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Background: Against the background of inadequate healthcare provision for children and adolescents with post-COVID-19 syndrome (PCS), a model project was initiated in Bavaria (PoCoKiBa: Post-COVID Kids Bavaria), offering specialized diagnostics and care. The aim of this study was to explore and describe the experiences and satisfaction of children and adolescents with PCS, as well as their parents, with the healthcare provided in the model project., Methods: From October to December 2022, seven focus group discussions were conducted via video conference or in person with a total of 32 participants (19 children/adolescents, twelve mothers, one father). These represented 28 children and adolescents affected by PCS (aged 7 to 17 years). The focus group discussions were recorded, transcribed and analysed using qualitative content analysis., Results: Study participants talked about their experiences with the care they received within and beyond the model project, continuity of care, communication between doctors and patients, patient information, and the accompanying study. At the sites of the model project, patients found physicians who spent more time with their patients and took them seriously. Following diagnosis, some patients have benefited from recommendations for therapeutic services or everyday behaviours, while others complained about a lack of treatment suggestions or support for dealing with PCS in their everyday life., Discussion: The experiences of study participants with the medical care of their PCS symptoms within or beyond the model project mirror the well-known challenges of healthcare provision. There is considerable room for improvement in the care of children and adolescents with PCS, particularly in the organization of the complex diagnostic process, which involves several organ systems, and in the provision of targeted information to patients and families affected., Conclusion: The supply of healthcare services, as established and offered in the PoCoKiBa model project, is crucial for families with a child affected by PCS, since it can offer expertise in diagnosis and treatment that is currently not available in routine health care., (Copyright © 2024. Published by Elsevier GmbH.)

Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future. In this case-control study, we investigated 29 consecutive KD patients [20 male, median current age, 7.9 years; median follow-up duration, 5.7 years] and a group of 29 healthy matched controls (CON) [19 male, median current age, 10.8 years]. They were assesed and compared for CAA, LVFS, GCS, GLS, coronary artery (CA) Z scores, carotid intima-media thickness (IMT) and coronary artery IMT by high-resolution transthoracic echocardiography (hrTTE). Coronary artery IMT (caIMT) was significantly higher in patients with a maximal CA Z score > 2.5 in acute KD than in CON: KD caIMT: 0.62 mm [IQR, 0.57-0.72 mm] vs. 0.53 mm [0.51-0.60 mm], p = 0.043. CAAs were found in 15 (51.7%) patients with acute KD. The maximal median LCA Z score in acute KD was 2.57z [IQR, 1.93-3.2z] and in follow-up -0.39z [IQR, -1.25 to -0.36z]. There was no significant difference in carotid IMT between KD patients and CON. Signs of CA intima-media thickening were detected by hrTTE in patients with a maximal CA Z score > 2.5 in acute KD. These data indicate that these patients may be at risk for cardiovascular sequale even in the absence of permanent CA luminal abnormalities. Therefore long-term follow-up of this group of KD patients may be required., (© 2024. The Author(s).)

Introduction: Acquired QT interval prolongations due to drug side effects can result in detrimental arrhythmia. Maternal use of placenta-permeable drugs may lead to fetal exposure, thus leading to an increased risk of neonatal QT prolongation and arrhythmia. Objectives: This study aimed to evaluate the influence of maternal QT-prolonging medication on the neonatal QT interval. Methods: In the prospective KUNO-Kids health study, an ongoing population-based birth cohort, we classified maternal medications according to the known risk of QT interval prolongation. Effects on the neonatal QT interval were tested by linear regression analyses, correcting for perinatal confounders (birth weight, gestational age, birth mode, and age at ECG recording). Subgroup analyses were performed for selective serotonin reuptake inhibitors, proton pump inhibitors, and antihistamine dimenhydrinate. Logistic regression analysis was performed using a QTc of 450 ms as the cut-off value. Results: A total of 2,550 pregnant women received a total of 3,990 medications, of which 315 were known to increase the risk of QT prolongation, resulting in 105 (4.1%) neonates exposed in the last month of pregnancy. Overall, the mean age of the neonates at ECG was 1.9 days and the mean QTc (Bazett) was 414 ms. Univariate (regression coefficient -2.62, p = 0.288) and multivariate (regression coefficient -3.55, p = 0.146) regression analyses showed no significant effect of fetal medication exposure on the neonatal QT interval, neither in the overall nor in the subgroup analysis. Logistic regression analysis showed no association of exposure to maternal medication with an increased risk of neonatal QT interval prolongation (OR (odds ratio) 0.34, p = 0.14). Conclusion: The currently used maternal medication results in a relevant number of fetuses exposed to QT interval-prolonging drugs. In our cohort, exposure was found to have no effect on the neonatal QT interval., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Michel, Potapow, Dechant, Brandstetter, Wellmann, Köninger, Melter, Apfelbacher, Kabesch and Gerling.)

Occupational exposure to veterinary antibiotics in hen houses at poultry feeding farms was demonstrated by biomonitoring campaigns in the past. The objective of this study was to investigate pharmacokinetics of three uptake routes: dermal, oral and inhaled. In an open-label cross-over study, six healthy volunteers were exposed to single occupational relevant doses of enrofloxacin. Plasma and urine samples were analysed for enrofloxacin and ciprofloxacin. Physiologically based pharmacokinetic (PBPK) modelling based on bioanalysis data showed underestimation for the elimination rate in comparison to experimental data pointing towards a lack of sufficient ADME information and limitations of available physico-chemical properties of the parent drug. The data obtained in this study indicate that oral uptake with its various sources, e.g. airborne enrofloxacin, direct hand-mouth contact, is the major source for occupational exposure to enrofloxacin in hen houses. Dermal exposure was considered negligible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Some children and adolescents suffer from late effects of a SARS-CoV-2 infection despite a frequently mild course of the disease. Nevertheless, extensive care for post-COVID-19 condition, also known as post-COVID-19 syndrome, in children and young people is not yet available. A comprehensive care network, Post-COVID Kids Bavaria (PoCo), for children and adolescents with post-COVID-19 condition has been set up as a model project in Bavaria, Germany., Objective: The aim of this study is to evaluate the health care services provided within this network structure of care for children and adolescents with post-COVID-19 condition in a pre-post study design., Methods: We have already recruited 117 children and adolescents aged up to 17 years with post-COVID-19 condition who were diagnosed and treated in 16 participating outpatient clinics. Health care use, treatment satisfaction, patient-reported outcomes related to health-related quality of life (the primary endpoint), fatigue, postexertional malaise, and mental health are being assessed at different time points (at baseline and after 4 weeks, 3 months, and 6 months) using routine data, interviews, and self-report questionnaires., Results: The study recruitment process ran from April 2022 until December 2022. Interim analyses will be carried out. A full analysis of the data will be conducted after follow-up assessment is completed, and the results will be published., Conclusions: The results will contribute to the evaluation of therapeutic services provided for post-COVID-19 condition in children and adolescents, and avenues for optimizing care may be identified., International Registered Report Identifier (irrid): DERR1-10.2196/41010., (©Chiara Rathgeb, Maja Pawellek, Uta Behrends, Martin Alberer, Michael Kabesch, Stephan Gerling, Susanne Brandstetter, Christian Apfelbacher. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.04.2023.)

