94 results on '"Stefan Wirth"'
Search Results
2. The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE—an avoidable health risk: the SAFE randomised trial
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Jöran Köchling, Berit Geis, Cho-Ming Chao, Jana-K. Dieks, Stefan Wirth, and Kai O. Hensel
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Perceived alcohol intoxication ,Road safety ,Public health concern ,Alcohol-related road traffic accident ,Driving under the influence ,DUI ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement. Methods In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order. Results 39–53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation. Conclusions Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard. Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS—German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018—Retrospectively registered). Trial protocol can be accessed online.
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- 2021
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3. Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry
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Jan De Laffolie, Antje Ballauff, Stefan Wirth, Carolin Blueml, Frank Risto Rommel, Martin Claßen, Martin Laaß, Thomas Lang, Almuthe Christina Hauer, and the CEDATA-GPGE Study Group
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IBD ,paediarics ,inflammatory bowel disease ,colitis ,Crohn’s disease ,thromboembolism ,Pediatrics ,RJ1-570 - Abstract
ObjectiveAmong patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4–0.9% in hospitalised children with IBD.MethodsCases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung – large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist.ResultsOver 10 years, 4,153 paediatric patients with IBD (0–18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn’s disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56–22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela.ConclusionPaediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.
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- 2022
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4. Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry
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Lotta Elonen, Lena Wölfle, Jan de Laffolie, Carsten Posovszky, the CEDATA–GPGE-Study-Group, Tobias Schwerdt, Rainer Ganschow, Stefan Trenkel, Burkhard Rodeck, Stefan Wirth, Marlen Zurek, Matthias Heiduk, Michael Paulussen, Gunter Flemming, Ekkehard Sturm, Axel Enninger, Söhnke Dammann, Henning Böhme, Michael Melter, Thomas Lang, Philip Bufler, Thomas Lücke, Markus Knuf, Norbert Wagner, Thomas Kaiser, Ralf Pallacks, Andre Hörning, Jens Klinge, Steffen Reinsch, Rüdiger Adam, Stefan Buderus, Markus Richter, Antje Ballauf, Ilse Broekaert, Lars Heerdts, Carolin Blüml, Sabine Peitzsch, Andreas Krahl, Simone Jedwilayties, Maik Heine, Marko Reitmann, Kai Nils Pargac, Jutta Kringel, Anke Dick, Patrick Gerner, Michael Friedt, Enno Iven, Gunter Burmester, Anke Esser, Olaf Raecke, Kerstin Ehrentraut, Esther Schmidt, Jan Däbritz, Stefan Sgoll, Ahlke Willenborg, Sebastian Horn, Ralph Melchior, Rüdiger Kardoff, Martina Kohl-Sobania, Benedikt Pircher, Christoph Ehrsam, Daniela Nolkemper, Adrian Lieb, Almuth Hauer, Markus Prenninger, Martin Laaß, and Dieter Furthner
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IBD ,pediatric ,Crohn's disease ,ulcerative colitis ,Crohn's colitis ,isolated colonic Crohn's ,Pediatrics ,RJ1-570 - Abstract
IntroductionPediatric patients with inflammatory bowel disease (IBD) are classified into Crohn's disease (CD), ulcerative colitis (UC), and unclassifiable (IBD-U). However, data provide evidence that ileal CD (L1) is distinct from colonic CD (L2). The aim of this study was to investigate the clinical features of isolated Crohn's colitis in a pediatric population.Material and MethodsChildren who were prospectively included in the CEDATA–GPGE registry on diagnosis were compared according to the diagnosis of CD with L2 vs. L1 and ileocolonic (L3) involvement pattern as well as IBD-U and UC. The clinical significance of L2 was investigated with regard to extraintestinal manifestations, treatment, surgery, and disease activity.ResultsFifty-two patients with L2 CD at a median age of 13.4 years (±3.8 SD) were compared with 182 L1 (13.8 ± 2.9 SD), 782 with L3 (12.8 ± 3.3 SD), 653 with UC (12.7 ± 3.8 SD), and 111 patients with IBD-U (11.9 ± 4.7 SD). Bloody stools at diagnosis were more common in L2 (44%) than in L1 (19.7%) and L3 (28.8%), but not as common as in UC (66.5%) and IBD-U (61.3%). Fewer CD patients with L2 (10.2%) received exclusive enteral nutrition therapy (EEN) as induction than patients with L1 (34.3%) and L3 (33.3%). After induction therapy, 42.3% of patients with L2 received immunosuppressants and 21% biologicals during follow-up (L1 56.5/10.5%; L3 59/21%; CU 43.5/11.9%; IBD-U 26.1/12.6%). Extraintestinal manifestations were more frequent in L2 (23.1%) vs. L1 (18.7%), L3 (20.2%), CU (15.8%), and IBD-U (11.7%). The number of patients requiring surgery did not differ within the CD subgroups and was significantly lower in UC and IBD-U. Perianal fistula surgery was significantly more common in L2 (44%) than in L1 (4.8%) or L3 (21.7%). In addition, the frequency of surgery for perianal abscesses was also more frequent in L2 (55.6%) than in L1 (12.7%) or L3 (38.4%).ConclusionsThe consideration of pediatric Crohn's colitis as a distinct disease seems necessary as it is characterized by extraintestinal manifestations (EIMs) with mainly joint involvement and perianal fistulas or abscesses requiring surgery and biologic therapy. Thus, colonic Crohn's disease may have an influence on the therapeutic stratification and should be addressed in further studies.
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- 2022
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5. European Society of Emergency Radiology: guideline on radiological polytrauma imaging and service (short version)
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Stefan Wirth, Julian Hebebrand, Raffaella Basilico, Ferco H. Berger, Ana Blanco, Cem Calli, Maureen Dumba, Ulrich Linsenmaier, Fabian Mück, Konraad H. Nieboer, Mariano Scaglione, Marc-André Weber, and Elizabeth Dick
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Europe ,Guideline ,Radiology ,Polytrauma ,Whole-body-CT ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background Although some national recommendations for the role of radiology in a polytrauma service exist, there are no European guidelines to date. Additionally, for many interdisciplinary guidelines, radiology tends to be under-represented. These factors motivated the European Society of Emergency Radiology (ESER) to develop radiologically-centred polytrauma guidelines. Results Evidence-based decisions were made on 68 individual aspects of polytrauma imaging at two ESER consensus conferences. For severely injured patients, whole-body CT (WBCT) has been shown to significantly reduce mortality when compared to targeted, selective CT. However, this advantage must be balanced against the radiation risk of performing more WBCTs, especially in less severely injured patients. For this reason, we recommend a second lower dose WBCT protocol as an alternative in certain clinical scenarios. The ESER Guideline on Radiological Polytrauma Imaging and Service is published in two versions: a full version (download from the ESER homepage, https://www.eser-society.org ) and a short version also covering all recommendations (this article). Conclusions Once a patient has been accurately classified as polytrauma, each institution should be able to choose from at least two WBCT protocols. One protocol should be optimised regarding time and precision, and is already used by most institutions (variant A). The second protocol should be dose reduced and used for clinically stable and oriented patients who nonetheless require a CT because the history suggests possible serious injury (variant B). Reading, interpretation and communication of the report should be structured clinically following the ABCDE format, i.e. diagnose first what kills first.
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- 2020
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6. Efficacy of conservative treatment of perianal abscesses in children and predictors for therapeutic failure
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Lars Boenicke, Johannes Doerner, Stefan Wirth, Hubert Zirngibl, and Mike Ralf Langenbach
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anal fistula ,conservative treatment ,child ,perianal abscess ,recurrence ,Pediatrics ,RJ1-570 - Abstract
Background The optimal management of perianal abscess in children is controversial. Purpose To evaluate the efficiency of conservative treatment of perianal abscess in children and identify parameters that predict therapy failure. Methods All cases of children younger than 14 years of age with perianal abscesses between 2001–2016 were evaluated. Results Of the 113 enrolled patients, 64 underwent subsequent surgery for advanced disease (primary surgery group). Conservative treatment was initiated in 49 patients (primary conservative group) but was stopped because of inefficiency in 25 patients, who were referred for surgery after a median 7.03 days (range, 2 to 16 days). The other 24 patients (48%) initially achieved complete remission after conservative treatment, but 10 were readmitted after a median 34 months (range, 3 to 145 months) with recurrent disease. There were no significant differences in permanent success after conservative treatment between infants (10 of 29, 34%) and older children (4 of 20 [20%], P=0.122). Overall, conservative treatment alone was effective in only 14 of 113 patients. Recurrence after surgery occurred in 16 patients (25%) in the primary surgery group and 11 patients (22%) in the primary conservative group (P=0.75). Univariate analysis of predictors for conservative treatment failure revealed inflammatory values (C-reactive protein and white blood count, P=0.017) and abscess size (P=0.001) as significant parameters, whereas multivariate analysis demonstrated that only abscess size (odds ratio, 3.37; P=0.023) was significant. Conclusion Conservative treatment of perianal abscess is permanently efficient in only a minority of children but is not associated with a higher recurrence rate after subsequent surgery. Abscess size is a predictor for therapy failure.
