ZusammenfassungDer Alpha-1-Antitrypsin-Mangel (AATM) ist mit einer Prävalenz bis zu 1:2000 eine der häufigsten monogenetischen Ursachen für eine Lebertransplantation im Kindesalter. Pulmonal manifestiert sich der AATM erst im Erwachsenenalter. Er wird oft zu spät oder überhaupt nicht diagnostiziert. Die initiale Diagnostik ist mit einer Serumspiegelbestimmung einfach und günstig durchführbar. Bei Werten unter 1,1 g/l sollte eine Genotypisierung erfolgen, die im Alpha-1-Antitrypsin-Zentrum Marburg kostenfrei angeboten wird. Aufgrund des sehr heterogenen Verlaufs sollte die weiterführende Betreuung von Patienten mit AATM jedoch Spezialisten mit ausreichender Erfahrung vorbehalten bleiben. Hierfür eignen sich insbesondere die pädiatrischen Alpha-1-Center. Einen hohen Stellenwert haben die Aufklärung sowie die Aufrechterhaltung einer guten Compliance mit regelmäßigen ärztlichen Verlaufskontrollen, um eine Progredienz der Lebererkrankung zu erfassen. Neben Anamnese und körperlicher Untersuchung sind regelmäßige Blutentnahmen und Ultraschalluntersuchungen (inkl. Leberelastographie) notwendig. Therapeutisch stehen neben einer kurativen Lebertransplantation derzeit lediglich supportive Therapien zur Wahl. Sollte eine Lebertransplantation indiziert sein, ist das Langzeit-Outcome erfreulicherweise sehr gut.

With a prevalence of 1:2000 alpha-1-antitrypsin deficiency (AATD) represents one of the most common monogenetic disorders leading to liver transplantation in children, while a pulmonary affection is not seen before adulthood. However, the diagnosis is often delayed. With the measurement of the alpha-1-antitrypsin serum level the initial diagnosis is easy and cheap. In cases of serum levels below 1.1 g/l genotyping should be performed, which can be done at the alpha-1-antitrypsin center Marburg for free. Because of the complex and heterogeneous course of disease, treatment should be performed by specialized gastroenterologists provided by the pediatric alpha 1-centers. A detailed patient information in order to achieve a good compliance is of great importance to notice a deterioration of liver function as soon as possible. Anamnesis, physical examination, blood tests and abdominal ultrasound (including liver elastography) are needed at least yearly. Liver biopsy plays a minor role for diagnosis and further management. In cases of severe liver disease listing for transplantation needs to be evaluated. The outcome of liver transplantation is reported to be excellent. Besides curative liver transplantation to date only supportive treatments are available.

Background: Surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is essential for the global containment measures with regard to the ongoing pandemic. Diagnostic gold standard is currently reverse transcription of the (+)RNA genome and subgenomic RNAs and subsequent quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs or bronchoalveolar lavages. In order to further improve the diagnostic accuracy, particularly for the reliable discrimination between negative and false-negative specimens, we propose the combination of the RT-qPCR workflow with subsequent pyrosequencing of a S-gene amplicon. This extension might add important value mainly in cases with low SARS-CoV-2 load, where RT-qPCR alone can deliver conflicting results. Results: We successfully established a combined RT-qPCR and S-gene pyrosequencing method. This method can be optionally exploited after routine diagnostics or for epidemiologic studies allowing a more reliable interpretation of conflicting RT-qPCR results. This may occur in specimens with relatively low viral loads and close to the detection limits of qPCR, practically for CT values >30. After laboratory implementation and characterization of a best practice protocol we tested the combined method in a field study on a large pediatric cohort from two German medical centers (n=769). Pyrosequencing after RT-qPCR enabled us to uncover previously unrecognized cases of pediatric COVID-19 spectrum diseases, partially exhibiting unusual and heterogeneous presentation. Moreover, it is notable that in the course of RT-qPCR/pyrosequencing method establishment when routinely confirmed SARS-CoV-2-positive specimens were used we did not observe any case of false-positive diagnosis. Conclusions: The proposed protocol allows a specific and sensitive detection of SARS-CoV-2 close to the detection limits of RT-qPCR. Combined RT-qPCR/pyrosequencing does not negatively affect preceding RT-qPCR pipeline in SARS-CoV-2 diagnostics and can be optionally applied in routine to inspect conflicting RT-qPCR results.