Background: Progressive enlargement of the coronary artery (CA) diameters on serial echocardiography can support diagnosis of Kawasaki's disease (KD) even CA dimensions are within the normal range., Methods: A single-center, retrospective study compared mean Z-scores of the proximal CA internal diameters in children hospitalized with non-KD febrile illnesses (FCs) with those of KD patients., Results: A total of 223 patients with suspicion of KD have been admitted over a period of 16 years and data were evaluable for 176 children. Distributions for age, sex, and body surface area were similar for both groups. FC had a significantly shorter duration of hospitalization, higher levels of hemoglobin, lower levels of liver transaminases, and segmented neutrophils, respectively. The majority of FC patients (75/82, 91.5%) had normal CA Z-scores ( p  < 0.001) and only 3 (3.7%) had CA Z-score ≥2.5 standard deviation (SD). In KD, subjects (46/94, 49.5%) had a CA dilation (Z-score ≥2.5 SD) and the maximum CA Z-score (Zmax) was significantly higher compared with FC patients ( p  < 0.001). On serial echocardiograms, FC patients showed a mild decrease, whereas KD patients developed a significant increase of CA Zmax ( p  < 0.001). Seven KD patients had a segmental dilation of a CA which has been confirmed by cardiac catheter. In FC, no segmental dilation of any CA was documented by echocardiography., Conclusion: This study found that mean CA dimensions in FCs were smaller and did not increase in serial echocardiograms compared with KD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication of infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently, neutralising autoantibodies against inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist (IL-1Ra) were found in adult patients with critical COVID-19. The aim of this study was to investigate the role of such autoantibodies in MIS-C., Methods: In this multicentre, retrospective, cohort study, plasma and serum samples were collected from patients (0-18 years) with MIS-C (as per WHO criteria) treated at five clinical centres in Germany and Spain. As controls, we included plasma or serum samples from children with Kawasaki disease, children with inactive systemic juvenile idiopathic arthritis, and children with suspected growth retardation (non-inflammatory control) across four clinical centres in Germany and Spain (all aged ≤18 years). Serum samples from the CoKiBa trial were used as two further control groups, from healthy children (negative for SARS-CoV-2 antibodies) and children with previous mild or asymptomatic COVID-19 (aged ≤17 years). MIS-C and control samples were analysed for autoantibodies against IL-1Ra and progranulin, and for IL-1Ra concentrations, by ELISA. Biochemical analysis of plasma IL-1Ra was performed with native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1β-signalling reporter assay., Findings: Serum and plasma samples were collected between March 6, 2011, and June 2, 2021. Autoantibodies against IL-1Ra could be detected in 13 (62%) of 21 patients with MIS-C (11 girls and ten boys), but not in children with Kawasaki disease (n=24; nine girls and 15 boys), asymptomatic or mild COVID-19 (n=146; 72 girls and 74 boys), inactive systemic juvenile idiopathic arthritis (n=10; five girls and five boys), suspected growth retardation (n=33; 13 girls and 20 boys), or in healthy controls (n=462; 230 girls and 232 boys). Anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, except in one patient who had additional IL-1Ra-specific IgM antibodies. Autoantibodies against progranulin were only detected in one (5%) patient with MIS-C. In patients with MIS-C who were positive for anti-IL-1Ra antibodies, free plasma IL-1Ra concentrations were reduced, and immune-complexes of IL-1Ra were detected. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1Ra was observed in all patients with MIS-C who were positive for anti-IL-1Ra antibodies. Anti-IL-1Ra antibodies impaired IL-1Ra function in reporter cell assays, resulting in amplified IL-1β signalling., Interpretation: Anti-IL-1Ra autoantibodies were observed in a high proportion of patients with MIS-C and were specific to these patients. Generation of these autoantibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra. These autoantibodies impair IL-1Ra bioactivity and might thus contribute to increased IL-1β-signalling in MIS-C., Funding: NanoBioMed fund of the University of Saarland, José Carreras Center for Immuno and Gene Therapy, Dr Rolf M Schwiete Stiftung, Staatskanzlei Saarland, German Heart Foundation, Charity of the Blue Sisters, Bavarian Ministry of Health, the Center for Interdisciplinary Clinical Research at University Hospital Münster, EU Horizon 2020., Competing Interests: LT has received research grants from Wilhelm Sander-Stiftung, BioNanoMed, and the Homburger Forschungsförderung programme of the University of Saarland; travel grants for meeting attendance from AbbVie, Janssen, and EUSA-Pharm; and has participated in advisory boards for Takeda, AstraZeneca, Merck, and EUSA Pharma. LT and K-DP were listed among inventors of a patent on progranulin antibodies as marker for autoimmune diseases filed by University of Saarland, which expired in 2017. CK has received consulting fees from Novartis and Swedish Orphan Biovitrum (SOBI) and receives research support from Novartis. MBö has received speakers honoraria from or participated in advisory boards for Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cyotkinetics, Medtronic, Novartis, Servier, and Vifor. HW has received honoraria (lecture fees) from Novartis and Takeda, and travel support from Octapharma and CSL-Behring. DF has received speaker fees or honoraria from Chugai-Roche, Novartis, and SOBI, and research support from Novartis, Pfizer, and SOBI. JA has received grants and travel grants for meeting attendance from SOBI and Novartis, and participated in advisory boards for SOBI and Novartis. BT has received honoraria for lectures from Nutricia Milupa and is a private shareholder of BioNTech. MK has received research support for the CoKiBa trial from Roche, who provided the diagnostic antibodies at a time when they were not yet commercially available. In addition, MK has received honoraria for lectures from Pädnetz Bayern, Ärztlicher Kreisverband, and Bayerischer Berufsverband der Kinder- und Jugendärzte, and participated in the advisory board for COVID-19 in children of the Bavarian Ministry of Health. SLB has participated in advisory boards and received honoraria for lectures from Shinogi and Pfizer. RB has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; personal fees from GlaxoSmithKline, Grifols, and CSL Behring; grants from the German Ministry of Education and Research, Competence Network on Asthma and COPD, Sander Stiftung, Schwiete Stiftung, Krebshilfe, and Mukosviszidose; and has a leadership role at the Alpha-1-Center in Bad Lippspringe, Germany. All other authors declare no competing interests., (© 2022 Elsevier Ltd. All rights reserved.)