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- 2020
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7. The Overlooked Microbiome—Considering Archaea and Eukaryotes Using Multiplex Nanopore-16S-/18S-rDNA-Sequencing: A Technical Report Focusing on Nasopharyngeal Microbiomes
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Carolin Baehren, Anton Pembaur, Patrick P. Weil, Nora Wewers, Frank Schult, Stefan Wirth, Jan Postberg, and Malik Aydin
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archaeome ,archaea ,eukaryotes ,PCR ,sequencing ,MinION ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In contrast to bacteria, microbiome analyses often neglect archaea, but also eukaryotes. This is partly because they are difficult to culture due to their demanding growth requirements, or some even have to be classified as uncultured microorganisms. Consequently, little is known about the relevance of archaea in human health and diseases. Contemporary broad availability and spread of next generation sequencing techniques now enable a stronger focus on such microorganisms, whose cultivation is difficult. However, due to the enormous evolutionary distances between bacteria, archaea and eukaryotes, the implementation of sequencing strategies for smaller laboratory scales needs to be refined to achieve as a holistic view on the microbiome as possible. Here, we present a technical approach that enables simultaneous analyses of archaeal, bacterial and eukaryotic microbial communities to study their roles in development and courses of respiratory disorders. We thus applied combinatorial 16S-/18S-rDNA sequencing strategies for sequencing-library preparation. Considering the lower total microbiota density of airway surfaces, when compared with gut microbiota, we optimized the DNA purification workflow from nasopharyngeal swab specimens. As a result, we provide a protocol that allows the efficient combination of bacterial, archaeal, and eukaryotic libraries for nanopore-sequencing using Oxford Nanopore Technologies MinION devices and subsequent phylogenetic analyses. In a pilot study, this workflow allowed the identification of some environmental archaea, which were not correlated with airway microbial communities before. Moreover, we assessed the protocol’s broader applicability using a set of human stool samples. We conclude that the proposed protocol provides a versatile and adaptable tool for combinatorial studies on bacterial, archaeal, and eukaryotic microbiomes on a small laboratory scale.
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- 2023
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8. P-6 SOFOSBUVIR CONTAINING REGIMENS ARE SAFE AND EFFECTIVE IN ADOLESCENTS WITH CHRONIC HEPATITIS C INFECTION
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Stefan Wirth, Regino Gonzalez-Peralta, Philip Rosenthal, Winita Hardikar, Jessica Wen, Maureen M. Jonas, Naveen Mittal, Mary Whitworth, Ronen Arnon, Chuan-Hao Lin, Yury Lobzin, Rene Romero, Vladimir Chulanov, Girish Subbarao, Jeffrey Teckman, Vyacheslav Morozov, Eric Bassetti, Kathryn Kersey, Benedetta Massetto, Yanni Zhu, Polina German, Diana M. Brainard, Sanjay Bansal, Karen F. Murray, Kathleen Schwarz, and William Balistreri
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Specialties of internal medicine ,RC581-951 - Abstract
Background: HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children. Methods: Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses. Results: 150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported. Conclusion: In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.
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- 2021
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9. Microarray-Based Analyses of Rhinovirus Species-Specific Antibody Responses in Exacerbated Pediatric Asthma in a German Pediatric Cohort
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Erwan Sallard, Katarzyna Niespodziana, Maja Bajic, Thomas Schlederer, Peter Errhalt, Ann-Kathrin Behrendt, Stefan Wirth, Almut Meyer-Bahlburg, Anja Ehrhardt, Rudolf Valenta, and Malik Aydin
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rhinovirus ,RV ,virus infection ,asthma ,wheeze ,exacerbation ,Microbiology ,QR1-502 - Abstract
Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite important evidence on the role of RV reported by clinicians and life scientists, there are still unanswered questions regarding their influence on asthma exacerbation in young patients. Thus, we measured the RVspecies-specific IgG titers in our German pediatric exacerbation cohort using a microarray-based technology. For this approach, human sera of patients with exacerbated asthma and wheeze, as well as healthy control subjects (n = 136) were included, and correlation analyses were performed. Concordantly with previously published results, we observed significantly higher cumulative levels of RV species A-specific IgG (p = 0.011) and RV-C-specific IgG (p = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A (p = 0.0011) and species C (p = 0.0009) compared to non-atopic wheezers. Hypothesizing that bacterial infection positively correlates with immune memory against RV, we included nasopharyngeal swab results in our analyses and detected limited correlations. Interestingly, the eosinophil blood titer positively correlated with RV-specific IgG levels. With these observations, we add important observations to the existing data regarding exacerbation in pediatric and adolescent medicine. We propose that scientists and clinicians should pay more attention to the relevance of RV species in susceptible pediatric patients.
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- 2022
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10. The Rhinobiome of Exacerbated Wheezers and Asthmatics: Insights From a German Pediatric Exacerbation Network
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Malik Aydin, Cornelius Weisser, Olivier Rué, Mahendra Mariadassou, Sandra Maaß, Ann-Kathrin Behrendt, Yan Jaszczyszyn, Tatje Heilker, Maximilian Spaeth, Silvia Vogel, Sören Lutz, Parviz Ahmad-Nejad, Viktoria Graf, Aliyah Bellm, Christoph Weisser, Ella A. Naumova, Wolfgang H. Arnold, Anja Ehrhardt, Almut Meyer-Bahlburg, Dörte Becher, Jan Postberg, Beniam Ghebremedhin, and Stefan Wirth
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nasal microbiome ,proteomics ,metagenomics ,bioinformatics ,bacteria ,Moraxella catarrhalis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Although the nose, as a gateway for organism–environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. The aim of this study is to understand the microbiome, the microbial immunology, and the proteome of exacerbated children and adolescents with wheeze and asthma. Considering that a certain proportion of wheezers may show a progression to asthma, the comparison of both groups provides important information regarding clinical and phenotype stratification. Thus, deep nasopharyngeal swab specimens, nasal epithelial spheroid (NAEsp) cultures, and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n = 146), 16 S-rRNA gene amplicon sequencing (n = 64), and proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH, whereas Firmicutes and Bacteroidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs. Moreover, Staphylococcaceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, and Sphingomonadaceae were significantly more abundant in AB compared to WH and HC. The α-diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB, whereby atopic samples of WH were more homogeneous than those of non-atopic subjects. The NAEsp bacterial exposure experiments provided a disrupted epithelial cell integrity, a cytokine release, and cohort-specific proteomic differences especially for Moraxella catarrhalis cultures. This comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
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- 2021
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11. Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4
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Daniel H. Leung, Stefan Wirth, Betty B. Yao, Rolando M. Viani, Regino P. Gonzalez‐Peralta, Maureen M. Jonas, Steven J. Lobritto, Michael R. Narkewicz, Etienne Sokal, Clàudia Fortuny, Evelyn K. Hsu, Antonio Del Valle‐Segarra, Jiuhong Zha, Lois Larsen, Li Liu, Diana L. Shuster, Daniel E. Cohen, and Philip Rosenthal
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.
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- 2018
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12. Do Current Asthma-Preventive Measures Appropriately Face the World Health Organization's Concerns: A Study Presentation of a New Clinical, Prospective, Multicentric Pediatric Asthma Exacerbation Cohort in Germany
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Malik Aydin, Ella A. Naumova, Soeren Lutz, Almut Meyer-Bahlburg, Wolfgang H. Arnold, Florian Kreppel, Anja Ehrhardt, Jan Postberg, and Stefan Wirth
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asthma ,allergy ,childhood ,exacerbation ,epigenome ,biomarker ,Pediatrics ,RJ1-570 - Abstract
In summer 2017, the World Health Organization published 10 facts on asthma, which is known as a major non-communicable disease of high clinical and scientific importance with currently several hundred million people—with many children among them—suffering from air passages inflammation and narrowing. Importantly, the World Health Organization sees asthma as being underdiagnosed and undertreated. Consequently, much more efforts in clinical disease management and research need to be spent on reducing the asthma-related health burden. Particularly, for young approximately 6 months aged patients presenting recurrent bronchitic respiratory symptoms, many parents anxiously ask the doctors for risk prognosis for their children's future life. Therefore, we urgently need to reevaluate if the current diagnostic and treatment measures are in concordance with our yet incomplete knowledge of pathomechanisms on exacerbation. To contribute to this increasing concern worldwide, we established a multicentric pediatric exacerbation study network, still recruiting acute exacerbated asthmatics (children >6 years) and preschool asthmatics/wheezers (children
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- 2020
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13. The Relevance of the Bacterial Microbiome, Archaeome and Mycobiome in Pediatric Asthma and Respiratory Disorders
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Carolin Baehren, Eleni Buedding, Aliyah Bellm, Frank Schult, Anton Pembaur, Stefan Wirth, Anja Ehrhardt, Friedrich Paulsen, Jan Postberg, and Malik Aydin
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microbiome ,archaea ,fungi ,nasopharynx ,oropharynx ,asthma ,Cytology ,QH573-671 - Abstract
Bacteria, as well as eukaryotes, principally fungi, of the upper respiratory tract play key roles in the etiopathogenesis of respiratory diseases, whereas the potential role of archaea remains poorly understood. In this review, we discuss the contribution of all three domains of cellular life to human naso- and oropharyngeal microbiomes, i.e., bacterial microbiota, eukaryotes (mostly fungi), as well as the archaeome and their relation to respiratory and atopic disorders in infancy and adolescence. With this review, we aim to summarize state-of-the-art contributions to the field published in the last decade. In particular, we intend to build bridges between basic and clinical science.
