Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

Myocarditis and sports in the young: data from a nationwide registry on myocarditis-"MYKKE-Sport".

Background: Myocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young. Patient: Every patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis. Method: This study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013-June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database. Results: 58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports. Conclusion: Sports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

How users of automated vehicles benefit from predictive ambient light displays.

With the introduction of Level 3 and 4 automated driving, the engagement in a variety of non-driving related activities (NDRAs) will become legal. Previous research has shown that users desire information about the remaining time in automated driving mode and system status information to plan and terminate their activity engagement. In past studies, however, the positive effect of this additional information was realized when it was integrated in or displayed close by the NDRA. As future activities and corresponding items will be diverse, a device-independent and non-interruptive way of communication is required to continuously keep the user informed, thus avoiding negative effects on driver comfort and safety. With a set of two driving simulator studies, we have investigated the effectiveness of ambient light display (ALD) concepts communicating remaining time and system status when engaged in visually distracting NDRAs. In the first study with 21 participants, a traffic light color-coded ALD concept (LED stripe positioned at the bottom of the windshield) was compared to a baseline concept in two subsequent drives. Subjects were asked to rate usability, workload, trust, and their use of travel time after each drive. Furthermore, gaze data and NDRA disengagement timing was analyzed. The ALD with three discrete time steps led to improved usability ratings and lower workload levels compared to the baseline interface without any ALD. No significant effects on trust, attention ratio, travel time evaluation, and NDRA continuation were found, but a vast majority favored the ALD. Due to this positive evaluation, the traffic light ALD concept was subsequently improved and compared to an elapsing concept in a subsequent study with 32 participants. In addition to the first study, the focus was on the intuitiveness of the developed concepts. In a similar setting, results revealed no significant differences between the ALD concepts in subjective ratings (workload, usability, trust, travel time ratings), but advantages of the traffic light concept can be found in terms of its intuitiveness and the level of support experienced.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs.

Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.

Fam20C regulates protein secretion by Cab45 phosphorylation.

The TGN is a key compartment for the sorting and secretion of newly synthesized proteins. At the TGN, soluble proteins are sorted based on the instructions carried in their oligosaccharide backbones or by a Ca2+-mediated process that involves the cargo-sorting protein Cab45. Here, we show that Cab45 is phosphorylated by the Golgi-specific protein kinase Fam20C. Mimicking of phosphorylation translocates Cab45 into TGN-derived vesicles, which goes along with an increased export of LyzC, a Cab45 client. Our findings demonstrate that Fam20C plays a key role in the export of Cab45 clients by fine-tuning Cab45 oligomerization and thus impacts Cab45 retention in the TGN.

Balloon angioplasty of the bilateral renal arteries by Takayasu arteritis with a paclitaxel-eluting balloon.

We report about a 12-year-old girl who presented with a blood pressure difference between the extremities with the suspicion of an aortic coarctation. After imaging and laboratory tests, the diagnosis of Takayasu arteritis was made. Owing to persistent arterial hypertension despite medical treatment, we initiated a treatment with a balloon angioplasty of the renal arteries with an eluting balloon.

Ray-casting based evaluation framework for haptic force feedback during percutaneous transhepatic catheter drainage punctures.

PURPOSE: Development of new needle insertion force feedback algorithms requires comparison with a gold standard method. A new evaluation framework was formulated and tested on needle punctures for percutaneous transhepatic catheter drainage (PTCD). METHODS: Needle insertion is an established procedure for minimally invasive interventions in the liver. Up-to-date, needle insertions are precisely planned using 2D axial CT slices from 3D data sets. To provide a 3D virtual reality and haptic training and planning environment, the full segmentation of patient data is often a mandatory step. To lessen the time required for manual segmentation, we propose direct haptic volume-rendering based on CT gray values and partially segmented patient data. The core contribution is a new force output evaluation method driven by a ray-casting technique that defines paths from the skin to target structures, i.e., the right hepatic duct near the juncture with the common hepatic duct. A ray-casting method computes insertion trajectories from the skin to the duct considering no-go structures and plausibility criteria. A rating system scores each trajectory. Finally, the best insertion trajectories are selected that reach the target. Along the selected paths, force output comparison between a reference system and the new haptic force output algorithm is carried out, quantified and visualized. RESULTS: The evaluation framework is presented along with an exemplary study of the liver using the atlas data set from a reference patient. In a comparison of our reference method to a newer algorithm, force outputs are found to be similar in 99% of the paths. CONCLUSION: The proposed evaluation framework allows reliable detection of problematic PTCD trajectories and provides valuable hints to improve force feedback algorithm development.

Encephalopathy and sinustachycardia in childhood--a possible differential diagnosis.

We report on a 7-year-old girl with generalized seizures, somnolence, fever, and respiratory distress. The increase of sinus tachycardia with good hydration, sufficient analgesia, and hyperthermia in our patient led to the determination of thyroid hormones, and therefore finally to the diagnosis of a thyrotoxic crisis in Graves' disease. Thyrotoxic crisis is a very rare but severe disease with an incidence of 0.1/100,000-3/100,000 among children. Important differential diagnoses of hyperthyroidism are Hashimoto thyroiditis, paraneoplastic thyroid-stimulating hormone production, thyroid autonomy, as well as central hyperthyroidism. Although symptoms disappear by thyrostatic therapy (thiamazole, carbimazole, dexamethasone), a euthyroid status could only be achieved by thyroidectomy. Thyrotoxic crisis should be considered a differential diagnosis in case of resistant unexplained sinus tachycardia, seizures, and encephalopathy. Immediate and adequate therapy contributes significantly to a reduction in the high morbidity and mortality rates. A combination of several treatment approaches for hyperthyroidism can lead to a successful outcome.