Introduction:  Classic bladder exstrophy (BE) is regarded as an isolated malformation without any further anomalies, but some studies have indicated a higher incidence of cardiac anomalies. This cross-sectional study is planned to evaluate the prevalence of congenital heart defects (CHDs) and the clinical relevance for patients with BE admitted for primary closure., Materials and Methods:  Patients were prospectively recruited between March 2012 and January 2019. Patients' profiles including demographic data, results of transthoracic echocardiography (TTE), as well as essential peri- and postoperative data were assessed., Results:  Thirty-nine (25 boys and 14 girls) patients with BE (median age 61 days) underwent delayed primary bladder closure. Thirty-seven (24 boys and 13 girls) patients had received TTE 1 day before surgery. CHD was detected in 7 (18.9%) out of the 39 patients, but no clinical differences between patients with and without CHD were observed peri- or postoperatively., Discussion and Conclusion:  This prospective systematic evaluation shows an even higher rate of CHD in patients with BE than assumed previously. Although peri- and postoperative outcome did not differ between patients with and without CHD, we consider TTE an important additional method for ensuring a safe peri- and postoperative courses and a short- and long-term care for patients with CHD., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Football is the most popular sport worldwide and results in a high frequency of injuries. So far, mainly injuries in professional football have been investigated, and the literature lacks data regarding detailed injury epidemiology and current prevention data in amateur football tournaments., Materials and Methods: A prospective cohort study investigated an international amateur football tournament, the UEFA Regions' Cup, which took place in 2019 in Germany. Injury epidemiology, current prevention strategies of the teams and the implementation of the UEFA concussion protocol were investigated in detail by means of standardized injury definitions and data samples for football (Fuller et al., Scand J Med Sci Sports 16:83-92, https://doi.org/10.1111/j.1600-0838.2006.00528.x , 2006)., Results: 138 player of 8 teams participated in this study, while 39 players were excluded. Overall injury incidence was 12.5 per 1000 h total football exposure, 43.5 per 1000 h for match exposure. No injuries were registered during training. Injury prevalence was 14.1% per player and 1.1 injuries per match were registered. The lower extremity was predominantly affected by injuries (71.4%) and the majority of injuries (78.6%) were non-severe injury types like contusions (50%) and sprains (18.2%). Two head injuries, one contusion and one skin lesion, were handled by the guidelines of the UEFA concussion protocol. 44.4% of the players indicated at least one previous injury before tournament, 45.3% of them during the last two football seasons before start of the tournament. Injury prevention performance was included in all participating teams during the tournament by warm up or training strategies (100%). During the warm-up program just 5 exercises of the FIFA 11 + program was detected by this investigation in participating teams to be done by more half of the teams. Running exercises were the most frequently performed exercises, while trunk muscle exercises were less represented (14.3%)., Conclusion: This study presents for the first time epidemiological injury and prevention data of the UEFA Regions Cup. Injury incidence was higher compared to injury reports of regular seasons, but lower compared to other amateur football tournaments. Currently used prevention programs revealed trunk muscle exercises as often neglected., (© 2021. The Author(s).)

Loss-in-weight feeders are an integral part of most continuous manufacturing processes, ensuring a constant mass flow. The feeders cause a significant degree of back-mixing in such lines. Understanding back-mixing is essential for the treatment of disturbances. However, feeders refilled semi-continuously contradict the common theory assuming steady-state. This study aims at understanding dynamic back-mixing and related phenomena. Low filling levels of a feeder are investigated using a fluorescent tracer. These investigations prove an impact of the addition of material probably caused by a non-uniform draw-in of the screws and dead material in the hopper. In turn, the dead material accounts for up to 50 % of the material in the hopper. Possible evidence of dead zones at higher filling levels and in feeders from literature are discussed additionally. Steady-state models from literature are extended to represent the observations and back-mixing at all filling levels. This extension reduces the root-mean-squared deviation of the model from the experimental data by 41%. The model predicts different responses to similar disturbances depending on the filling. This state-dependent back-mixing and the observed dead zones are challenging for diverting non-conforming material and material traceability. Therefore, these phenomena should be considered in selecting and operating feeders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. Results: We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children ( n = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Conclusions: Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population., Competing Interests: JN was employed by the company Maganamed Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laub, Leipold, Toncheva, Peterhoff, Einhauser, Neckermann, Borchers, Santos-Valente, Kheiroddin, Buntrock-Döpke, Laub, Schöberl, Schweiger-Kabesch, Ewald, Horn, Niggel, Ambrosch, Überla, Gerling, Brandstetter, Wagner, Kabesch and Corona Virus Antibodies in Children from Bavaria (CoKiBa) Study Group.)

Background: With the increased training loads at very early ages in European elite youth soccer, there is an interest to analyse coronary artery remodelling due to high-intensity exercise., Design and Methods: Prospective echocardiographic study in 259 adolescent elite male soccer players and 48 matched controls., Results: The mean age was 12.7 ± 0.63 years in soccer players and 12.6 ± 0.7 years in controls (p > 0.05). Soccer players had significant greater indexed left ventricular mass (93 ± 13 g/m2 versus 79 ± 12 g/m2, p = 0.001). Both coronary arteries origin could be identified in every participant. In soccer players, the mean diameter of the left main coronary artery was 3.67 mm (SD ± 0.59) and 2.61 mm (SD ± 0.48) for right main coronary artery. Controls showed smaller mean luminal diameter (left main coronary artery, p = 0.01; right main coronary artery, p = 0.025). In soccer players, a total of 91% (n = 196) and in controls a total of 94% (n = 45) showed left main coronary artery z scores within the normal range: -2.0 to 2.0. In right main coronary artery, a pattern of z score values distribution was comparable (soccer players 94%, n = 202 vs. controls 84%, n = 40). A subgroup of soccer players had supernormal z score values (>2.0 to 2.5) for left main coronary artery (9%, n = 19, p = 0.01) and right main coronary artery (6%, n = 10, p = 0.025), respectively., Conclusion: Elite soccer training in early adolescence may be a stimulus strong enough to develop increased coronary arteries diameters. In soccer players, a coronary artery z score >2.0-2.5 might reflect a physiologic response induced by multiannual high-intensity training.

Kawasaki disease (KD) is an acute vasculitis predominantly affecting the small arteries of young children. Up to 25% of untreated patients suffer from coronary artery (CA) complications. Early diagnosis and treatment is mandatory in incomplete KD to reduce the risk of coronary involvement. Between 2002 and 2018, 124 patients have been diagnosed suffering from KD at the University Children's Hospital Regensburg (KUNO). We assessed luminal diameters of both CAs normalized as Z-scores by 2D-echocardiography. A total of 94 patients were analyzed. Of them, 31 (33%) were affected by an incomplete form of KD. In 24 children (26%), serial echocardiography was necessary in order to confirm diagnosis. Mean Z-scores for the left main coronary artery (LMCA), right main coronary artery (RMCA), and left anterior descending artery increased significantly between the initial (LMCA 0.79z, RMCA 0.15z, LAD 0.49z) and second (LMCA 1.69z, RMCA 0.99z, LAD 1.69z) examination (p < 0.05).Conclusion:To confirm diagnosis of KD, it might not be necessary to detect dilation or aneurysms. Our observation suggests that patients suspected having KD should be monitored with serial echocardiography in order to detect a possible enlargement of the CA diameters, even if Z-scores are within the normal range. What is Known: • Kawasaki disease (KD) is an acute vasculitis predominantly affecting the small arteries of young children. Up to 25% of untreated patients suffer from coronary artery (CA) complications. • Due to less classic clinical criteria in patients with incomplete KD, the risk for CA pathology is even higher. What is New: • A significant progression of patients' CA Z-scores in serial echocardiographic measurements may be helpful to ensure diagnosis of KD early even if Z-scores are within the normal range. • Twenty-seven patients (90%) with incomplete KD could be diagnosed within 10 days of fever, early enough to prevent significantly higher rates of CA aneurysm.