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- 2022
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14. Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort
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Erwan Sallard, Frank Schult, Carolin Baehren, Eleni Buedding, Olivier Mboma, Parviz Ahmad-Nejad, Beniam Ghebremedhin, Anja Ehrhardt, Stefan Wirth, and Malik Aydin
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human rhinovirus ,respiratory syncytial virus ,virus ,infection ,asthma ,bronchitis ,Microbiology ,QR1-502 - 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.
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- 2022
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15. Increased Antibiotic Resistance in Children with Helicobacter pylori Infection: A Retrospective Study
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Luca Helmbold, Beniam Ghebremedhin, Aliyah Bellm, Marc A. Hopkins, Stefan Wirth, and Malik Aydin
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abdominal pain ,children ,multiple drug resistance ,antibiotic resistance ,histopathology ,gastritis ,Medicine - Abstract
Children with recurrent abdominal pain may be suffering from a Helicobacterpylori (HP) infection. The gold standard for confirming HP gastritis is histological evaluation and microbiological tests performed on specimens collected by esophagogastroduodenoscopy (EGD). The aim of this study was to analyze HP positive cultures and antibiograms with regard to clinical and histopathological correlates. The data of 124 subjects with frequent gastrointestinal symptoms who underwent an EGD were retrospectively collected and analyzed. The mean age of the patients was 13 ± 3.6 years. The most frequent complaints were epigastric pain (84%; n = 100/119) and dyspepsia (79%; n = 94/119). HP gastritis was diagnosed in 54% (n = 67). Interestingly, 40% (n = 49) of the isolates were resistant to at least one antibiotic: amoxicillin (20%; n = 10/49), clarithromycin (45%; n = 22/49), or metronidazole (59%; n = 29/49). Isolates were resistant to two or more antibiotics in 16% (n = 20) of cases. In conclusion, we revealed remarkably high resistance rates to amoxicillin, metronidazole, and clarithromycin in our cohort. The presence of antibiotic resistance to more than one antibiotic was substantially increased in our HP-infected patients and this may negatively affect eradication treatment.
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- 2022
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16. Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx
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Kai O. Hensel, Franziska Cantner, Felix Bangert, Stefan Wirth, and Jan Postberg
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Epigenome ,Episome ,Host–pathogen interaction ,Supranucleosomal structure ,X-protein ,HBxAg ,Genetics ,QH426-470 - Abstract
Abstract Background In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. Results To identify virus–host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. Conclusions As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.
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- 2018
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17. The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain
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Olivier Mboma, Stefan Wirth, and Malik Aydin
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ibuprofen ,nonsteroidal anti-inflammatory drugs ,acute kidney injury ,pediatric ,Pediatrics ,RJ1-570 - 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.
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- 2021
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18. The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review
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Malik Aydin, Jana Dietrich, Joana Witt, Maximiliane S. C. Finkbeiner, Jonas J.-H. Park, Stefan Wirth, Christine E. Engeland, Friedrich Paulsen, and Anja Ehrhardt
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ocular surface epithelium ,goblet cells ,nasal epithelium ,3D cell culture ,infection ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
There is a lack of knowledge regarding the connection between the ocular and nasal epithelia. This narrative review focuses on conjunctival, corneal, ultrastructural corneal stroma, and nasal epithelia as well as an introduction into their interconnections. We describe in detail the morphology and physiology of the ocular surface, the nasolacrimal ducts, and the nasal cavity. This knowledge provides a basis for functional studies and the development of relevant cell culture models that can be used to investigate the pathogenesis of diseases related to these complex structures. Moreover, we also provide a state-of-the-art overview regarding the development of 3D culture models, which allow for addressing research questions in models resembling the in vivo situation. In particular, we give an overview of the current developments of corneal 3D and organoid models, as well as 3D cell culture models of epithelia with goblet cells (conjunctiva and nasal cavity). The benefits and shortcomings of these cell culture models are discussed. As examples for pathogens related to ocular and nasal epithelia, we discuss infections caused by adenovirus and measles virus. In addition to pathogens, also external triggers such as allergens can cause rhinoconjunctivitis. These diseases exemplify the interconnections between the ocular surface and nasal epithelia in a molecular and clinical context. With a final translational section on optical coherence tomography (OCT), we provide an overview about the applicability of this technique in basic research and clinical ophthalmology. The techniques presented herein will be instrumental in further elucidating the functional interrelations and crosstalk between ocular and nasal epithelia.
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- 2021
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19. Diagnostic Performance of SARS-CoV-2 Rapid Antigen Test in a Large, German Cohort
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Olivier Mboma, Elmar Rieke, Parviz Ahmad-Nejad, Stefan Wirth, and Malik Aydin
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COVID-19 ,SARS-CoV-2 early diagnosis ,rapid antigen detection test ,primary healthcare center ,Pediatrics ,RJ1-570 - 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 (p < 0.001) compared to true positive values, and overall sensitivity increased to 80% [59.3–93.2%] with Ct value < 30. While the sensitivity of the RAT was poor compared with the RT-PCR, the specificity was excellent. However, the sensitivity increased with lower Ct value, and with the right anamnesis the RAT can be a quick and easy approach to distinguish people who are infectious with SARS-CoV-2 from noninfectious people, enabling appropriate triage in clinical practice while waiting for the RT-PCR result.
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- 2021
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20. Human Species D Adenoviruses Isolated from Diarrheal Feces Show Low Infection Rates in Primary Nasal Epithelial Cells
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Malik Aydin, Sebastian Schellhorn, Stefan Wirth, Wenli Zhang, and Anja Ehrhardt
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adenovirus ,virus ,infection ,nasal epithelial cells ,transduction ,CAR ,Pediatrics ,RJ1-570 - Abstract
The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, rare Ad types 70, 73, and 74 were originally isolated from fecal samples of immunocompromised patients and they represent recombinants of other Ad types. Here we investigated transduction experiments of these reporter gene tagged Ad types in primary cells exemplified by subject-derived primary nasal epithelial cells (NAEPCs). To analyze the transduction rates, we performed flow cytometry, quantitative polymerase chain reaction (PCR), and cytokine analyses 25 h post-infection. We found that, in contrast to Ad type 5 (as a positive control), the transduction rates of NAEPCs with Ad types 70, 73, and 74 were interestingly low. The major Ad receptor (coxsackievirus-adenovirus receptor and CD46) expression levels showed no significant change after infection with Ad types 70, 73 and 74. Moreover, Interleukin 6 (IL-6) was not released after in vitro Ad transduction. Due to the high risk of developing life-threatening complications in immunocompromised patients by these human species D Ads, even more attention needs to be investigated into the development of diagnostic and therapeutic concepts to prevent and treat those opportunistic infections in susceptible patients.
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- 2021
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21. Speckle Tracking Stress Echocardiography Uncovers Early Subclinical Cardiac Involvement in Pediatric Patients with Inflammatory Bowel Diseases
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Kai O. Hensel, Francisca E. Abellan Schneyder, Lucia Wilke, Andreas Heusch, Stefan Wirth, and Andreas C. Jenke
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Medicine ,Science - Abstract
Abstract Inflammatory bowel disease (IBD) is an established risk factor for cardiovascular disease (CVD). However, whether cardiac consequences present early in IBD is unknown. This is the first study in children aiming to unmask altered myocardial mechanics in IBD. We enrolled 50 consecutive normotensive children with Crohn’s disease (CD) (n = 28) or ulcerative colitis (UC) (n = 22). The study groups consisted of 18 patients with active inflammatory disease (mean age 14.6 ± 2.5 years) and 32 children with IBD in remission (14.3 ± 2.3 years). 60 age- and gender-matched children served as healthy controls. Speckle tracking stress echocardiography (STE) was used to assess left ventricular (LV) myocardial strain and strain rate. Circumferential strain rate was significantly decreased in children with active IBD (−1.55 ± 0.26 s−1) and IBD in remission (−1.49 ± 0.26 s−1) versus healthy controls (1.8 ± 0.4 s−1) both at rest (p
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- 2017
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22. From Submerged Cultures to 3D Cell Culture Models: Evolution of Nasal Epithelial Cells in Asthma Research and Virus Infection
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Malik Aydin, Ella A. Naumova, Aliyah Bellm, Ann-Kathrin Behrendt, Federica Giachero, Nora Bahlmann, Wenli Zhang, Stefan Wirth, Friedrich Paulsen, Wolfgang H. Arnold, and Anja Ehrhardt
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epithelial cells ,nasal epithelial cells ,bronchial epithelial cells ,submerged ,3D cell culture ,spheroids ,Microbiology ,QR1-502 - Abstract
Understanding the response to viral infection in the context of respiratory diseases is of significant importance. Recently, there has been more focus on the role of the nasal epithelium in disease modeling. Here, we provide an overview of different submerged, organotypic 3D and spheroid cell culture models of nasal epithelial cells, which were used to study asthma and allergy with a special focus on virus infection. In detail, this review summarizes the importance, benefits, and disadvantages of patient-derived cell culture models of nasal- and bronchial epithelial cells, including a comparison of these cell culture models and a discussion on why investigators should consider using nasal epithelial cells in their research. Exposure experiments, simple virus transduction analyses as well as genetic studies can be performed in these models, which may provide first insights into the complexity of molecular signatures and may open new doors for drug discovery and biomarker research.