In HBV-infizierten Hepatozyten liegt die HBV DNA als ‚covalently closed circular DNA‘ (cccDNA) episomal im Zellkern vor. Genomische HBV-Integrationen stellen einen potentiellen Pathomechanismus für hepatozelluläre Karzinogenese dar, was wahrscheinlich von epigenetischen Veränderungen durch den Transaktivator HBV X protein (HBx) maßgeblich beeinflusst wird. Bislang ist jedoch noch unklar, welche konkrete Rolle dabei die raumzeitliche Zellkernlokalisation von episomaler cccDNA und HBx sowie deren potentielle Interaktionen mit dem Wirtsgenom spielen.

SummaryChronic HCV infection has been associated with impairment of HRQL in both adults and paediatric patients. Our aim was to assess the HRQL of HCV‐positive children treated with SOF + RBV. The data for this post hoc analysis were collected in a phase 2 open‐label multinational study that evaluated safety and efficacy of SOF (400 mg/day) plus RBV (weight‐based up to 1400 mg/day) for 12 or 24 weeks in adolescents with chronic HCV (GS‐US‐334‐1112). Patients and their parents/guardians completed the PedsQL‐4.0‐SF‐15 questionnaire at baseline, at the end of treatment and in post‐treatment follow‐up. We included 50 adolescents with HCV genotype 2 and 3 without cirrhosis (14.8 ± 1.9 years; male: 58%; treatment‐naïve: 82%; vertically transmitted HCV: 70%). After treatment, 100% of patients with HCV genotype 2 and 95% with genotype 3 achieved SVR‐12. During treatment with SOF + RBV, there were no significant decrements in any of patients’ self‐reported or parent‐proxy‐reported PRO scores regardless of treatment duration (all P > .05). After treatment cessation, we recorded a statistically significant improvement in patients’ self‐reported Social Functioning score by post‐treatment week 12: on average, +4.8 points on a 0‐100 scale (P = .02). By post‐treatment week 24, parent‐proxy‐reported School Functioning score increased by, on average, +13.0 points (P = .0065). In multivariate analysis, history of abdominal pain and psychiatric disorders were predictive of impaired HRQL in adolescents with HCV (P < .05). Adolescents with HCV do not seem to experience any HRQL decrement during treatment with SOF + RBV and experience some improvement of their HRQL scores after achieving SVR.

Background In Germany, 35% of all children are considered to have a "migration background", and in the state of North-Rhine-Westfalia 43%. Frequently, one or both parents of a patient with a migration background have limited German language proficiency. Communication barriers due to a language difference can have a negative impact on quality of care, patient safety and costs of care. In this study, we investigate how children's hospitals are prepared to meet the challenges associated with language barriers. Methods We surveyed all children's hospitals in the state of North-Rhine-Westfalia, Germany. The questionnaire was based on the "Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (CLAS)" and was adapted to circumstances in Germany. Results Thirty-eight hospitals participated (51%) in this survey. Language barriers occurred frequently (75% of respondents mentioned language difficulties in more than 10% of the patient population). 82% of respondents rated their hospital to be "less than well prepared" to overcome language barriers. In the majority of hospitals (62%), the need for an interpreter was determined on a case-to-case basis and not according to any set protocol. In most cases bilingual staff was used for interpreting. However, only 38% of respondents found a list of available bilingual staff to be a sufficient resource. 42% of respondents did not know the monthly costs for professional interpreting services. In the remaining cases, costs were less than € 500/month. Conclusion To overcome language barriers, hospitals rely on local resources. The majority of respondents did not find them to be appropriate and sufficient. The development of quality standards and the provision of financial resources are necessary to mobilize this potential for improvement. Therefore, other disciplines and sectors of healthcare need to be analyzed in order to provide the evidence for a constructive discussion with decision makers in policy and health insurance.