Recent studies showed contrasting findings in morphological changes due to competitive soccer in adolescent players (SP). We present a prospective study in 315 consecutive adolescent (10-14 years) male elite SP and 53 healthy matched active controls (CON). All participants underwent a complete transthoracic two-dimensional echocardiography (TTE). The mean age in SP was 12.8 ± 0.65 years compared to 12.6 ± 0.8 years in CON. For all left ventricular (LV) dimensions, mean Z-score values were higher in SP. There was a significant Z-score increase in interventricular septum diastolic diameter (2.47z vs. 1.62z, p < 0.05), left ventricular posterior wall diastolic and systolic diameter (1.15z vs. 0.47z, p < 0.05 and 1.05z vs. - 0.4z, p < 0.05). Athletes had significant greater LV mass indexed for BSA (94 ± 12 g/m 2 vs. 81 ± 13 g/m 2 , p < 0.05). There was no significant difference in LV function or diameters. Conclusion: Our findings suggest that elite soccer training in adolescent male is a type of sport predominantly related to cardiac resistance remodeling. Adolescent SP may develop supernormal left ventricular wall dimensions (+ 2.0 to + 2.5z). If in SP Z-scores, any LV dimension above + 2.5 is measured, primary or secondary cardiomyopathies should be excluded. What is Known: • Morphological cardiac adaptation in response to exercise depends on the type, duration, and intensity of training. • Morphological and functional changes due to competitive sports (athlete's heart) occur even in pre-adolescent athletes. What is New: • Our findings point out that German elite soccer training in adolescent male (10-14 years of age) is a type of sport predominantly related to cardiac resistance remodeling. • If in an adolescent competitive soccer player any LV dimension Z-score value above + 2.5 is measured, a primary or secondary cardiomyopathy should be excluded.

Purpose: Injury data of professional soccer players obtained from media reports are frequently used in scientific research, but the accuracy of such data is still unclear., Patients and Methods: Injuries of professional soccer players of the German first and second league were documented by continuously screening media reports over one season (2015-2016). After the season, the validity of media-reported injuries was anonymously analyzed by the team physicians of 8 different soccer clubs., Results: A total of 255 injuries of 240 players of 8 professional soccer teams had been published online, of which 146 were confirmed by the team doctors as correct, yielding a rate of 57.3% of confirmed media-reported injuries. In addition, 92 injuries without media registration were detected and added to the online statistics, resulting in 347 injuries and an overall weak validity of media-based data of 42.1%. Statistical analysis showed that the validity of media-reported injury data depended on both the individual soccer club and the body site affected by injury: publications on knee injuries (78.2%) had a higher validity than those on foot injuries (46.2%), and publications on severe injuries had a higher validity (joint dislocation: 100%; ligament rupture: 82.9%; fracture: 73.3%) than those on minor injuries. Publications on specific severe soccer injuries, such as anterior cruciate ligament (ACL) injuries, had a validity of 100%., Conclusion: Media-based injury data were only valid for a few severe injury types such as ACL injuries. In daily soccer routine and scientific research, media-based data should thus only be used in combination with specific criteria or verification processes., Competing Interests: Werner Krutsch reports being a member of medical committees in different football associations: German Football Association, German Football League and Bavarian Football Association but states all memberships are no conflict of interest to this study and this article. The authors report no other conflicts of interest in this work., (© 2020 Krutsch et al.)

We report on a 12-month-old girl with an ectopic atrial tachycardia successfully treated with the combination of a beta blocking agent and Ivabradine that acts on cardiac pacemaker cells by selectively inhibiting the I f channel. Standard therapy had failed to control the tachycardia before. No side effects attributable to Ivabradine were noticed. Due to its mechanism of action Ivabradine is a promising novel agent for the therapy of tachycardia due to increased automaticity. Reports on the use of Ivabradine in young children or infants are rare, but show promising results for congenital junctional ectopic tachycardia. This report adds the second case of ectopic atrial tachycardia in this age group and novel treatment with Ivabradine to the literature., (Copyright © 2020 Michel, Heißenhuber, Wellmann, Melter and Gerling.)

Introduction: Newborn sudden infant death syndrome (SIDS) has failed to decrease in the last decades, and a third of the neonatal cases occurred within the first 6 days of life. The long QT syndrome (LQTS) is a genetic disease with a prevalence of 1 in 2,000 live births and contributes to almost 10% of SIDS cases. Early identification of LQTS through electrocardiogram (ECG) screening is likely to reduce mortality., Methods and Results: In this ongoing prospective study we evaluated 2,251 ECGs from newborns participating in the KUNO Kids birth cohort study between July 2015 and July 2018. ECGs were recorded at a mean age of 2.0 days (IQR 0 days). The QT interval was corrected for heart rate using Bazett's formula (QTc). A QTc between 451 and 460, 461-470, and >470 ms was measured in 23 (1.0), 14 (0.6), and 62 (2.8%) participants, respectively. Fourteen neonates (0.62%) were admitted and monitored because their initial QTc was ≥500 ms. In 2 genetically analyzed participants, a mutation was found. One disease-causing for LQTS type 1 and the other of unclear significance. Cascade screening revealed affected members in both families., Conclusion: A standardized neonatal ECG screening in the first days of life is able to identify neonates with a relevant transient form of prolonged QT intervals and to aid diagnosing congenital LQTS., (© 2020 The Author(s). Published by S. Karger AG, Basel.)

Today, antibiotics are essential for effective treatment of infectious diseases both in human and veterinary medicine. The increasing development and distribution of antibiotic-resistant microorganisms are subject of concern. In some sectors of animal agriculture, such as poultry feeding farms, the application of antibiotics and hence occupational exposure is inevitable. In the past, numerous studies focussed on the occurrence of antibiotic-resistant bacteria in livestock farming, but little attention was paid to the employees. The exposure of workers to antibiotics was the focus of the study detailed in this article. Four biomonitoring campaigns monitoring systemic exposure of workers to antibiotics were run at two farms over four fattening periods. Urine samples of potentially affected employees were sampled and analysed for the antibiotics of interest by liquid chromatography-mass spectrometry. The highest antibiotic concentrations detected in urine samples exceeded the minimum inhibitory concentration of some bacteria strains. In some cases, the amount of antibiotics excreted over a time-period of 24 h indicated the exceedance of the tolerable daily intake., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Chinese hamster ovary (CHO) cells are widely used for biopharmaceutical protein production. One challenge limiting CHO cell productivity is apoptosis stemming from cellular stress during protein production. Here we applied CRISPR interference (CRISPRi) to downregulate the endogenous expression of apoptotic genes Bak, Bax, and Casp3 in CHO cells. In addition to reduced apoptosis, mitochondrial membrane integrity was improved and the caspase activity was reduced. Moreover, we optimized the CRISPRi system to enhance the gene repression efficiency in CHO cells by testing different repressor fusion types. An improved Cas9 repressor has been identified by applying C-terminal fusion of a bipartite repressor domain, KRAB-MeCP2, to nuclease-deficient Cas9. These results collectively demonstrate that CHO cells can be rescued from cell apoptosis by targeted gene repression using the CRISPRi system., (© 2019 Wiley Periodicals, Inc.)