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- 2021
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23. House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection
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Malik Aydin, Ella A. Naumova, Friedrich Paulsen, Wenli Zhang, Felix Gopon, Christian Theis, Sören Lutz, Eric Ehrke-Schulz, Wolfgang H. Arnold, Stefan Wirth, and Anja Ehrhardt
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adenovirus ,house dust mite ,CAR ,CD46 ,allergy ,asthma ,Microbiology ,QR1-502 - Abstract
Adenovirus (AdV) infections in the respiratory tract may cause asthma exacerbation and allergic predisposition, and the house dust mite (HDM) may aggravate virus-induced asthma exacerbations. However, the underlying mechanisms of whether and how AdV affects asthmatic patients remains unclear. To address this question, we investigated nasal epithelial cells (NAEPCs) derived from a pediatric exacerbation study cohort for experimental analyses. We analyzed twenty-one different green-fluorescent protein- and luciferase-tagged AdV types in submerged 2D and organotypic 3D cell culture models. Transduction experiments revealed robust transduction of AdV type 5 (AdV5) in NAEPCs, which was associated with an increased uptake of AdV5 in the presence of HDM. In healthy and asthmatic NAEPCs exposed to HDM before infection, we observed a time- and dose-dependent increase of AdV5 uptake associated with upregulation of entry receptors for AdV5. Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma.
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- 2020
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24. CT mapping of the vertebral level of right adrenal vein
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Christoph Degenhart, Hanna Strube, Matthias J. Betz, Anna Pallauf, Martin Bidlingmaier, Evelyn Fischer, Martin Reincke, Maximilian F. Reiser, and Stefan Wirth
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
PURPOSEWe aimed to evaluate the accuracy of multidetector computed tomography (MDCT) venous mapping for the localization of the right adrenal veins (RAV) in patients suffering from primary aldosteronism.METHODSMDCT scans of 75 patients with primary aldosteronism between March 2008 and November 2011 were evaluated by two readers (a junior [R1] and a senior [R2] radiologist) according to the following criteria: quality of RAV depiction (scale, 1–5), localization of the RAV confluence with regard to the inferior vena cava, and depiction of anatomical variants. Results were compared with RAV venograms obtained during adrenal vein sampling and corroborated by laboratory testing of cortisol in selective RAV blood samples. Kappa statistics were calculated for interobserver agreement and for concordance of MDCT mapping with the gold standard.RESULTSSuccessful RAV sampling was achieved in 69 of 75 patients (92%). Using MDCT mapping, adrenal veins could be visualized in 78% (R1, 54/69) and 77% (R2, 53/69) of patients. MDCT mapping led to correct identification of RAV in 70% (R1, 48/69) and 88% (R2, 61/69) of patients. Venograms revealed five cases of anatomical variants, which were correctly identified in 60% (R1, R2). MDCT-based localizations were false or misleading in 16% (R1, 11/69) and 7% (R2, 5/69) of cases.CONCLUSIONPreinterventional MDCT mapping may facilitate successful catheterization in adrenal vein sampling.
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- 2015
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25. Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study
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Kai O. Hensel, Franziska Grimmer, Markus Roskopf, Andreas C. Jenke, Stefan Wirth, and Andreas Heusch
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5±3.1 years and mean disease duration 4.3±3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p=0.019) and circumferential (p=0.016) strain rate both at rest and during exercise (p=0.021). This was more pronounced in T1DM patients with a longer disease duration (p=0.038). T1DM patients with serum HbA1c>9% showed impaired longitudinal (p=0.008) and circumferential strain (p=0.005) and a reduced E/A-ratio (p=0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.
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- 2016
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26. Is loss of fixation following locked plating of proximal humeral fractures related to the number of screws and their positions in the humeral head?
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Mohammad Maddah, Wolf C. Prall, Lucas Geyer, Stefan Wirth, Wolf Mutschler, and Ben Ockert
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proximal humeral fracture, angular stable plating, screw cutout, secondary fracture displacement, loss of fixation ,Orthopedic surgery ,RD701-811 - Abstract
The aim of the study was to examine the correlation between the chosen position of screws and the complications observed in patients who underwent locked plating of proximal humeral fractures. We evaluated radiographs of 367 patients treated by locked-plating for proximal humeral fractures. Radiographs were taken at one day, 6 weeks, 3 months and 6 months after surgery, and were analyzed for secondary fracture displacement, loss of fixation, cutting out of screws and necrosis of the humeral head. Secondary loss of fixation occurred in 58 cases (15.8%) and among those cutting out of screws was observed in 25 cases (6.8%). In cases of secondary loss of fixation a mean of 6.7 screws were used to fix the fracture (vs 6.6, P=0.425). There was neither significant correlation between position of screws and the occurrence of postoperative loss of fixation in Spearman correlation nor relationship from backward logistic regression analysis. Loss of fixation following locked plating of proximal humeral fractures does not relate to the number of screws and their positions in the humeral head. In consequence, anatomic fracture reduction and restoration of the humeral head-shaft angle are still important factors and should not be disregarded.
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- 2014
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27. DNA methylation analysis in the intestinal epithelium-effect of cell separation on gene expression and methylation profile.
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Andreas C Jenke, Jan Postberg, Timothy Raine, Komal M Nayak, Malte Molitor, Stefan Wirth, Arthur Kaser, Miles Parkes, Robert B Heuschkel, Valerie Orth, and Matthias Zilbauer
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Medicine ,Science - Abstract
Epigenetic signatures are highly cell type specific. Separation of distinct cell populations is therefore desirable for all epigenetic studies. However, to date little information is available on whether separation protocols might influence epigenetic and/or gene expression signatures and hence might be less beneficial. We investigated the influence of two frequently used protocols to isolate intestinal epithelium cells (IECs) from 6 healthy individuals.Epithelial cells were isolated from small bowel (i.e. terminal ileum) biopsies using EDTA/DTT and enzymatic release followed by magnetic bead sorting via EPCAM labeled microbeads. Effects on gene/mRNA expression were analyzed using a real time PCR based expression array. DNA methylation was assessed by pyrosequencing of bisulfite converted DNA and methylated DNA immunoprecipitation (MeDIP).While cell purity was >95% using both cell separation approaches, gene expression analysis revealed significantly higher mRNA levels of several inflammatory genes in EDTA/DTT when compared to enzymatically released cells. In contrast, DNA methylation of selected genes was less variable and only revealed subtle differences. Comparison of DNA methylation of the epithelial cell marker EPCAM in unseparated whole biopsy samples with separated epithelium (i.e. EPCAM positive and negative fraction) demonstrated significant differences in DNA methylation between all three tissue fractions indicating cell type specific methylation patterns can be masked in unseparated tissue samples.Taken together, our data highlight the importance of considering the potential effect of cell separation on gene expression as well as DNA methylation signatures. The decision to separate tissue samples will therefore depend on study design and specific separation protocols.
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- 2013
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28. Expression of human beta-defensins in children with chronic inflammatory bowel disease.
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Matthias Zilbauer, Andreas Jenke, Gundula Wenzel, Jan Postberg, Andreas Heusch, Alan D Phillips, Gabriele Noble-Jamieson, Franco Torrente, Camilla Salvestrini, Robert Heuschkel, and Stefan Wirth
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Medicine ,Science - Abstract
BACKGROUND: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children. METHODS: Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn's disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative real-time (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha. RESULTS: Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn's disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon. CONCLUSION: Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD, lending further support for their potential role in disease pathogenesis.
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- 2010
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29. Uncovering the gastrointestinal passage, intestinal epithelial cellular uptake, and AGO2 loading of milk miRNAs in neonates using xenomiRs as tracers
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Patrick Philipp Weil, Susanna Reincke, Christian Alexander Hirsch, Federica Giachero, Malik Aydin, Jonas Scholz, Franziska Jönsson, Claudia Hagedorn, Duc Ninh Nguyen, Thomas Thymann, Anton Pembaur, Valerie Orth, Victoria Wünsche, Ping-Ping Jiang, Stefan Wirth, Andreas C.W. Jenke, Per Torp Sangild, Florian Kreppel, and Jan Postberg
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intestinal maturation ,Nutrition and Dietetics ,necrotizing enterocolitis ,fetal human intestinal epithelial cells ,miRNA target ,Medicine (miscellaneous) ,enteral feeding ,preterm delivery ,preterm piglet - Abstract
Background: Human breast milk has a high microRNA (miRNA) content. It remains unknown whether and how milk miRNAs might affect intestinal gene regulation and homeostasis of the developing microbiome after initiating enteral nutrition. However, this requires that relevant milk miRNA amounts survive the gastrointestinal (GI) passage, are taken up by cells, and become available to the RNA interference machinery. It seems important to dissect the fate of these miRNAs after oral ingestion and GI passage. Objectives: Our goal was to analyze the potential transmissibility of milk miRNAs via the gastrointestinal system in neonate humans and a porcine model in vivo to contribute to the discussion of whether milk miRNAs could influence gene regulation in neonates and thus might vertically transmit developmental relevant signals. Methods: We performed cross-species profiling of miRNAs via deep sequencing and utilized dietary xenobiotic taxon-specific milk miRNA (xenomiRs) as tracers in human and porcine neonates, followed by functional studies in primary human fetal intestinal epithelial cells using adenovirus-type 5-mediated miRNA gene transfer. Results: Mammals share many milk miRNAs yet exhibit taxon-specific miRNA fingerprints. We traced bovine-specific miRNAs from formula nutrition in human preterm stool and 9 d after the onset of enteral feeding in intestinal cells (ICs) of preterm piglets. Thereafter, several xenomiRs accumulated in the ICs. Moreover, a few hours after introducing enteral feeding in preterm piglets with supplemented reporter miRNAs (cel-miR-39-5p/-3p), we observed their enrichment in blood serum and in argonaute RISC catalytic component 2 (AGO2)-immunocomplexes from intestinal biopsies. Conclusions: Milk-derived miRNAs survived GI passage in human and porcine neonates. Bovine-specific miRNAs accumulated in ICs of preterm piglets after enteral feeding with bovine colostrum/formula. In piglets, colostrum supplementation with cel-miR-39-5p/-3p resulted in increased blood concentrations of cel-miR-39-3p and argonaute RISC catalytic component 2 (AGO2) loading in ICs. This suggests the possibility of vertical transmission of miRNA signaling from milk through the neonatal digestive tract. Am J Clin Nutr 2023;xx:xx–xx.
