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  1. Article: The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain.

    Mboma, Olivier / Wirth, Stefan / Aydin, Malik

    Children (Basel, Switzerland)

    2021  Volume 8, Issue 11

    Abstract: Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug (NSAID) and is frequently prescribed to children as an ... ...

    Abstract Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug (NSAID) and is frequently prescribed to children as an analgesic and/or antipyretic. Besides having a well-established safety and efficacy profile when used in appropriate doses, cases of NSAID-induced acute kidney injury (AKI) have been described in the pediatric population, particularly in the context of dehydration and in combination with other drugs. The ingestion of more than 400 mg/kg is associated with severe or life-threatening toxicity. This report is about two previously healthy adolescents, who developed AKI after taking high daily dose of ibuprofen as a pain reliever without any appropriate medical supervision. With these case reports, in addition to the side effect profiles of this analgesic, we would also like to present a certain therapeutic recommendation that we applied in these patients, and furthermore appeal to pediatricians to strictly set the indications for ibuprofen intake.
    Language English
    Publishing date 2021-11-13
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2732685-8
    ISSN 2227-9067
    ISSN 2227-9067
    DOI 10.3390/children8111048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.

    Gorgisen, Gokhan / Aydin, Malik / Mboma, Olivier / Gökyildirim, Mira Y / Chao, Cho-Ming

    International journal of molecular sciences

    2022  Volume 23, Issue 17

    Abstract: Insulin receptor substrates (IRSs) are proteins that are involved in signaling through the insulin receptor (IR) and insulin-like growth factor (IGFR). They can also interact with other receptors including growth factor receptors. Thus, they represent a ... ...

    Abstract Insulin receptor substrates (IRSs) are proteins that are involved in signaling through the insulin receptor (IR) and insulin-like growth factor (IGFR). They can also interact with other receptors including growth factor receptors. Thus, they represent a critical node for the transduction and regulation of multiple signaling pathways in response to extracellular stimuli. In addition, IRSs play a central role in processes such as inflammation, growth, metabolism, and proliferation. Previous studies have highlighted the role of IRS proteins in lung diseases, in particular asthma. Further, the members of the IRS family are the common proteins of the insulin growth factor signaling cascade involved in lung development and disrupted in bronchopulmonary dysplasia (BPD). However, there is no study focusing on the relationship between IRS proteins and BPD yet. Unfortunately, there is still a significant gap in knowledge in this field. Thus, in this review, we aimed to summarize the current knowledge with the major goal of exploring the possible roles of IRS in BPD and asthma to foster new perspectives for further investigations.
    MeSH term(s) Asthma ; Bronchopulmonary Dysplasia ; Humans ; Infant, Newborn ; Insulin/metabolism ; Insulin Receptor Substrate Proteins/metabolism ; Phosphoproteins/metabolism ; Receptor, Insulin/metabolism
    Chemical Substances Insulin ; Insulin Receptor Substrate Proteins ; Phosphoproteins ; Receptor, Insulin (EC 2.7.10.1)
    Language English
    Publishing date 2022-09-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms231710113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Diagnostic Performance of SARS-CoV-2 Rapid Antigen Test in a Large, German Cohort.

    Mboma, Olivier / Rieke, Elmar / Ahmad-Nejad, Parviz / Wirth, Stefan / Aydin, Malik

    Children (Basel, Switzerland)

    2021  Volume 8, Issue 8

    Abstract: We assessed the performance of a rapid antigen test (RAT) in everyday clinical practice. Between 1 November 2020 until 1 April 2021 all in-patients at the Helios University Hospital Wuppertal, Germany, as well as the accompanying relatives at the ... ...

    Abstract We assessed the performance of a rapid antigen test (RAT) in everyday clinical practice. Between 1 November 2020 until 1 April 2021 all in-patients at the Helios University Hospital Wuppertal, Germany, as well as the accompanying relatives at the Children's Hospital received a SARS-CoV-2 RAT and a SARS-CoV-2 RT-PCR prior to admission. Out of 3686 patients, 22 (0.6%) subjects were tested positive by RT-PCR and RAT, and 3591 (97.4%) were negative by both methods, showing discordant results: RT-PCR+/RAT- in 58 (1.6%) and RT-PCR-/RAT+ in 15 patients (0.4%). Overall sensitivity and specificity of RAT was 27.5% (95%CI 18.1-38.6%) and 99.6% (95%CI 99.3-99.8%), respectively. The sensitivity was slightly higher in adults (30.4%, 95%CI 18.8-90.9%) than in pediatric subjects (20.8%, 95%CI 7.1-42.2%). False negative RAT had a statistically higher Ct-value (
    Language English
    Publishing date 2021-08-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2732685-8
    ISSN 2227-9067
    ISSN 2227-9067
    DOI 10.3390/children8080682
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort

    Sallard, Erwan / Schult, Frank / Baehren, Carolin / Buedding, Eleni / Mboma, Olivier / Ahmad-Nejad, Parviz / Ghebremedhin, Beniam / Ehrhardt, Anja / Wirth, Stefan / Aydin, Malik

    Viruses. 2022 Feb. 27, v. 14, no. 3

    2022  

    Abstract: Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are ... ...