Background: Sudden cardiac death (SCD) in children and adolescents is rare. Several studies have reported a higher risk of SCD during athletic competition. High risk congenital coronary artery abnormalities are the second leading cause of SCD in young athletes in the USA. Echocardiographic assessment of coronary arteries has not been routinely used in screening programmes for junior athletes so far., Design: Prospective cohort study in 1045 consecutive adolescent elite football players., Methods: All athletes underwent a standardized cardiovascular screening protocol with a medical history, a physical examination, 12-lead resting electrocardiogram and a complete transthoracic 2D-echocardiography., Results: Two athletes (0.19%) showed a high-risk coronary artery abnormality (CAA) with a right coronary artery originating abnormal from the aorta and coursing inter-arterial. Low-risk CAAs were found in 16 athletes (1.53%). There was an ectasia of the left coronary artery (+3.9z and +4.3z) and a fistula from the left coronary artery in two cases (0.19%), respectively. In 1.05% ( n = 11) we found a high take-off (2.3-6.8 mm) and in one case (0.096%) there was a tangential take-off of the right main coronary artery. Variants of coronary arterial anatomy were identified in 335 of 1045 athletes (32.06%)., Conclusion: Basic pre-participation screening tests including 12-lead or exercise electrocardiogram do not safely identify high-risk CAAs. In adolescent athletes an expert cardiologist is able to describe the origin and the proximal course of the coronary arteries and identify major abnormalities in most of the cases by transthoracic 2D-echocardiography.

Purpose: Injuries are a common occurrence in football. Sufficient epidemiological data are available in professional football but not in salaried semi-professional football. This study investigates the injury incidence at different levels of semi-professional football with focus on junior football., Methods: The data were based on injury reports provided by players and medical staff over the 2015-2016 season, which corresponded to the consensus statement for data samples in football. This study investigated the injury incidence and prevalence of five skill levels of semi-professional football (the fourth to the seventh league and elite junior football)., Results: 1130 players had sustained 2630 injuries over the 2015-2016 season. The overall injury incidence was 9.7 per 1000 h football exposure; prevalence with at least one injury was 79%. The highest overall injury incidence in elite junior football was 10.4 in 1000 h football exposure. The fifth league had the lowest incidence with 9.0 in 1000 h football (p < 0.05). Traumatic injuries most often occurred in the fourth league (3.9 in 1000 h football). The body areas most affected by traumatic injury were knees, ankles and thighs. Elite junior players had a significantly higher incidence of overuse complaints (7.4 in 1000 h football) than the fourth league (5.4, p = 0.005). The body areas most affected by overuse complaints were the lower back, thigh and groin. No differences were found between the different positions on field., Conclusions: Salaried semi-professional football involves a high overall injury incidence. The highest incidence, particularly of overuse injuries, was seen in elite junior football. These findings should be incorporated in specific injury prevention training or screenings beginning in junior football. Level of evidence II.

Introduction: Extracorporeal life support in adult patients with extended intracranial hemorrhage is controversial. In pediatric patients, it has traditionally been considered a contraindication as systemic anticoagulation may worsen the hemorrhage and neurological outcome., Case History: We present a nine-year-old female patient who was admitted with extended intracranial hemorrhage after spontaneous rupture of an aneurysm. On day four after the emergency craniotomy, she required veno-arterial extracorporeal membrane oxygenation for septic shock. Using an adapted anticoagulation protocol aimed at lower activated partial thromboplastin time target values, we did not observe any new bleeding or clotting complications during systemic anticoagulation and the patient had good neurological recovery., Conclusion: Extracorporeal life support with low dose systemic anticoagulation can be considered as a treatment option in pediatric patients after craniotomy for intracranial aneurysmatic hemorrhage., (© The Author(s) 2015.)

The CRISPR/Cas9 genome editing technology has previously been shown to be a highly efficient tool for generating gene disruptions in CHO cells. In this study we further demonstrate the applicability and efficiency of CRISPR/Cas9 genome editing by disrupting FUT8, BAK and BAX simultaneously in a multiplexing setup in CHO cells. To isolate Cas9-expressing cells from transfected cell pools, GFP was linked to the Cas9 nuclease via a 2A peptide. With this method, the average indel frequencies generated at the three genomic loci were increased from 11% before enrichment to 68% after enrichment. Despite the high number of genome editing events in the enriched cell pools, no significant off-target effects were observed from off-target prediction followed by deep sequencing. Single cell sorting of enriched multiplexed cells and deep sequencing of 97 clones revealed the presence of four single, 23 double and 34 triple gene-disrupted cell lines. Further characterization of selected potential triple knockout clones confirmed the removal of Bak and Bax protein and disrupted fucosylation activity as expected. The knockout cell lines showed improved resistance to apoptosis compared to wild-type CHO-S cells. Taken together, multiplexing with CRISPR/Cas9 can accelerate genome engineering efforts in CHO cells even further., (Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Sufficient first aid equipment is essential to treat injuries on football fields. Deficits in first aid on field are still present in youth football., Methods: Injury pattern in youth football over one season and first aid equipment in youth football were analyzed, retrospectively. PRICE and ABC procedure served as basic principles in emergency management to assess the need for first aid equipment on field. Considering financial limits and adapted on youth football injuries, sufficient first aid equipment for youth football was configured., Results: 84% of 73 participating youth football teams had their own first aid kit, but the majority of them were insufficiently equipped. Team coaches were in 60% of all youth teams responsible for using first aid equipment. The injury evaluation presented 922 injuries to 1,778 youth players over one season. Frequently presented types of injury were contusions and sprains of the lower extremity. Based on the analyzed injury data in youth football, first aid equipment with 90 € is sufficient for 100% of all occurred youth football injuries., Conclusion: Current first aid equipment in youth football is insufficient. Scientific-based first aid equipment with 90 € is adequate to serve all injuries. Football coaches need education in first aid management.

Micro-organisms are known to degrade a wide range of toxic substances. How the environment shapes microbial communities in polluted ecosystems and thus influences degradation capabilities is not yet fully understood. In this study, we investigated microbial communities in a highly complex environment: the capillary fringe and subjacent sediments in a hydrocarbon-contaminated aquifer. Sixty sediment sections were analysed using terminal restriction fragment length polymorphism (T-RFLP) fingerprinting, cloning and sequencing of bacterial and archaeal 16S rRNA genes, complemented by chemical analyses of petroleum hydrocarbons, methane, oxygen and alternative terminal electron acceptors. Multivariate statistics revealed concentrations of contaminants and the position of the water table as significant factors shaping the microbial community composition. Micro-organisms with highest T-RFLP abundances were related to sulphate reducers belonging to the genus Desulfosporosinus, fermenting bacteria of the genera Sedimentibacter and Smithella, and aerobic hydrocarbon degraders of the genus Acidovorax. Furthermore, the acetoclastic methanogens Methanosaeta, and hydrogenotrophic methanogens Methanocella and Methanoregula were detected. Whereas sulphate and sulphate reducers prevail at the contamination source, the detection of methane, fermenting bacteria and methanogenic archaea further downstream points towards syntrophic hydrocarbon degradation., (© 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.)