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- 2023
30. P-6 SOFOSBUVIR CONTAINING REGIMENS ARE SAFE AND EFFECTIVE IN ADOLESCENTS WITH CHRONIC HEPATITIS C INFECTION
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Yanni Zhu, Karen F. Murray, Regino P. Gonzalez-Peralta, Vladimir Chulanov, Kathryn Kersey, Chuan-Hao Lin, Philip J. Rosenthal, Naveen Mittal, William F. Balistreri, Kathleen B. Schwarz, Winita Hardikar, Diana M. Brainard, Polina German, Jeffrey Teckman, Benedetta Massetto, Stefan Wirth, Vyacheslav Morozov, Yury Lobzin, Jessica Wen, Mary Whitworth, Maureen M. Jonas, Girish Subbarao, Ronen Arnon, Eric Bassetti, Sanjay Bansal, and Rene Romero
- Subjects
medicine.medical_specialty ,Study drug ,Hepatology ,Sofosbuvir ,business.industry ,Treatment options ,Specialties of internal medicine ,General Medicine ,Discontinuation ,Therapy naive ,Pharmacokinetics ,Chronic hepatitis ,RC581-951 ,Internal medicine ,medicine ,Adverse effect ,business ,medicine.drug - Abstract
Background HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children. Methods Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses. Results 150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported. Conclusion In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.
- Published
- 2021
31. Patients with systemic sclerosis and low CD4 numbers after autologous stem cell transplantation have a favorable outcome
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Ann-Christin Pecher, Reinhild Klein, Ina Koetter, Marieke Wagner, Wichard Vogel, Stefan Wirths, Claudia Lengerke, and Joerg Christoph Henes
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Systemic sclerosis ,Autoimmunity ,Autologous stem cell transplantation ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Treatment with high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (aHSCT) is an intensive treatment option for patients with severe forms of systemic sclerosis (SSc). Even though associated with a high treatment related mortality, the results in this high-risk population are generally favourable. The knowledge on the potential mechanism of action of this therapy and how it can improve patients with SSc is crucial to better select the right patients for aHSCT. Methods This is a monocentric retrospective study from Tübingen, Germany, including 32 patients who underwent aHSCT. Peripheral blood samples were analysed for different lymphocyte subsets at various timepoints before and after aHSCT. Patients were divided into responders and non-responders according to the modified Rodnan skin score and lung function test in the three years following aHSCT. Results Responders showed significantly lower levels of cluster of differentiation (CD)4 positive T cells in the first months after aHSCT (month 1 and 3), B cells (month 3 and 6 after aHSCT) and natural killer cells (month 1). Mantel-cox test showed a significant deviation of the probability curves, i.e. patients with lower CD4 + T cells and natural killer cells one month and B cells after 3 months after stem cell transplantation had a higher probability to belong to the responder group. Conclusions Taken together, this study supports the theory that a profound CD4 + T cell and B cell lymphopenia is important for patients with SSc to achieve a sustained response after aHSCT.
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- 2024
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32. Grape or grain but never the twain? A randomized controlled multiarm matched-triplet crossover trial of beer and wine
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Kai O. Hensel, Jöran Köchling, Berit Geis, and Stefan Wirth
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Adult ,Male ,Alcohol Drinking ,Universities ,Vomiting ,Medicine (miscellaneous) ,Wine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Alcohol intoxication ,0502 economics and business ,Clinical endpoint ,Medicine ,veisalgia ,Humans ,Vitis ,030212 general & internal medicine ,Nutrition and Dietetics ,Cross-Over Studies ,Ethanol ,business.industry ,alcohol ,drunkenness ,05 social sciences ,Ethics committee ,food and beverages ,Beer ,medicine.disease ,Crossover study ,Clinical trial ,Original Research Communications ,Drinking habits ,hangover ,Breath Tests ,050211 marketing ,Female ,business ,Edible Grain ,headache ,Alcoholic Intoxication ,Kater ,Demography ,Breath alcohol concentration - Abstract
Background Alcohol-induced hangover constitutes a significant, yet understudied, global hazard and a large socio-economic burden. Old folk wisdoms such as “Beer before wine and you'll feel fine; wine before beer and you'll feel queer” exist in many languages. However, whether these concepts in fact reduce hangover severity is unclear. Objectives The aim of this study was to investigate the influence of the combination and order of beer and wine consumption on hangover intensity. Methods In this multiarm, parallel randomized controlled matched-triplet crossover open-label interventional trial, participants were matched into triplets and randomly assigned according to age, gender, body composition, alcohol drinking habits, and hangover frequency. Study group 1 consumed beer up to a breath alcohol concentration (BrAC) ≥0.05% and then wine to BrAC ≥0.11% (vice versa for study group 2). Control group subjects consumed either only beer or only wine. On a second intervention day (crossover) ≥1 wk later, study-group subjects were switched to the opposite drinking order. Control-group subjects who drank only beer on the first intervention received only wine on the second study day (and vice versa). Primary endpoint was hangover severity assessed by Acute Hangover Scale rating on the day following each intervention. Secondary endpoints were factors associated with hangover intensity. Results Ninety participants aged 19–40 y (mean age 23.9), 50% female, were included (study group 1 n = 31, study group 2 n = 31, controls n = 28). Neither type nor order of consumed alcoholic beverages significantly affected hangover intensity (P > 0.05). Multivariate regression analyses revealed perceived drunkenness and vomiting as the strongest predictors for hangover intensity. Conclusions Our findings dispel the traditional myths “Grape or grain but never the twain” and “Beer before wine and you'll feel fine; wine before beer and you'll feel queer” regarding moderate-to-severe alcohol intoxication, whereas subjective signs of progressive intoxication were confirmed as accurate predictors of hangover severity. This trial was prospectively registered at the Witten/Herdecke University Ethics Committee as 140/2016 and retrospectively registered at the German Clinical Trials Register as DRKS00015285.
- Published
- 2019
33. Combined RT-qPCR and pyrosequencing of a Spike glycoprotein polybasic cleavage motif can uncover pediatric SARS-CoV-2 infections associated with heterogeneous presentation
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Beniam Ghebremedhin, Andreas Heusch, Daniel Müller, Anton Pembaur, Patrick Philipp Weil, Malik Aydin, Anna-Christin Reuter, Andreas Jenke, Olivier Mboma, Jacqueline Hentschel, Jan Postberg, Frank Schult, and Stefan Wirth
- Subjects
0301 basic medicine ,(+)RNA ,business.industry ,Epidemiology ,Research ,Pediatric SARS-CoV-2-associated diseases ,Gold standard (test) ,Computational biology ,Amplicon ,Reverse transcriptase ,Deep sequencing ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Real-time polymerase chain reaction ,030225 pediatrics ,Pyrosequencing ,Medicine ,business ,Viral load ,COVID-19 surveillance ,Blood sampling - 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 CT values, we combined the RT-qPCR workflow with subsequent pyrosequencing of a S-gene amplicon. This expansion can help to confirm SARS-CoV-2 infections without the demand of confirmative antibody testing, which requires to summon patients again for blood sampling few to several weeks after symptom onset. 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.
