TY - JOUR A1 - Groeber, Florian A1 - Schober, Lena A1 - Schmid, Freia F. A1 - Traube, Andrea A1 - Kolbus-Hernandez, Silvia A1 - Daton, Karolina A1 - Hoffmann, Sebastian A1 - Petersohn, Dirk A1 - Schaefer-Korting, Monika A1 - Walles, Heike A1 - Mewes, Karsten R. T1 - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II) JF - Toxicology in Vitro N2 - To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus,the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up-validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404. KW - Model KW - Chemicals KW - Assay KW - Episkin KW - Vivo KW - RHE KW - In vitro skin irritation testing KW - Open source reconstructed epidermis KW - Validation KW - Alternative test methods Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187311 VL - 36 ER - TY - THES A1 - Schmid, Andrea T1 - Diagnostische Genauigkeit der Dual-Energy Computertomographie Angiographie bei Patienten mit peripherer arterieller Verschlusskrankheit T1 - Diagnostic Accuracy of Dual-Energy Computertomography Angiography in Patients with Peripheral Arterial Occlusive Disease N2 - Es wurde die diagnostische Genauigkeit fünf verschiedener Rekonstruktionsalgorithmen der DE-CTA der Becken-Bein-Gefäße von Patienten mit pAVK an einem Dual-Source CT mit dem diagnostischen Goldstandard der DSA verglichen. Die DE-CTA zeigte eine exzellente Sensitivität an Becken- und Beingefäßen hinsichtlich einer korrekten Stenosegraduierung, unabhängig von der Rekonstruktion. Die Standard MPR zeigte insgesamt die besten Ergebnisse und ist deshalb vor allem in nicht eindeutigen Fällen die Methode der Wahl. Die Auswertung von DE-CS MPRs, DE-CS MIPs, gekrümmten MPRs oder die semi-automatische quantitative Stenosegradauswertung bringt keinen Zugewinn an diagnostischer Performance im Vergleich zur visuellen Auswertung der Standard MPR. Das Ausmaß der Gefäßwandverkalkungen und die intraluminale Kontrastierung hatten keinen signifikanten Effekt auf die Sensitivität zur Erkennung signifikanter Stenosen an den Becken- und Beingefäßen. Jedoch verschlechterten sich die Spezifität und die Genauigkeit der Rekonstruktionen, welche auf der DE-Knochen- und DE-Plaqueentfernung basieren, signifikant in stark verkalkten oder nur schwach kontrastierten Gefäßsegmenten. Beim Auswerten von DE-CS Rekonstruktionen ist infolgedessen vor allem in schlecht kontrastierten oder stark verkalkten Gefäßen eine weitere Verifizierung des Befundes nötig, um unnötige invasive DSAs als Folge von falsch positiven CTA-Befunden zu reduzieren. N2 - The diagnostic accuracy of five different DE-CTA recontruction approaches of a dual-source CT in patients with peripheral artery disease were compared, using digital subtraction angiography as reference standard. DE-CTA shows an excellent sensitivity for the detection of lower extremity arterial stenosis, regardless of image reconstruction approach. The standard MPR showed the best results overall and is therefore the method of choice in unclear cases. Thus DE-CS MPRs, DE-CS MIPs, curved MPRs and semi-automatic stenosis grading don’t bring additional value regarding the diagnostic performance in comparison to the standard MPR. The amount of vessel wall calcification and the intraluminal contrast had no significant effect on the sensitivity for the detection of lower extremity arterial stenosis. Specifity and accuracy decreased in reconstructions that relied on DE-bone- and DE-plaque-subtraction significantly in vessels with strong calcification or poor contrasting. When analyzing DE-CS reconstructions for poorly contrasted or strongly calcified vessels a further evaluation is necessary, to avoid invasive DSAs as a result of false positive findings. KW - Dual-Source-Computertomographie KW - Periphere arterielle Verschlusskrankheit KW - Computertomographie Angiographie KW - Dual-Source Computertomography KW - Peripheral Artery Disease KW - Computertomography Angiography Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251137 ER - TY - JOUR A1 - Streng, Andrea A1 - Prifert, Christiane A1 - Weissbrich, Benedikt A1 - Sauerbrei, Andreas A1 - Krumbholz, Andi A1 - Schmid-Ott, Ruprecht A1 - Liese, Johannes G. T1 - Similar severity of influenza primary and re-infections in pre-school children requiring outpatient treatment due to febrile acute respiratory illness: prospective, multicentre surveillance study (2013-2015) JF - BMC Infectious Diseases N2 - Background Influenza virus infections in immunologically naïve children (primary infection) may be more severe than in children with re-infections who are already immunologically primed. We compared frequency and severity of influenza virus primary and re-infections in pre-school children requiring outpatient treatment. Methods Influenza-unvaccinated children 1–5 years of age presenting at pediatric practices with febrile acute respiratory infection < 48 h after symptom onset were enrolled in a prospective, cross-sectional, multicenter surveillance study (2013–2015). Influenza types/subtypes were PCR-confirmed from oropharyngeal swabs. Influenza