In order to quantify the relative oral bioavailability of 3-chloropropane-1,2-diol (3-MCPD) from 3-MCPD fatty acid diesters in vivo, 1,2-dipalmitoyl-3-chloropropane-1,2-diol (3-MCPD diester) and 3-MCPD were orally applied to rats in equimolar doses. In both cases, the time courses of 3-MCPD concentrations were measured in blood, various organs, tissues and intestinal luminal contents. The results show that 3-MCPD is released by enzymatic hydrolysis from the 3-MCPD diester in the gastrointestinal tract and distributed to blood, organs and tissues. Based on the measurements in blood, the areas under the curve (AUC) for 3-MCPD were calculated. By comparing both AUC, the relative amount of 3-MCPD bioavailable from the 3-MCPD diester was calculated to be 86 % on average of the amount bioavailable following administration of 3-MCPD. In view of limited experimental data, it is justified for the purpose of risk assessment to assume complete hydrolysis of the diesters in the gastro-intestinal tract. Therefore, assessment of the extent of exposure to 3-MCPD released from its fatty acid esters should be performed in the same way as exposure to the same molar quantity of 3-MCPD.

Groundwater samples collected downgradient from a former municipal solid waste landfill near Berlin, Germany, were analyzed by GC-MS, HPLC-MS, and HPLC-NMR hyphenated techniques to comprehensively characterize the xenobiotic organic compounds (XOCs). The focus thereby was on the detection and identification of the polar XOCs which were analyzed in the extract obtained after separation of the unpolar components by pre-extraction. HPLC-NMR and HPLC-MS runs were used to identify polar XOCs on-line or to obtain preliminary structure information on the other XOCs. These compounds were then isolated by HPLC fractionation and their structures elucidated by off-line NMR and MS investigations. A variety of polar XOCs, products of the dye industry, degradation products of polyethylene glycol, and some heterocyclic compounds could be identified. Furthermore, a semi-quantitative estimation of the identified polar compounds is given.

We have developed a highly selective and sensitive method using gas chromatography-mass spectrometry with negative chemical ionization for measuring 3-chloropropane-1,2-diol (3-MCPD) in rat blood and urine. Samples were adsorbed on silica gel, extracted with ethyl acetate, and derivatized by chemical derivatization with heptafluorobutyric acid anhydride. For quantification, matrix-based calibration curves and 3-MCPD-d (5), as an isotope-labeled internal standard, were used. The relative recoveries of 3-MCPD were between 80 and 110% in most cases and the relative standard deviations were typically less than 10%, with some exceptions. The limit of quantification of the method was found to be about 2 ng/mL. In conclusion, a valuable, robust, and sensitive method for detection of 3-MCPD is now available for biokinetics studies.

Five commercially available insect sprays were applied in a model room. Spraying was performed in accordance with the manufacturers' instructions and in an overdosed manner in order to simulate worst-case conditions or an unforeseeable misuse. In addition, we examined electro-vaporizers. The Respicon aerosol monitoring system was applied to determine inhalation exposure. During normal spraying (10 seconds) and during the following 2-3 minutes, exposure concentrations ranged from 70 to 590 microg/m3 for the pyrethroids tetramethrin, d-phenothrin, cyfluthrin, bioallethrin, and the pyrethrins. Calculated inhalable doses were 2-16 microg. A concentration of approximately 850 microg chlorpyrifos/m(3) (inhalable dose: approximately 20 microg) was determined when the "Contra insect fly spray" was applied. Highest exposure concentrations (1100-2100 microg/m3) were measured for piperonyl butoxide (PBO), corresponding to an inhalation intake of 30-60microg. When simulating worst-case conditions, exposure concentrations of 200-3400microg/m3 and inhalable doses of 10-210microg were determined for the various active substances. Highest concentrations (4800-8000 microg/m3) were measured for PBO (inhalable: 290-480 microg). By applying the electro-vaporizer "Nexa Lotte" plug-in mosquito killer concentrations for d-allethrin were in the range of 5-12microg/m3 and 0.5-2 microg/m3 for PBO while with the "Paral" plug-in mosquito killer concentrations of 0.4-5microg/m3 for pyrethrins and 1-7 microg/m3 for PBO were measured. Potential dermal exposures were determined using exposure pads. Between 80 and 1000microg active substance (tetramethrin, phenothrin, cyfluthrin, bioallethrin, pyrethrins, chlorpyrifos) were deposited on the clothing of the total body surface area of the spray user. Highest levels (up to 3000 microg) were determined for PBO. Worst-case uses of the sprays led to 5-9 times higher concentrations. Also a 2-hour stay nearby an operating electro-vaporizer led to a contamination of the clothing (total amounts on the whole body were 450 microg d-allethrin and 50 microg PBO for "Nexa Lotte" plug-in mosquito killer and 80 microg pyrethrins and 190 microg PBO for "Paral" plug-in mosquito killer). Human biomonitoring data revealed urine concentrations of the metabolite (E)-trans-chrysanthemum dicarboxylic acid ((E)-trans-CDCA) between 1.7 microg/l and 7.1 microg/l after 5 minutes of exposure to the different sprays. Also the use of electro-vaporizers led to (E)-trans-CDCA concentrations in the urine in the range of 1.0 microg/l to 6.2 microg/l (1-3 hours exposure period). The exposure data presented can be used for performing human risk assessment when these biocidal products were applied indoors. The airborne concentrations of the non-volatile active chemical compounds could be predicted from first principles using a deterministic exposure model (SprayExpo).

An advanced HPLC-photodiode array detection method for the determination of 12 selected highly polar nitroaromatic compounds in ground water samples of ammunition waste sites has been developed and validated. After solid-phase extraction the limits of detection were in the range 0.1-0.5 microg/l. To prove the applicability of the method to other polar nitroaromatic compounds the retention time of another 32 polar compounds under the specified chromatographic conditions were determined and their UV spectra recorded. To review the method, interlaboratory comparisons were performed with a spiked and a real ground water sample.

Leachate and ground water samples from a trinitrotoluene-contaminated waste disposal site near a former ammunitions plant in Stadtallendorf, Germany, were analyzed by liquid chromatography (LC)-mass spectrometry (MS) and LC-NMR hyphenated techniques to comprehensively characterize the range of highly polar nitroaromatic compounds. Wherever unknown components could not be identified by comparison with a multistandard, the spectroscopic data obtained on-line were used to make initial structure proposals, which were later confirmed by comparison with authentic reference materials. In those cases where reference materials were not commercially available, unknown compounds were isolated by HPLC cuts and their structures were elucidated by off-line NMR and MS investigations. A variety of previously unknown compounds, including nitrophenols, nitrobenzyl alcohols, methylnitrobenzoic acids, and hydroxynitrobenzoic acids, could be identified. The NMR and MS data are presented here. The main polar compounds were additionally quantified.

The objective of our study was to compare three vastly different analytical methods for measuring urinary metabolites of pyrethroid and pyrethrum insecticides to determine whether they could produce comparable data and to determine if similar analytical characteristics of the methods could be obtained by a secondary laboratory. This study was conducted as a part of a series of validation studies undertaken by the German Research Foundation's Committee on the Standardization of Analytical Methods for Occupational and Environmental Medicine. We compared methods using different sample preparation methods (liquid-liquid extraction and solid-phase extraction with and without chemical derivatization) and different analytical detection methods (gas chromatography-mass spectrometry (single quadrupole), gas chromatography-high resolution mass spectrometry (magnetic sector) in both electron impact ionization and negative chemical ionization modes, and high-performance liquid chromatography-tandem mass spectrometry (triple quadrupole) with electrospray ionization). Our cross validation proved that similar analytical characteristics could be obtained with any combination of sample preparation/analytical detection method and that all methods produced comparable analytical results on unknown urine samples.

