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Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC. The aim of this study was to compare RDT performance among different VOCs.This single-centre prospective performance assessment compared RDTs from three manufacturers (NADAL, Panbio, MEDsan) with RT-qPCR including deduced standardized viral load from oropharyngeal swabs for detection of SARS-CoV-2 in a clinical point-of-care setting from November 2020 to January 2022.Among 35 479 RDT/RT-qPCR tandems taken from 26 940 individuals, 164 of the 426 SARS-CoV-2 positive samples tested true positive with an RDT corresponding to an RDT sensitivity of 38.50% (95% CI, 34.00-43.20%), with an overall specificity of 99.67% (95% CI, 99.60-99.72%). RDT sensitivity depended on viral load, with decreasing sensitivity accompanied by descending viral load. VOC-dependent sensitivity assessment showed a sensitivity of 42.86% (95% CI, 32.82-53.52%) for the wild-type SARS-CoV-2, 43.42% (95% CI, 32.86-54.61%) for the Alpha VOC, 37.67% (95% CI, 30.22-45.75%) for the Delta VOC, and 33.67% (95% CI, 25.09-43.49%) for the Omicron VOC. Sensitivity in samples with high viral loads of ≥10RDT sensitivity for detection of the Omicron VOC is reduced in individuals infected with a high viral load, which curtails the effectiveness of RDTs. This aspect furthert: limits the use of RDTs, although RDTs are still an irreplaceable diagnostic tool for rapid, economic point-of-care and extensive SARS-CoV-2 screening.

ZUSAMMENFASSUNGDie Lyme-Arthritis ist die häufigste Spätmanifestation einer Infektion durch Borrelia burgdorferi und manifestiert sich meist als mono- oder oligoartikuläre Arthritis. Serologisch ist sie durch positive IgG-Antikörper und in der Regel negative IgM-Antikörper gegen Borrelien gekennzeichnet. Das Ansprechen auf eine initiale antibiotische Therapie (Doxycyclin oder Amoxicillin) ist in der Regel gut mit Ansprechraten von 80–90 %. Bei etwa 10 % der Patienten entwickelt sich trotz erneuter antibiotischer Therapie eine persistierende Arthritis. Bei diesem postinfektiösen („Antibiotika-refraktären“) Verlauf stehen immunopathologische Mechanismen im Vordergrund. Eine Persistenz nicht lebender Borrelienbestandteile (Peptidoglykane) scheint hierbei die Entzündung zu unterhalten. Entzündungshemmende bzw. immunmodulatorische Therapien können den postinfektiösen Verlauf der Lyme-Arthritis verkürzen. Als weitere Therapieoption kann bei refraktären Verläufen eine arthroskopische Synovektomie erwogen werden.

Background Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. Objective The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. Methods Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. Results As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. Conclusions This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders. International Registered Report Identifier (IRRID) DERR1-10.2196/35774

Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time.In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses (“confirmed exposures”). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest.Most participants were seropositive against the spike antigen; 37% of the participants ≥79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures.Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

BackgroundRapid antigen detection tests (RDT) are an easily accessible, feasible, inexpensive, and point-of-care method in SARS-CoV-2 diagnostics – established in adults as well as in children and adolescents. Despite this, large-scale data of clinical performance in the paediatric population especially regarding the influence of SARS-CoV-2 virus variants of concern (VOC) and COVID-19 vaccination on test accuracy is rare.MethodsThis single-centre prospective diagnostic study evaluates three RDT (NADAL®, Panbio™, MEDsan®) in comparison to quantitative reverse transcription polymerase chain reaction (RT-qPCR). 9,760 oropharyngeal screening samples regarding SARS-CoV-2 VOC and COVID-19 vaccination in paediatric hospitalised patients aged younger than 18 years were enrolled.FindingsRDT sensitivity was 44·7% (157/351, 95% CI 39·6%–50·0%) compared to the reference standard RT-qPCR, specificity 99·8% (9,392/9,409, 95% CI 99·7%–99·9%). Most SARS-CoV-2 infections considered were caused by Omicron VOC. Diagnostic accuracy of RDT depended on specimen containing viral load with a decreasing RDT sensitivity by descending viral load, corresponding with a significantly impaired sensitivity in asymptomatic children. A sensitivity of 71·0% was obtained for a viral load higher than 106SARS-CoV-2 RNA copies per ml suggested as infectivity threshold. No significant differences in RDT sensitivity could be observed regarding gender, symptoms, COVID-19 vaccination status, and VOC.InterpretationIn a paediatric population, RDT have proven to reliably detect potentially highly infectious patients with a viral load of at least 106SARS-CoV-2 RNA copies per ml. Due to the low sensitivity in asymptomatic individuals, the usefulness of RDT seems limited in large-scale SARS-CoV-2 screening programs.FundingFederal Ministry for Education and Science (BMBF), Free State of Bavaria

Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.

Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to

BACKGROUND Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. OBJECTIVE The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. METHODS Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. RESULTS As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. CONCLUSIONS This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/35774

Akute Bauchschmerzen im Kindes- und Jugendalter sind ein häufiger Grund ärztlicher Konsultation. Die Ätiologien der Beschwerden sind vielfältig und oft eine diagnostische Herausforderung für den Kliniker. Komplizierend führen auch extraabdominelle Erkrankungen zum Leitsymptom „Bauchschmerzen“. Wichtig ist die Unterscheidung zwischen akuten Krankheitsbildern, die einer sofortigen diagnostischen oder therapeutischen, ggf. auch chirurgischen Intervention bedürfen und denen, die zunächst beobachtet werden können. Auch müssen lebensbedrohliche Zustände erkannt und rasch behandelt werden. Die Schmerzursachen unterscheiden sich je nach Alter und Vorgeschichte der Patienten erheblich, so kann bspw. ein mechanischer Ileus auf dem Boden unterschiedlichster Erkrankungen entstehen (Yang WC, Chen CY, Wu HP. Etiology of non-traumatic acute abdomen in pediatric emergency departments. World J Clin Cases 2013; 1(9): 276–284). Im vorgestellten Fall soll die Schwierigkeit der ätiologischen Zuordnung eines mechanischen Ileus aufgezeigt werden.

Key Points Question Is continuous SARS-CoV-2 testing accepted by children, parents, and childcare workers and can it prevent viral spreading in day care centers? Findings In this nonrandomized controlled trial, surveillance testing for SARS-CoV-2 among 954 eligible individuals was well accepted by children, parents, and childcare workers if saliva sampling at home was used. Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. Meaning These findings suggest that SARS-CoV-2 surveillance testing is feasible and allows for continued day care attendance for children during the COVID-19 pandemic., This nonrandomized controlled trial investigates the feasibility of SARS-CoV-2 surveillance among children and childcare workers at day care centers in Germany and models the efficacy of surveillance for preventing viral spread., Importance Closure of day care centers has been implemented globally to contain the COVID-19 pandemic but has negative effects on children’s health and psychosocial well-being. Objective To investigate the feasibility of surveillance among children and childcare workers and to model the efficacy of surveillance on viral spread prevention. Design, Setting, and Participants This nonrandomized controlled trial was conducted at 9 day care centers in Wuerzburg, Germany, from October 2020 to March 2021. Participants included children attending day care, childcare workers, and household members. Participating day care centers were assigned to different surveillance modules in a nonrandomized feasibility study. A mathematical model for SARS-CoV-2 spread in day care centers was developed to identify optimal surveillance. Interventions Modules 1, 2, and 3 involved continuous surveillance of asymptomatic children and childcare workers by SARS-CoV-2 polymerase chain reaction testing of either midturbinate nasal swabs twice weekly (module 1) or once weekly (module 2) or self-sampled saliva samples twice weekly (module 3). Module 4 involved symptom-based, on-demand testing of children, childcare workers, and their household members by oropharyngeal swabs. All participants underwent SARS-CoV-2 antibody status testing before and after the sampling period. Questionnaires on attitudes and perception of the pandemic were administered in weeks 1, 6, and 12. Mathematical modeling was used to estimate SARS-CoV-2 spread in day care centers. Main Outcomes and Measures The primary outcomes were acceptance of the respective surveillance protocols (feasibility study) and the estimated number of secondary infections (mathematical modeling). Results Of 954 eligible individuals (772 children and 182 childcare workers), 592 (62%), including 442 children (median [IQR] age, 3 [2-4] years; 214 [48.6%] female) and 150 childcare workers (median [IQR] age, 29 [25-44] years; 129 [90.8%] female) participated in the surveillance. In total, 4755 tests for SARS-CoV-2 detected 2 infections (1 childcare worker and 1 adult household member). Acceptance for continuous surveillance was highest for biweekly saliva testing (150 of 221 eligible individuals [67.9%; 95% CI, 61.5%-73.7%]) compared with biweekly (51 of 117 individuals [43.6%; 95% CI, 35.0%-52.6%]) and weekly (44 of 128 individuals [34.4%; 95% CI, 26.7%-43.0%]) midturbinate swabbing (P