type/subtype-specific IgG antibodies serving as surrogate markers for immunological priming were determined using ELISA/hemagglutination inhibition assays. The acute influenza disease was defined as primary infection/re-infection by the absence/presence of influenza type-specific immunoglobulin G (IgG) and, in a second approach, by the absence/presence of subtype-specific IgG. Socio-demographic and clinical data were also recorded. Results Of 217 influenza infections, 178 were due to influenza A (87 [49%] primary infections, 91 [51%] re-infections) and 39 were due to influenza B (38 [97%] primary infections, one [3%] re-infection). Children with “influenza A primary infections” showed fever with respiratory symptoms for a shorter period than children with “influenza A re-infections” (median 3 vs. 4 days; age-adjusted p = 0.03); other disease characteristics were similar. If primary infections and re-infections were defined based on influenza A subtypes, 122 (87%) primary infections (78 “A(H3N2) primary infections”, 44 “A(H1N1)pdm09 primary infections”) and 18 (13%) re-infections could be classified (14 “A(H3N2) re-infections” and 4 “A(H1N1)pdm09 re-infections”). Per subtype, primary infections and re-infections were of similar disease severity. Children with re-infections defined on the subtype level usually had non-protective IgG titers against the subtype of their acute infection (16 of 18; 89%). Some patients infected by one of the influenza A subtypes showed protective IgG titers (≥ 1:40) against the other influenza A subtype (32/140; 23%). Conclusions Pre-school children with acute influenza A primary infections and re-infections presented with similar frequency in pediatric practices. Contrary to expectation, severity of acute “influenza A primary infections” and “influenza A re-infections” were similar. Most “influenza A re-infections” defined on the type level turned out to be primary infections when defined based on the subtype. On the subtype level, re-infections were rare and of similar disease severity as primary infections of the same subtype. Subtype level re-infections were usually associated with low IgG levels for the specific subtype of the acute infection, suggesting only short-time humoral immunity induced by previous infection by this subtype. Overall, the results indicated recurring influenza virus infections in this age group and no or only limited heterosubtypic antibody-mediated cross-protection. KW - influenza KW - children KW - disease severity KW - IgG KW - immunology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265841 VL - 22 ER - TY - JOUR A1 - Schmid, Andrea A1 - Lois, Anna-Maria A1 - Metz, Corona A1 - Grunz, Jan-Peter A1 - Veldhoen, Simon T1 - Not all that looks fractured is broken - multipartite humeral epicondyles in children JF - European Radiology N2 - Objective Multipartite epicondyles may mimic fractures in the setting of pediatric elbow trauma. This study examines the prevalence of multipartite epicondyles during skeletal development and their association with pediatric elbow fractures. Materials and methods In this retrospective analysis, 4282 elbow radiographs of 1265 elbows of 1210 patients aged 0–17 years were reviewed. The radiographs were analyzed by two radiologists in consensus reading, and the number of visible portions of the medial and lateral epicondyles was noted. For elbows in which epicondylar ossification was not yet visible, the epicondyles were already fused with the humerus or could not be sufficiently evaluated due to projection issues or because osteosynthesis material was excluded. In total, 187 elbows were included for the lateral and 715 for the medial epicondyle analyses. Results No multipartite medial epicondyles were found in patients without history of elbow fracture, whereas 9% of these patients had multipartite lateral epicondyles (p < 0.01). Current or previous elbow fractures increased the prevalence of multipartite epicondyles, with significant lateral predominance (medial epicondyle + 9% vs. lateral + 24%, p < 0.0001). Including all patients regardless of a history of elbow fracture, multipartite medial epicondyles were observed in 3% and multipartite lateral epicondyles in 18% (p < 0.0001). There was no gender difference in the prevalence of multipartition of either epicondyle, regardless of a trauma history. Conclusion Multipartite medial epicondyles occur in patients with current or previous elbow fractures only, whereas multipartite lateral epicondyles may be constitutional. Elbow fractures increase the prevalence of multipartite epicondyles on both sides, with significant lateral predominance. Key Points • Multipartite medial epicondyles should be considered of traumatic origin. • Multipartite lateral epicondyles may be constitutional. • Elbow fractures increase the prevalence of multipartite epicondyles on both sides with lateral predominance. KW - elbow joint KW - epicondyles KW - bone fractures KW - pediatrics KW - radiography Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324987 VL - 32 IS - 8 ER -