A new "pre-embarkation" method for aircraft disinsection was investigated using two different 2% d-phenothrin containing aerosols. Five experiments in aircrafts of the type Airbus 310 (4x) and Boeing 747-400 (1x) were performed. In the absence of passengers and crew the d-phenothrin aerosol was sprayed under the seat rows and in a second step at the height of approximately 1.60 m by moving from one end of the cabin to the other. Concentration levels of d-phenothrin were determined at different time periods after application of the aerosol spray. In a B 747-400 with the air conditioning system operating the concentrations ranged between 853 and 1753 microg/m3 during and till 5 min after the beginning of spraying at different locations in the cabin. Within 5-20min after the end of the spraying concentrations of 36-205 microg/m3 and 20-40 min thereafter only ca. 1 microg d-phenothrin/m3 were detectable (average values in relation to each period of measurement). On cabin interior surfaces the median values for mainly horizontal areas ranged from 100 to 1160 ng d-phenothrin/cm2. d-Phenothrin concentrations in the air were sufficient to kill flying insects like house flies and mosquitoes within 20 min. Horizontal surfaces were 100% effective against insects up to 24 h after spraying. Doses inhaled by sprayers determined by personal measurements were calculated to be 30-235 microg d-phenothrin per 100 g spray applied (30% in the respirable fraction for Arrow Aircraft Disinsectant; 10% for Aircraft Disinsectant Denka). If passengers will board, e.g., 20 min after the end of the disinsection operation, inhalation exposure is estimated to be practically negligible. Also possible dermal exposure from residues in seats and headrests is very low for passengers during the flight. Therefore any health effects for passengers and crew members are very unlikely.

Five groundwater samples from the former ammunition production site at Elsnig, Germany, were analyzed for highly polar components by LC-NMR and LC-MS. A variety of unknown pollutants could be identified. Possibilities and limitations of the combined use of LC-NMR and LC-MS techniques for on-line identification are discussed. Further unknown components were identified through isolation by HPLC cuts and off-line NMR and MS investigations. Most of the polar compounds in the investigated samples could also be quantified., (Copyright 2005 John Wiley & Sons, Ltd.)

Exposure measurements were carried out in parked aircrafts during and after application of a biocide aerosol spray (simulated in-flight spraying). The aerosol product SRA spray (Standard Reference Aerosol Spray) was used for spraying. Concentrations of the pyrethrins--the active ingredients--in the air of the passenger cabin (airborne particles, measured during spray application and 40 minutes afterwards) varied from 11 to 65 microg/m3; those of the synergist piperonyl butoxide were 200-485 microg/m3. The concentrations on surfaces of the cabin furniture differed widely. Low concentrations were determined on surfaces in vertical positions (median values: pyrethrins < or =2 ng/cm2; piperonyl butoxide < or =17 ng/cm2), while under seats, on seats and on headrests the concentrations were up to 55.5 ng/cm2 for pyrethrins and 1162.5 ng/cm2 for piperonyl butoxide (median values). The inhaled doses for sprayers (using 100 g of spray) and persons sitting in the passenger cabin were calculated to be 17 microg for pyrethrins and 200 microg for piperonyl butoxide (maximum values). Maximum total external body doses for the applicators during spraying were 830 microg for pyrethrins and 8840 microg for piperonyl butoxide. The potential dermal dose for persons sitting in the passenger cabin was about a factor of two lower.

This report describes our results with transcatheter closure of patent ductus arteriosus between March 1993 and May 2000 including our early experience with the Amplatzer duct occluder. One hundred and sixty-six consecutive procedures were performed in 160 patients. The mean age was 6.8 years (range 0.8 to 26.2), mean weight 24.3 kg (range 7.7 to 84.0). Single or multiple coils were implanted successfully in 114 cases, a Rashind double umbrella in 35 patients, and an Amplatzer duct occluder in 16 patients. After failure to implant coils in one patient, a second attempt with a Rashkind double umbrella was successful. Complete closure of the patent ductus arteriosus was achieved in a total of 148 patients (92.5%), mean fluoroscopy time was 13.7 min (range 3.1 to 126 min). In 144 patients (90.0%), occlusion without residual shunting was achieved by the first interventional approach. Angiography showed immediate closure in 44%, echocardiography within 48 h revealed complete closure in additional 28%. In a further 18%, a residual shunt disappeared spontaneously in the following months. In five patients a second procedure was performed to terminate residual shunting after placement of a Rashkind occluder system by coils. In three patients, the residual shunt resolved. In 12 patients (7.5%) echocardiography showed a residual shunt 2-1259 days after interventional approach. Occlusion rates of the different devices were 83% for the Rashkind occluder, 92% for detachable coils, and 100% for the Amplatzer duct occluder. Coil embolisation into the pulmonary artery occurred in two patients, interventional removal was successful in one of them. There were no further complications. According to our experience interventional occlusion of patent ductus arteriosus is highly effective and associated with a low complication rate. Transcatheter closure using the Amplatzer duct occluder seems to be safe and effective also in small children with a body weight of 8 kg and a large ductus diameter. Compared to the total group of patients, the occlusion rate of the Amplatzer duct occluder was significantly higher (p = 0.005), and of the Rashkind occluder system significantly lower (p = 0.026). Therefore, we recommend the use of detachable coils in patients with small ductus (diameter < or = 2 mm) and the Amplatzer duct occluder in those with a larger ductus. Transcatheter closure of the patent ductus arteriosus according to this regimen should achieve occlusion rates above 95%.

Unlabelled: The purpose of this study was to determine the need, effectiveness and safety of sedation and monitoring in infants and children in a paediatric open low-field MRI system. Of 274 patients (median age 9 y) examined, only 74 children (median age 25 mo) needed sedation. Sedation was achieved by intravenous administration of midazolam (0.2 mg/kg) and etomidate (0.2 mg/kg). Mean total doses required were 0.28 and 0.27 mgl/kg, respectively. With the exception of eight primarily ventilated patients, all children breathed spontaneously. O2 saturation, arterial blood pressure and ECG were monitored. The low resonance frequency of the MRI system required a specially designed high frequency (HF) shielding of the monitor system to avoid HF artifacts. The overall sedation rate was markedly lower (74/274 = 27%) compared to a control group previously examined in a closed high-field MRI system (52/111 = 47%). This was due to a significant lower need for sedation in patients aged up to 10 y (p < or = 0.0001) in the open MRI unit. General anaesthesia could be avoided in all patients. No significant movement artifacts occurred in any of the MRI examinations and no serious side effects were observed., Conclusions: MRI of children is easier in an open MRI system and with fewer sedations, as in closed high-field systems. Sedation by a combination of midazolam and etomidate is highly effective and safe. Monitoring devices for high-field systems may have to be modified for low-field systems. An in-house paediatric MRI unit with an open and special paediatric design is of major advantage for imaging paediatric patients.