- Published
- 2021
34. From Submerged Cultures to 3D Cell Culture Models: Evolution of Nasal Epithelial Cells in Asthma Research and Virus Infection
- Author
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Wolfgang H. Arnold, Ella A. Naumova, Ann-Kathrin Behrendt, Malik Aydin, Stefan Wirth, Anja Ehrhardt, Nora Bahlmann, Friedrich Paulsen, Wenli Zhang, Federica Giachero, and Aliyah Bellm
- Subjects
0301 basic medicine ,Allergy ,submerged ,Cell Culture Techniques ,lcsh:QR1-502 ,Context (language use) ,spheroids ,Disease ,Review ,virus ,Respiratory Mucosa ,Biology ,Virus ,lcsh:Microbiology ,03 medical and health sciences ,3D cell culture ,Transduction (genetics) ,0302 clinical medicine ,Virology ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,bronchial epithelial cells ,nasal epithelial cells ,asthma ,culture techniques ,medicine.disease ,epithelial cells ,Biomarker ,Nasal Mucosa ,030104 developmental biology ,Infectious Diseases ,030228 respiratory system ,Cell culture ,Virus Diseases ,Immunology ,air–liquid-interface - Abstract
Understanding the response to viral infection in the context of respiratory diseases is of significant importance. Recently, there has been more focus on the role of the nasal epithelium in disease modeling. Here, we provide an overview of different submerged, organotypic 3D and spheroid cell culture models of nasal epithelial cells, which were used to study asthma and allergy with a special focus on virus infection. In detail, this review summarizes the importance, benefits, and disadvantages of patient-derived cell culture models of nasal- and bronchial epithelial cells, including a comparison of these cell culture models and a discussion on why investigators should consider using nasal epithelial cells in their research. Exposure experiments, simple virus transduction analyses as well as genetic studies can be performed in these models, which may provide first insights into the complexity of molecular signatures and may open new doors for drug discovery and biomarker research.
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- 2021
35. Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations
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S Ünal, J Koeglmeier, M Meissl, H Ayyıldız Civan, J Melek, T Siahanidou, A M Demir, Patrick Gerner, J H Montoya, Duba H-C., Denise Aldrian, A Koutroumpa, Sahar Mansour, Michael W. Hess, Murat Cakir, Georg F. Vogel, Thomas Müller, J Hornova, T K Frey, Aysel Ünlüsoy Aksu, Y Rachman, Ekkehard Sturm, Andreas R. Janecke, G Düker, M Miqdady, Lukas A. Huber, R Lima, Frank M. Ruemmele, Carsten Posovszky, J Hertecant, Holm H. Uhlig, E Ramos Boluda, Stefan Wirth, Raffi Lev-Tzion, C Deppisch, R Lanzersdorfer, Merit M. Tabbers, Simone Kathemann, Yaron Avitzur, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ARD - Amsterdam Reproduction and Development
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Diarrhea ,0301 basic medicine ,medicine.medical_specialty ,Genetic counseling ,Myosin ,Medizin ,lcsh:Medicine ,Disease ,Myosins ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genotype ,lack of protein ,Medicine ,Enteropathy ,ddc:610 ,tail domain ,Lack of protein ,Cholestasis ,business.industry ,Genotype–phenotype correlation ,lcsh:R ,Progressive familial intrahepatic cholestasis ,General Medicine ,genotype–phenotype correlation ,Tail domain ,medicine.disease ,congenital diarrheal diseases ,Phenotype ,PFIC ,Cholestase ,Transplantation ,Durchfall ,030104 developmental biology ,Parenteral nutrition ,Kontraktile Proteine ,MYO5B ,enteropathy ,YO5B ,030211 gastroenterology & hepatology ,progressive familial intrahepatic cholestasis ,business ,myosin Vbin ,DDC 610 / Medicine & health ,myosin Vb ,microvillus inclusion disease - Abstract
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling., publishedVersion
- Published
- 2021
36. A unique case of 'counting marks' revealed by tomography on a Middle Bronze Age sword from Champagneux (France, Savoie)
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Léonard Dumont, Stefan Wirth, Matthieu N. Boone, Iván Josipovic, Sylvia Lycke, Pieter Tack, Peter Vandenabeele, Guy De Mulder, Universiteit Gent = Ghent University [Belgium] (UGENT), Archéologie, Terre, Histoire, Sociétés [Dijon] (ARTeHiS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Ministère de la Culture et de la Communication (MCC)
- Subjects
Bronze Age ,Archeology ,[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory ,Sword ,counting marks ,metallurgy ,Counting marks ,History and Archaeology ,XRF ,CT-scan ,Craftsmanship ,Chemistry ,Metallurgy ,Middle Bronze Age ,Octagonal-hilted swords ,France ,octagonal-hilted swords - Abstract
In the 1960s, a solid-hilted sword dating to the second half of the Middle Bronze Age (1450–1300 BC) was dredged up in a gravel quarry in the Rhône river at the village of Champagneux (Savoie, France). The sword belongs to the octagonal-hilted swords (German: Achtkantschwerter). This type, mainly found in the northern Alpine region and southern Scandinavia, was until then unknown in France. X-ray fluorescence (XRF) analyses and high-resolution X-ray computed tomography (μCT) of the hilt were carried out to understand how the hilt was cast and fixed to the blade. Thanks to the opportunities offered by these techniques, we were able to reconstruct the chaîne opératoire of this sword with a close inspection of the internal structure of the hilt. Furthermore, we visualised the surface of the sword’s tang located inside the hilt, which shows a series of five vertically arranged marks. Until now, similar symbols were only known on Late Bronze Age bracelets and tools, predominantly in the eastern part of the Alpine region. Although their exact function remains enigmatic, these marks are believed to be markers left by craftsmen on the object during their manufacture. On the solid-hilted sword from Champagneux, these marks could be linked to a way for the craftsman to remember which blade and hilt were supposed to be joined together, shedding light on the organisation of the production process behind this kind of weapon. Dans les années 1960, une épée à poignée métallique datant de la seconde moitié du Bronze moyen (1450–1300 av. J.-C.) fut draguée dans une gravière du Rhône à Champagneux (Savoie). Il s’agit d’une épée à fusée octogonale (en allemand : Achtkantschwert). Ce type, caractéristique de la région nord-Alpine et du sud de la Scandinavie, était jusqu’alors inconnu en France. Des analyses par spectroscopie de fluorescence X (XRF) et tomographie haute résolution par rayons X (μCT) ont été réalisées afin de comprendre comment la poignée a été coulée puis fixée à la lame. Ces méthodes nous ont ainsi permis de reconstituer la chaîne opératoire de cette épée en réalisant une inspection minutieuse de la structure interne de sa poignée. Nous avons par ailleurs été en mesure de visualiser la surface de la languette de la lame, insérée à l’intérieur du manche, qui présente une série de cinq marques disposées verticalement. Des éléments similaires n’étaient jusqu’à présent connus uniquement sur des outils et parures de du Bronze final, essentiellement dans la partie orientale de l’arc alpin. Bien que leur fonction exacte demeure inconnue, ces marques pourraient être des marqueurs laissés sur les objets au moment de leur fabrication. Dans le cas de l’épée de Champagneux, il pourrait s’agir d’un moyen pour l’artisan d’identifier rapidement dans son atelier la lame et la poignée devant être assemblées. Ces marques nous permettent ainsi d’obtenir de nouvelles informations l’organisation de la production de ce type d’arme.
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- 2021
37. Microstructural Integrity of Salvaged Penumbra after Mechanical Thrombectomy
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Maria Berndt, Christian Maegerlein, Fabian Mück, Johannes Kaesmacher, Sebastian Mönch, Tobias Boeckh-Behrens, Claus Zimmer, Stefan Wirth, Silke Wunderlich, and Benjamin Friedrich
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Perfusion scanning ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,X ray computed ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,610 Medicine & health ,Aged ,Retrospective Studies ,Thrombectomy ,Cerebral infarction ,business.industry ,Adult Brain ,Penumbra ,Brain ,Cerebral Infarction ,Thrombolysis ,Middle Aged ,medicine.disease ,Stroke ,Mechanical thrombectomy ,Diffusion Magnetic Resonance Imaging ,Treatment Outcome ,Female ,Neurology (clinical) ,Radiology ,Tomography, X-Ray Computed ,business ,Perfusion ,030217 neurology & neurosurgery - Abstract
BACKGROUND AND PURPOSE: There are sparse data on the microstructural integrity of salvaged penumbral tissue after mechanical thrombectomy of large-vessel occlusions. The aim of the study was to analyze possible microstructural alteration in the penumbra and their association with clinical symptoms as well as angiographic reperfusion success in patients undergoing mechanical thrombectomy. MATERIALS AND METHODS: All patients who underwent mechanical thrombectomy for large-vessel occlusions in the anterior circulation and who received an admission CT perfusion together with postinterventional DTIs were included (n = 65). Angiographic reperfusion success by means of modified Thrombolysis in Cerebral Infarction (mTICI) scale and clinical outcome were recorded. Microstructural integrity was assessed by DTI evaluating the mean diffusivity index within the salvaged gray matter of the former penumbra. RESULTS: The mean diffusivity index was higher in completely recanalized patients (mTICI 3: −0.001 ± 0.034 versus mTICI
- Published
- 2020
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38. Emergency Radiology of the Head and Spine
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Mariano Scaglione, Cem Çalli, Mario Muto, Stefan Wirth, Mariano Scaglione, Cem Çalli, Mario Muto, and Stefan Wirth
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- Emergency medicine--Diagnosis, Medical radiology, Spine--Imaging, Head--Imaging
- Abstract
This book provides an up-to-date, systematic review of all facets of emergency radiology in patients with head and spine injuries. The aim is to equip readers with a detailed knowledge of the various radiological patterns that may be encountered, thereby facilitating prompt diagnosis under circumstances in which time is of crucial importance. The indications, value, and results of the various emergency imaging modalities, including interventional radiology, are described and illustrated in the full range of traumatic and nontraumatic head and spine emergencies. In addition, basic management principles and technological aspects are fully explained, and protocols tailored to the mechanism of injury are presented. Emergency Radiology of the Head and Spine will be of value to neuroradiologists, interventional neuroradiologists, neurosurgeons, emergency radiologists, emergency physicians, radiology residents, radiology technicians, and all physicians and surgeons who work in emergency care.