    Abstract Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (n = 141). Interestingly, 41% of exacerbated children had a positive test result for human rhinovirus (HRV)/human enterovirus (HEV), and 14% were positive for respiratory syncytial virus (RSV). HRV was particularly prevalent in asthmatics (56%), wheezers (50%), and atopic (66%) patients. Lymphocytes were decreased in asthmatics and in HRV-infected subjects, and patients allergic to house dust mites were more susceptible to HRV infection. Our study thus confirms HRV infection as a strong ‘biomarker’ of exacerbated asthma. Further longitudinal studies will show the clinical progress of those children with a history of an RSV or HRV infection. Vaccination strategies and novel treatment guidelines against HRV are urgently needed to protect those high-risk children from a serious course of disease.
    Keywords Human rhinovirus ; Respiratory syncytial virus ; asthma ; biomarkers ; bronchitis ; dust ; vaccination ; Germany
    Language English
    Dates of publication 2022-0227
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030491
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort.

    Sallard, Erwan / Schult, Frank / Baehren, Carolin / Buedding, Eleni / Mboma, Olivier / Ahmad-Nejad, Parviz / Ghebremedhin, Beniam / Ehrhardt, Anja / Wirth, Stefan / Aydin, Malik

    Viruses

    2022  Volume 14, Issue 3

    Abstract: Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are ... ...

    Abstract Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (
    MeSH term(s) Asthma/epidemiology ; Biomarkers ; Bronchitis ; Child ; Enterovirus ; Enterovirus Infections ; Humans ; Infant ; Picornaviridae Infections ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Virus, Human ; Respiratory Tract Infections/epidemiology ; Rhinovirus ; Virus Diseases ; Viruses
    Chemical Substances Biomarkers
    Language English
    Publishing date 2022-02-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Combined RT-qPCR and pyrosequencing of a Spike glycoprotein polybasic cleavage motif can uncover pediatric SARS-CoV-2 infections associated with heterogeneous presentation.

    Weil, Patrick Philipp / Hentschel, Jacqueline / Schult, Frank / Pembaur, Anton / Ghebremedhin, Beniam / Mboma, Olivier / Heusch, Andreas / Reuter, Anna-Christin / Müller, Daniel / Wirth, Stefan / Aydin, Malik / Jenke, Andreas C W / Postberg, Jan

    Molecular and cellular pediatrics

    2021  Volume 8, Issue 1, Page(s) 4

    Abstract: Background: Reverse transcription of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+)RNA genome and subgenomic RNAs (sgRNAs) and subsequent quantitative polymerase chain reaction (RT-qPCR) is the reliable diagnostic gold standard for ...

    Abstract Background: Reverse transcription of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+)RNA genome and subgenomic RNAs (sgRNAs) and subsequent quantitative polymerase chain reaction (RT-qPCR) is the reliable diagnostic gold standard for COVID-19 diagnosis and the identification of potential spreaders. Apart from clinical relevance and containment, for specific questions, it might be of interest to (re)investigate cases with low SARS-CoV-2 load, where RT-qPCR alone can deliver conflicting results, even though these cases might neither be clinically relevant nor significant for containment measures, because they might probably not be infectious. In order to expand the diagnostic bandwidth for non-routine questions, particularly for the reliable discrimination between negative and false-negative specimens associated with high C
    Results: We successfully established a combined RT-qPCR and S-gene pyrosequencing method which can be optionally exploited after routine diagnostics. This allows a reliable interpretation of RT-qPCR results in specimens with relatively low viral loads and close to the detection limits of qPCR. After laboratory implementation, we tested the combined method in a large pediatric cohort from two German medical centers (n=769). Pyrosequencing after RT-qPCR enabled us to uncover 5 previously unrecognized cases of pediatric SARS-CoV-2-associated diseases, mainly exhibiting mild and heterogeneous presentation-apart from a single case of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, who was hospitalized in the course of the study.
    Conclusions: The proposed protocol allows a specific and sensitive confirmation of SARS-CoV-2 infections close to the detection limits of RT-qPCR. The tested biotinylated primers do not negatively affect the RT-qPCR pipeline and thus can be optionally applied to enable deeper inspection of RT-qPCR results by subsequent pyrosequencing. Moreover, due to the incremental transmission of SARS-CoV-2 variants of concern, we note that the used strategy can uncover (Spike) P681H allowing the pre-selection of SARS-CoV-2 B.1.1.7 candidate specimens for deep sequencing.
    Language English
    Publishing date 2021-04-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2785551-X
    ISSN 2194-7791
    ISSN 2194-7791
    DOI 10.1186/s40348-021-00115-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Combined RT-qPCR and Pyrosequencing of a SARS-CoV-2 Spike Glycoprotein Polybasic Cleavage Motif Uncovers Rare Pediatric COVID-19 Spectrum Diseases of Unusual Presentation

    Weil, Patrick Philipp / Hentschel, Jacqueline / Schult, Frank / Pembaur, Anton / Ghebremedhin, Beniam / Mboma, Olivier / Heusch, Andreas / Reuter, Anna-Christin / Mueller, Daniel / Wirth, Stefan / Aydin, Malik / Jenke, Andreas C. W. / Postberg, Jan

    medRxiv

    Abstract: 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 (+ ...

    Abstract 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.
    Keywords covid19
    Language English
    Publishing date 2020-12-23
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.12.19.20243428
    Database COVID19

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