Zusammenfassung Ziel der Studie Der Anteil von Kindern mit Migrationshintergrund unter 5 Jahren liegt bundesweit bei 35%, in Nordrhein-Westfalen (NRW) bei 43%. Häufig sind mit dem Migrationshintergrund unzureichende Deutschkenntnisse bei einem oder beiden Elternteilen verbunden. Kommunikationsbarrieren durch Sprachdifferenzen haben einen negativen Einfluss auf die Behandlungsqualität, Patientensicherheit und Behandlungskosten. Es wird untersucht, wie Kinder- und Jugendkliniken auf die Herausforderung durch Sprachbarrieren vorbereitet sind. Methodik Wir führten eine Querschnittsbefragung aller Kinderkliniken in NRW durch und luden dazu die Klinikdirektoren schriftlich und per email zur Teilnahme ein. Der Fragebogen orientierte sich an den „Standards for Culturally and Linguistically Appropriate Services in Health and Health Care“ (CLAS) und wurde an die deutschen Verhältnisse angepasst. Ergebnisse 38 Kliniken nahmen teil (51%). Sprachbarrieren kommen häufig vor (bei 75% der Antwortenden mehr als 10% der Patienten). 82% der Antwortenden sehen ihre Klinik schlechter als „gut“ auf die Überwindung von Sprachbarrieren vorbereitet. Die Feststellung des Dolmetscherbedarfs erfolgt bei der Mehrheit (61%) „fall-abhängig“ und nicht einem Protokoll folgend. Zur Überwindung von Sprachbarrieren werden überwiegend mehrsprachige Mitarbeiter eingesetzt, wobei nur 38% eine Liste von mehrsprachigen Mitarbeitern als ausreichende Ressource bewerten. Die Kosten, die für professionelle Dolmetscher entstehen, waren 42% der Antwortenden nicht bekannt. In den übrigen Fällen betrugen sie weniger als € 500/Monat. Schlussfolgerung Die Überwindung von Sprachbarrieren erfolgt unter Einsatz lokaler Ressourcen, die aus Sicht der Mehrheit der Antwortenden nicht ausreichen. Die Entwicklung von Qualitätsstandards und Bereitstellung finanzieller Mittel sind notwendig, um das Verbesserungspotenzial zu mobilisieren. Hierfür sind Untersuchungen in anderen Disziplinen und Sektoren notwendig, um in einen Dialog mit Entscheidungsträgern aus Politik und Krankenkassen zu treten.

Cryptorchidism is the most common disorder in paediatric surgery in the Western world and a major risk factor for subfertility and malignancy. In 2009, German national guidelines were changed to recommend that treatment for undescended testes should be completed by the age of 1 instead of 2. However, the share of boys undergoing orchidopexy for cryptorchidism within the first year of life has only marginally increased in response to the guideline of the Association of the Scientific Medical Societies in Germany (AWMF). The number of orchidopexies performed in children below the age of 1 is too low both in Germany as well as internationally. The majority of primary care physicians treating children do not seem to be aware of this discrepancy between guideline recommendations and average actual age at orchidopexy. Moreover, a considerable number of cryptorchidism cases seem to be due to secondary ascent of the testis - an underappreciated condition that usually occurs at school age. Consequently, the timing of orchidopexy in primary undescended testes must be optimised. Therefore, education of parents and primary care physicians regarding the necessity of early orchidopexy and frequent testicular examinations even beyond infancy is mandatory to improve the prognosis of cryptorchidism regarding subfertility and malignancy. Further studies are needed to clarify the reasons for the large number of late orchidopexies.