ZusammenfassungHereditäre Störungen der Granulozyten betreffen das angeborene Immunsystem („innate immunity“). Sie lassen sich in Erkrankungen mit quantitativer Reduktion und funktionellen Störungen der Granulozyten/Phagozyten einteilen. Sie können ferner isoliert oder als Begleitsymptom weiterer Störungen auftreten. Pathogenetisch sind Mutationen in so unterschiedlichen Molekülen wie Enzymen, Transkriptionsfaktoren, Adhäsionsproteinen und Strukturproteinen ursächlich beteiligt. Der folgende Übersichtsartikel stellt die Krankheitsbilder schwere kongenitale Neutropenie, zyklische Neutropenie, Shwachman-Diamond-Syndrom, Glykogenose Ib, Chediak-Higashi-Syndrom, Dyskeratosis congenita, Knorpel-Haar-Hypoplasie, Leukozytenadhäsionsdefekte I-III, ß-Actin-Defizienz, RAC-2-Defizienz, spezifischer Granula-Defekt, Glukose-6-Phosphat-Dehydrogenase sowie chronische Granulomatose vor.

Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.

A 9-month-old infant presented with fatal pneumococcal sepsis and attenuated inflammation indices. Even in septic conditions, flow cytometry-based CD62L shedding test on granulocytes proved to be a fast and reliable diagnostic tool for the detection of a defect in the innate immunity. Confirmatory immunologic and genetic assays identified an autosomal-recessive interleukin-1 receptor-associated kinase-4 deficiency due to compound heterozygous mutations.

Als Erzeugnis der lebenden Natur und aufgebaut als organische Masse wird das Holz im Freien durch seine naturlichen Feinde im Laufe der Jahre abgebaut und in seine ursprunglichen Ausgangsstoffe, insbesondere Wasser und Kohlensaure, zerlegt. Bei dieser Veranderung gehen die fur den Baustoff so wichtigen mechanischen Eigenschaften fruhzeitig und weitgehend verloren, so das die Wirtschaft dasjenige Nutzholz besonders schatzt, das durch naturliche Schutzstoffe gegen derartige Zerstorungen bereits in gewissem Umfang gesichert ist. Zu diesen Holzern gehoren besonders das Eichenholz, das Larchenholz und das Kiefernholz, wobei aber darauf hingewiesen werden mus, das der Splint dieser Holzer derartige Stoffe nicht enthalt und daher besonders geschutzt werden mus.

Von der grosen Zahl einheimischer Holzarten werden als Bauholz hauptsachlich die Nadelholzer Fichte, Tanne, Kiefer und Larche sowie die Laubholzer Buche und Eiche verwendet. Als Werkholzer dienen neben den genannten Arten eine grose Zahl von Laubholzern, die sich entweder durch besondere Eigenschaften (Elastizitat, Schlagfestigkeit, Harte u. a.) oder auch durch leichte Bearbeitbarkeit, geringes Quellen und Schwinden auszeichnen.