Intravenous arginine vasopressin is increasingly used for the treatment of critically ill children. It bears the risk of hyponatraemia with potential severe long-term sequelae, but data on hyponatraemia as a side effect of continuous vasopressin infusion for paediatric intensive care patients is scarce. Methods: In this retrospective analysis performed at a tertiary care paediatric intensive care unit with 2000 annual admissions, patients were included if they were treated with intravenous vasopressin between 2016 and 2022. Baseline sodium concentrations, lowest sodium concentrations during arginine vasopressin treatment, and time to lowest sodium concentration (nadir) were derived. Results: In total, 170 patients with a median age of 4 months [interquartile range, IQR, 0–33] were included, 92.4% underwent surgery, and 28.8% died. Median arginine vasopressin dose rate was 0.027 IU/kg/h [0.019–0.036] and arginine vasopressin was started 3.2 [0–26] h after intensive care admission. Median arginine vasopressin application duration was 13.6 h [6.2–32.6]. Baseline sodium was 141 mmol/L [138–145], and lowest median sodium during arginine vasopressin infusion was 137 mmol/L [132–141] (nadir at 8.4 h [1.0–28.1] after arginine vasopressin start). Hyponatraemia (

Given the ongoing COVID-19 pandemic, there is a need to identify SARS-CoV-2 and to differentiate it from other respiratory viral infections, especially influenza A and B, in various critical settings. Since their introduction, the use of rapid antigen tests has spread worldwide, but there is variability in their diagnostic accuracy. In the present study, we evaluated the clinical performance of the ID NOW™ COVID-19 2.0, a molecular point-of-care test (POCT) based on enzymatic isothermal amplification for the differential diagnosis of SARS-CoV-2 and influenza A/B in a pediatric emergency setting. A cohort of pediatric patients admitted between December 2022 and February 2023 were simultaneously tested with the POCT and standard laboratory molecular assay. Our findings showed high negative agreement of the POCT assay across the different age groups for SARS-CoV-2, influenza A, and influenza B (more than 98.0%), while its positive agreement varied significantly for the abovementioned viral species from 50.0% to 100%. These results highlight the potential of the ID NOW™ COVID-19 2.0 POCT assay as a reliable and rapid tool for excluding SARS-CoV-2 and influenza A/B infections in symptomatic pediatric patients, although its variable positive agreement suggests a need for confirmatory RT-qPCR testing in certain clinical and epidemiological settings in order to ensure accurate diagnosis and appropriate patient management.

BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30–35 weeks and a post-natal age of 0–14 days (“subpopulation of clinical concern”), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough 80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h−1 (CV 19%) for CHILD-IVITAB vs. 1.56 h−1 (CV 43%) for STROMECTOL®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults.

IntroductionHigh repeat expansion (HRE) alleles in C9orf72 have been linked to both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); ranges for intermediate allelic expansions have not been defined yet, and clinical interpretation of molecular data lacks a defined genotype–phenotype association. In this study, we provide results from a large multicenter epidemiological study reporting the distribution of C9orf72 repeats in healthy elderly from the Italian population.MethodsA total of 967 samples were collected from neurologically evaluated healthy individuals over 70 years of age in the 13 institutes participating in the RIN (IRCCS Network of Neuroscience and Neurorehabilitation) based in Italy. All samples were genotyped using the AmplideXPCR/CE C9orf72 Kit (Asuragen, Inc.), using standardized protocols that have been validated through blind proficiency testing.ResultsAll samples carried hexanucleotide G4C2 expansion alleles in the normal range. All samples were characterized by alleles with less than 25 repeats. In particular, 93.7% of samples showed a number of repeats ≤10, 99.9% ≤20 repeats, and 100% ≤25 repeats.ConclusionThis study describes the distribution of hexanucleotide G4C2 expansion alleles in an Italian healthy population, providing a definition of alleles associated with the neurological healthy phenotype. Moreover, this study provides an effective model of federation between institutes, highlighting the importance of sharing genomic data and standardizing analysis techniques, promoting translational research. Data derived from the study may improve genetic counseling and future studies on ALS/FTD.