- Published
- 2022
39. Real-world evidence on tagraxofusp for blastic plasmacytoid dendritic cell neoplasm – collected cases from a single center and case reports
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Philipp Faustmann, Jan C. Schroeder, Lucas Mix, Lennart Harland, Andreas Riedel, Wichard Vogel, Claudia Lengerke, and Stefan Wirths
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BPDCN ,tagraxofusp ,orphan disease ,hematology ,targeted therapy ,first in class therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionBlastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare, aggressive hematologic malignancy. Until recently, the only curative treatment consisted of intensive chemotherapy, followed by hematopoietic cell transplantation (HCT) in eligible adult cases. Tagraxofusp, a CD123-targeted protein-drug conjugate and the first approved targeted treatment for BPDCN, might enhance outcomes especially in patients not eligible for intensive therapies.MethodsHere, we report real-world outcomes of five male patients with a median age of 79 years who received tagraxofusp as first-line treatment for BPDCN.ResultsTagraxofusp was found to be well-tolerated in this elderly cohort, with only one patient requiring discontinuation. Three patients responded to the treatment (two patients achieved a CR and one patient achieved a partial response), of which two subsequently underwent allogeneic (allo) HCT. One patient is alive and well after ≥ 4 years after alloHCT, and one patient shows sustained CR after now 13 cycles of tagraxofusp. The other three patients died of progressive disease 4-11 months after initiation of treatment.DiscussionIn line with results from 13 published cases outside clinical trials in the literature, sustained responses were associated with CR after tagraxofusp treatment and subsequent alloHCT. Our results provide real-world evidence for safety and efficacy of tagraxofusp as first-line treatment for BPDCN.
- Published
- 2024
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40. Bony Impingement Affects Range of Motion after Total Hip Arthroplasty: A Subject-Specific Approach
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Kessler, Oliver, Patil, Shantanu, Stefan, Wirth, Mayr, Eckart, Colwell, Clifford W., Jr., and DʼLima, Darryl D.
- Published
- 2008
- Full Text
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41. Hepatitis B virus infection in children and adolescents
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Marc Bulterys, Geoffrey Dusheiko, Tammy Meyers, Carlo Giaquinto, George K. Siberry, Mei-Hwei Chang, Giuseppe Indolfi, Philippa Easterbrook, Stefan Wirth, Manal H El-Sayed, Nick Walsh, Po-Lin Chan, Martina Penazzato, Maureen M. Jonas, and Claire Thorne
- Subjects
Liver Cirrhosis ,Pediatrics ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Adolescent ,Chronic liver disease ,medicine.disease_cause ,Antiviral Agents ,Hepatology ,Gastroenterology ,Infectious Disease Transmission, Professional-to-Patient ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Seroepidemiologic Studies ,Epidemiology ,medicine ,Humans ,Hepatitis B Vaccines ,Child ,Hepatitis B virus ,Hepatitis B Surface Antigens ,Transmission (medicine) ,business.industry ,Liver Neoplasms ,Alanine Transaminase ,Entecavir ,Hepatitis B ,medicine.disease ,Infectious Disease Transmission, Vertical ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,DNA, Viral ,Practice Guidelines as Topic ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical (mother-to-child) and horizontal early childhood transmission are the main routes of HBV transmission and are responsible for most chronic infections, including among adults who bear the greatest burden of morbidity and mortality. Universal hepatitis B immunisation at birth and in infancy is the key strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections. However, global progress in scale-up of HBV testing and treatment has been slow in adults and children. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HBV infection in adolescents and children, and we highlight key differences from HBV infection in adults. The estimated global prevalence of HBV infection in children aged 5 years or younger is 1·3%. Most children are in the high-replication, low-inflammation phase of infection, with normal or only slightly raised aminotransferases; cirrhosis and hepatocellular carcinoma are rare. Although entecavir is approved and recommended for children aged 2-17 years, and tenofovir for those aged 12-18 years, a conservative approach to treatment initiation in children is recommended. Key actions to address current policy gaps include: validation of non-invasive tests for liver disease staging; additional immunopathogenesis studies in children with HBV infection; long-term follow-up of children on nucleoside or nucleotide analogue regimens to inform guidance on when to start treatment; evaluation of different treatment strategies for children with high rates of HBV replication; and establishment of paediatric treatment registries and international consortia to promote collaborative research.
- Published
- 2019
42. Hepatitis C virus infection in children and adolescents
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Manal H El-Sayed, George K. Siberry, Maureen M. Jonas, Marc Bulterys, Giuseppe Indolfi, Po-Lin Chan, Nick Walsh, Philippa Easterbrook, Carlo Giaquinto, Martina Penazzato, Geoffrey Dusheiko, Stefan Wirth, Mei-Hwei Chang, Claire Thorne, and Tammy Meyers
- Subjects
Ledipasvir ,Liver Cirrhosis ,Pediatrics ,medicine.medical_specialty ,Sofosbuvir ,Adolescent ,Chronic liver disease ,Antiviral Agents ,Hepatology ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,Harm Reduction ,Pregnancy ,Epidemiology ,medicine ,Humans ,Aspartate Aminotransferases ,Pregnancy Complications, Infectious ,Child ,Clinical Trials as Topic ,Hepatitis B Surface Antigens ,business.industry ,Alanine Transaminase ,Glecaprevir ,medicine.disease ,Hepatitis B ,Pibrentasvir ,Infectious Disease Transmission, Vertical ,chemistry ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Elasticity Imaging Techniques ,030211 gastroenterology & hepatology ,Female ,Viral hepatitis ,business ,medicine.drug - Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1-19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1-3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12-17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas.
- Published
- 2019
43. Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx
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Jan Postberg, Franziska Cantner, Kai O. Hensel, Felix Bangert, Stefan Wirth, Hensel, Kai O [0000-0001-5826-6133], Postberg, Jan [0000-0002-8562-3316], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Transcription factories ,viruses ,medicine.disease_cause ,Chromatin fiber loops ,Epigenome ,0302 clinical medicine ,Viral Regulatory and Accessory Proteins ,virus diseases ,cccDNA ,Hep G2 Cells ,Chromatin ,Cell biology ,HBx ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Supranucleosomal structure ,Plasmids ,Chromatin Immunoprecipitation ,Hepatitis B virus ,lcsh:QH426-470 ,X-protein ,Biology ,Cell Line ,03 medical and health sciences ,Protein Domains ,Genetics ,medicine ,Gene silencing ,Humans ,TADs ,Molecular Biology ,Oncogene ,HBxAg ,Cell Nucleus ,Binding Sites ,Sequence Analysis, RNA ,Research ,Circular bacterial chromosome ,Host–pathogen interaction ,digestive system diseases ,lcsh:Genetics ,030104 developmental biology ,Episome ,DNA, Viral ,Hepatocytes ,Trans-Activators ,Nuclear localization sequence - Abstract
Background In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. Results To identify virus–host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. Conclusions As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations. Electronic supplementary material The online version of this article (10.1186/s13072-018-0204-2) contains supplementary material, which is available to authorized users.
- Published
- 2018
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44. Impact of an In-House Pediatric Surgery Unit and Human Milk Centered Enteral Nutrition on Necrotizing Enterocolitis
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Kai O. Hensel, Michael Heldmann, Sonja Zamrik, Federica Giachero, Andreas Jenke, and Stefan Wirth
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Article Subject ,Birth weight ,Medizin ,lcsh:Medicine ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Enteral Nutrition ,0302 clinical medicine ,Enterocolitis, Necrotizing ,030225 pediatrics ,Intensive care ,Pediatric surgery ,Prevalence ,medicine ,Humans ,Infant, Very Low Birth Weight ,030212 general & internal medicine ,Enterocolitis ,Milk, Human ,General Immunology and Microbiology ,business.industry ,Probiotics ,Incidence (epidemiology) ,lcsh:R ,Infant, Newborn ,General Medicine ,medicine.disease ,Intestines ,Low birth weight ,Parenteral nutrition ,Necrotizing enterocolitis ,Female ,Morbidity ,medicine.symptom ,business ,Research Article - Abstract
The importance for mortality and morbidity of an in-house pediatric surgery unit for premature infants with necrotizing enterocolitis (NEC) remains undefined. Data on 389 consecutive very low birth weight infants with a birth weight Conclusions. Short- and possibly also long-term morbidity of NEC is clearly associated with the presence of an on-site pediatric surgery unit. Enteral nutrition with human milk seems to be a strong protective factor against NEC.