Late postoperative arrhythmias are a common problem associated with significant morbidity following Fontan operations. We analyzed in our patients whether age at the time of a modified Fontan procedure (total cavopulmonary connection) has an influence on the frequency of late postoperative arrhythmias. We examined all 66 long-term surviving patients who underwent a total cavopulmonary connection (TCPC) in our center during a nine year period. At the time of TCPC, 31 children were younger (group I) and 35 children were older than 4 years (group II). The follow-up period was almost identical in both groups (group I: 4.29 years, group II: 4.52 years). We evaluated all ecgs performed at maximum intervals of 6 months and all Holter ecgs performed at intervals of 12 months. Atrial tachyarrhythmias (supraventricular tachycardias, atrial flutter) were registered in six patients (9%). All of these patients belonged to group II (17%). Ventricular arrhythmias (couplets, ventricular tachycardia) were found in 3% of the younger and 17% of the older patients. Abnormalities of sinus node function were registered in equal frequency in younger and older children (group I: 35%, group II: 31%), while pauses with a duration of > 2 s where present only in older children (group II: 14%). Pacemaker implantation or antiarrhythmic therapy became necessary in 10/66 patients (15%) affecting none of the children who underwent the TCPC < 4 years (group I) but 10/35 children (group II) who underwent the TCPC at an older age (29%). According to our findings in the medium-term follow-up after TCPC, atrial tachyarrhythmias and complex ventricular arrhythmias are registered less frequently in children who underwent the modified Fontan procedure at an age of less than 4 years. Although further studies will have to show whether these differences persist in the long-term follow-up, these findings represent an additional argument for the elective performance of modified Fontan operations at an age of less than 4 years.

Unlabelled: We describe the results of balloon angioplasty in 5 infants with body weights of 850-2400 g. Three patients with severe aortic valve stenosis and two patients with isthmic coarctation of the aorta experienced relief of stenosis. Two patients with aortic valve stenosis developed thrombosis of the femoral artery; however, complete resolution of the compromised pulse occurred following thrombolytic therapy. In both patients with isthmic coarctation, pulses on the right leg remained diminished. All patients are doing well 0.28 to 3.32 y after the procedure; none has required additional therapy. Our results in a limited number of consecutive low birthweight infants show that balloon dilatation is feasible and can be performed successfully even in neonates with body weights < 1500 g. According to our experience, balloon dilatation in infants with body weights > 2000 g does not differ significantly from standard procedures. In very small infants, however, balloon angioplasty requires special precautions to avoid temperature loss. Arterial access is the major problem in small children, and requires further improvement., Conclusion: Balloon dilatation is feasible even in neonates < 1500 g. However, special precautions to avoid temperature loss are required and arterial access is the major problem.

Objective: To investigate cardiopulmonary performance in patients after a Fontan procedure, comparing it to patients following a Senning operation., Methods: We studied 21 children, with a mean age of 11.1 years, after a total cavopulmonary anastomosis, comparing them to 13 with complete transposition after a Senning procedure, having a mean age of 11.8 years, and 21 control subjects with a mean age of 11.2 years. All were tested on a bicycle ergospirometer., Results: Peak consumption of oxygen, maximal work rate, peak oxygen pulse and endexpiratory pressure of carbon dioxide at a work rate of 1.5 Watt/kg were lowest in patients with a modified Fontan procedure, and highest in the control group (p < or = 0.0278). Production of carbon dioxide, and minute ventilation at a work rate of 1.5 Watt/kg, was highest in the patients after Fontan procedure, and lowest in the healthy subjects (p < or = 0.0163). Production of carbon dioxide per single breath was lower in those having a Fontan procedure (28.9 ml) than in the two other groups (35.1 ml; p = 0.0243). The tidal volume showed no significant differences between the three groups., Conclusions: The reaction to exercise was identical qualitatively in both groups of patients, and comparable to the behaviour of patients with chronic heart failure. Quantitatively, the results of the patients following a Senning procedure lay between those of control subjects and those who had undergone a Fontan operation. The only exception was dead space ventilation, where the patients after a Fontan procedure differed from the two other groups because of their increased ventilation-perfusion mismatch.

The pulmonary sling or aberrant left pulmonary artery has an incidence of 3% to 6% of all anomalies of the aortic arch system. We report a boy with coexistence of a normal and an anomalous left pulmonary artery. Associated congenital anomalies were coarctation, mitral stenosis, and imperforate anus. Cardiac catheterization and angiocardiography at the age of 5 months demonstrated an inconspicuous pulmonary trunk dividing into left and right branches. There was a normal right pulmonary artery, and a main left pulmonary artery supplying the left upper lobe, lingula, and anterior segments of the left lower lobe. In addition, an anomalous left lower lobe artery originated from the proximal right pulmonary artery, passed inferior to the tracheal bifurcation to the left supplying posterior segments of the left lower lobe. Chest X-rays and bronchoscopy could not detect any malformation of the trachea and pulmonary lobulation. There are only three reports of partial anomalous origin of the left pulmonary artery, and only one had a similar course of the accessory artery. This report is the first to present selective angiography and echocardiographic findings of the partial anomalous left pulmonary artery. The development of the partial anomalous pulmonary artery can be explained by the plexiform nature of the primary pulmonary vascular bed and can help to understand the embryology of the pulmonary arteries.

Objective: To compare the amount of furosemide needed to fulfil defined criteria for renal output if given intermittently or as a continuous infusion and to compare the effect of these two regimens on hemodynamic variables and urine electrolyte concentrations., Design: Prospective randomized study of postoperative hemodynamically stable pediatric cardiac patients. The patients were given furosemide according to the urine output, either as an intermittent bolus injection or as a continuous infusion., Setting: Pediatric intensive care unit in a university hospital., Patients: The patients were randomly assigned before admission to either the intermittent i.v. or the continuous furosemide i.v. infusion group., Measurements and Results: Demographic and hemodynamic data were recorded for a maximum of 72 h, as were furosemide dose, urine output, and fluid and inotropic drug requirements. Forty-six patients completed the study. Maximal hourly urine output was significantly higher in the intermittent group. A significantly lower dose of furosemide in the intermittent group produced the same 24-h urine volume as in the continuous infusion group., Conclusions: Intermittent furosemide administration may be recommended in hemodynamically stable postoperative pediatric cardiac patients because of less drug requirement. However, the high maximal urine output may cause hemodynamic problems in patients who depend on high inotropic support.

This is a case report of a boy with a combination of two rare disorders:growth hormone deficiency (GHD) and Wilson disease. To our knowledge, no comparable case has yet been published in the literature. GHD was diagnosed at the age of 4.5 years (height standard deviation score (SDS) -4.85). However, because of a difficult family background, growth hormone (GH) therapy could not be started. The boy was not seen again until the age of 7.7 years (height SDS -4.77), when GHD was reconfirmed and GH therapy could be initiated (dose 0.6 IU/kg/week). At that time, elevated liver enzymes (GPT 128 U/l, GOT 67 U/l, gamma-GT 28 U/l) confused diagnostic procedures. On GH, growth velocity SDS increased from -1.86 to +4.50 in the first year and +3.87 in the second year, and height SDS increased to -4.26 and -3.59. However, serum IGF-I levels did not normalize (max. 67 ng/ml), and liver enzymes were still elevated. At the age of 10 years, Wilson disease was diagnosed in view of low concentration of serum ceruloplasmin, elevated urinary copper excretion and high copper content in a liver biopsy sample. Under a combined therapy with D-penicillamine and GH, serum liver enzymes decreased, and IGF-I levels increased to normal. Height SDS for chronological age has improved constantly.