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- 2018
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45. Emergency Radiology of the Chest and Cardiovascular System
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Mariano Scaglione, Ulrich Linsenmaier, Gerd Schueller, Ferco Berger, Stefan Wirth, Mariano Scaglione, Ulrich Linsenmaier, Gerd Schueller, Ferco Berger, and Stefan Wirth
- Subjects
- Emergency medical services, Cardiovascular system--Radiography, Chest--Wounds and injuries--Imaging
- Abstract
This book provides an up-to-date, systematic review of all facets of emergency radiology in patients with chest trauma or pain with the aim of equipping the reader with a detailed knowledge of the various radiological patterns, which is essential in order to make a prompt diagnosis under circumstances when time is of critical importance. To this end, the indications, value, and results of the various emergency imaging modalities, including sonography and interventional radiology, are described and illustrated in the full range of blunt chest injuries and nontraumatic chest emergencies. Technological aspects, protocols tailored to the mechanism of injury, and post-processing techniques are also extensively covered. Emergency Radiology of the Chest and Cardiovascular System will be of value to general and interventional radiologists, radiology residents, radiology technicians, and all physicians and surgeons who work in emergency care.
- Published
- 2016
46. Radiological mass casualty incident (MCI) workflow analysis: single-centre data of a mid-scale exercise
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Lucas L. Geyer, Fabian G Mueck, Maximilian Muggenthaler, Uwe Kreimeier, Ulrich Linsenmaier, Karl-Georg Kanz, Stefan Wirth, and Kathrin Wirth
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Time Factors ,Tomography Scanners, X-Ray Computed ,030218 nuclear medicine & medical imaging ,Workflow ,Scan time ,03 medical and health sciences ,0302 clinical medicine ,Workflow analysis ,Medicine ,Humans ,Mass Casualty Incidents ,Radiology, Nuclear Medicine and imaging ,Emergency Radiology Special Feature ,business.industry ,Multiple Trauma ,030208 emergency & critical care medicine ,General Medicine ,Triage ,Service process ,Confidence interval ,Patient Simulation ,Mass-casualty incident ,Single centre ,Radiological weapon ,Nuclear medicine ,business ,Tomography, X-Ray Computed - Abstract
The aim of the study was to analyse and interpret radiological mass casualty incident workflow data.In a mid-scale mass casualty incident exercise, the on-site triage assigned 12 cases to the investigated institution (11 included in the study). Two out of five institutional multislice-CT-scanners were used and the whole CT workflow and radiological service process chain were simulated as close to realistic as possible. The respective time intervals for reaching defined milestones were measured.The average CT in-room time, i.e. from entering to leaving the CT room was 9.43 min [(standard deviation) SD: 2.27 min; 95% (confidence interval) CI: 7.90-10.95 min]. Time spent on CT table was 6.75 min (SD: 1.67; CI: 5.63-7.87), and the pure scan time was 4.22 min (SD: 0.64; CI: 3.79-4.65). The first images after entering the CT room were available at a dedicated CT workstation after 5.85 min (SD: 2.20; CI: 4.37-7.32) and institution wide via picture archiving system (PACS) after 7.85 min (SD: 1.27; CI: 7.00-8.71). However, the PACS archiving process, that is, transfer of standard reconstruction set of CT images into the PACS was finished after 20.85 min (SD: 2.97; CI: 18.85-22.84).Up to six patients may be served per hour and per CT scanner by using a standard whole body CT polytrauma protocol. Dedicated CT triage protocols may even increase this number. The time portion until images were available at end points was relatively long. A solution has to be developed in order to avoid scenarios of patients being faster at end points than their images.
- Published
- 2016
47. Introduction of formula feeding induces subclinical inflammation and altered chromatin structure in the intestine of preterm pigs
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Per T. Sangild, Stefan Wirth, Kai O. Hensel, Rhea Willems, René Liang Shen, Andreas Jenke, Verena Rybicki, Jan Postberg, and Pingping Jiang
- Subjects
Regulation of gene expression ,business.industry ,medicine.disease ,Bioinformatics ,Enteral administration ,digestive system diseases ,Chromatin ,TLR2 ,Parenteral nutrition ,Necrotizing enterocolitis ,Immunology ,Meeting Abstract ,TLR4 ,Medicine ,Interleukin 8 ,business - Abstract
Aim Whereas enteral nutrition has been recognized to play an important role for the development of necrotizing enterocolitis (NEC), the exact pathomechanism is still under debate [1,2]. In this study we aimed to analyze how introduction of enteral foods affects intestinal gene regulation and chromatin structure of different inflammatory and pattern recognition genes (i.e. IL8, TLR2, TLR4, REG3A) in premature pigs before any clinical symptoms of NEC.
- Published
- 2015
48. CT mapping of the vertebral level of right adrenal vein
- Author
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Maximilian F. Reiser, H. Strube, Martin Reincke, Matthias J. Betz, Martin Bidlingmaier, Evelyn Fischer, Anna Pallauf, Stefan Wirth, and Christoph Degenhart
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Concordance ,Vertebral level ,Inferior vena cava ,Young Adult ,Primary aldosteronism ,Interventional Radiology ,Adrenal Glands ,Hyperaldosteronism ,Multidetector Computed Tomography ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Sampling (medicine) ,cardiovascular diseases ,Aged ,Observer Variation ,business.industry ,Gold standard (test) ,Phlebography ,Middle Aged ,medicine.disease ,medicine.vein ,cardiovascular system ,Right adrenal vein ,Female ,Radiology ,Venae Cavae ,Cardiology and Cardiovascular Medicine ,business - Abstract
Purpose We aimed to evaluate the accuracy of multidetector computed tomography (MDCT) venous mapping for the localization of the right adrenal veins (RAV) in patients suffering from primary aldosteronism. Methods MDCT scans of 75 patients with primary aldosteronism between March 2008 and November 2011 were evaluated by two readers (a junior [R1] and a senior [R2] radiologist) according to the following criteria: quality of RAV depiction (scale, 1-5), localization of the RAV confluence with regard to the inferior vena cava, and depiction of anatomical variants. Results were compared with RAV venograms obtained during adrenal vein sampling and corroborated by laboratory testing of cortisol in selective RAV blood samples. Kappa statistics were calculated for interobserver agreement and for concordance of MDCT mapping with the gold standard. Results Successful RAV sampling was achieved in 69 of 75 patients (92%). Using MDCT mapping, adrenal veins could be visualized in 78% (R1, 54/69) and 77% (R2, 53/69) of patients. MDCT mapping led to correct identification of RAV in 70% (R1, 48/69) and 88% (R2, 61/69) of patients. Venograms revealed five cases of anatomical variants, which were correctly identified in 60% (R1, R2). MDCT-based localizations were false or misleading in 16% (R1, 11/69) and 7% (R2, 5/69) of cases. Conclusion Preinterventional MDCT mapping may facilitate successful catheterization in adrenal vein sampling.
- Published
- 2014
49. Fetal response to placental dysfunction leads to 5-hmeC and H2A.Z/H3 acetylation in NOS3 while short-termed mRNA boost entails deferred self-attenuation
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Stefan Wirth, Rhea Willems, Andreas Jenke, Miriam Kanders, Jan Postberg, and Sakeh Forcob
- Subjects
Messenger RNA ,medicine.medical_specialty ,Fetus ,biology ,business.industry ,In vitro ,Cell biology ,body regions ,Endocrinology ,Histone ,Placental dysfunction ,Acetylation ,Internal medicine ,Meeting Abstract ,cardiovascular system ,medicine ,biology.protein ,cardiovascular diseases ,Binding site ,STAT3 ,business - Abstract
Results In human fetuses NOS3 expression directly correlated with 5-hydroxymethylcytosine levels as well as H3K9ac and H2A.Zac at the transcription start site. Using an in vitro model for placental dysfunction we confirmed the dynamic NOS3 response and histone acetylation patterns. Concomitantly we recognized massive turnover of Stat3 at a discrete binding site in the NOS3 promoter upon hypoxic conditions. Moreover, knock-down experiments targeting either STAT3 or NOS3 provided strong evidence for a functional NOS3 and STAT3 relationship. Interestingly, induced hyperacetylation and in vitro reporter assays showed that NOS3 expression becomes self-attenuated by co-expression of intronic 27nt-ncRNA modulating STAT3 signaling.
- Published
- 2014
50. Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms
- Author
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Lucas L. Geyer, Fabian G Mueck, Zsuzsanna Deák, Marcus Treitl, Jochen M. Grimm, Maximilian F. Reiser, and Stefan Wirth
- Subjects
medicine.medical_specialty ,Endoleak ,medicine.medical_treatment ,Contrast Media ,Iterative reconstruction ,Radiation Dosage ,Thoracic aortic aneurysm ,Imaging phantom ,Aortic aneurysm ,Postoperative Complications ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Thrombus ,Aortic Aneurysm, Thoracic ,medicine.diagnostic_test ,Phantoms, Imaging ,business.industry ,Angiography ,Stent ,Thrombosis ,medicine.disease ,Algorithms ,Angiography/methods ,Aortic Aneurysm, Thoracic/radiography ,Aortic Aneurysm, Thoracic/surgery ,Contrast Media/diagnostic use ,Endoleak/etiology ,Endoleak/radiography ,Postoperative Complications/etiology ,Postoperative Complications/radiography ,Radiographic Image Interpretation, Computer-Assisted ,Stents ,Thrombosis/etiology ,Thrombosis/radiography ,Tomography, X-Ray Computed/methods ,Imaging ,Radiology ,Tomography ,Tomography, X-Ray Computed ,business ,Algorithm - Abstract
PURPOSE: To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS: The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS: Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION: Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.
- Published
- 2014
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