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Book ; Thesis: Identifikation multiresistenter gramnegativer Keime durch metabolisches Profiling

Kittel, Maximilian / Neumaier, Michael

2019

Institution	Universität Heidelberg
Author's details	vorgelegt von Maximilian Theodor Kittel ; Referent: Prof. Dr. med. Michael Neumaier
Language	German
Size	148 Seiten, Diagramme, 30 cm
Publishing place	Heidelberg
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Dissertation, Ruprecht-Karls-Universität zu Heidelberg, 2020
HBZ-ID	HT020688837
Database	Catalogue ZB MED Medicine, Health

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Article: Heterologous Vector-mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector-Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines.

Gerhards, Catharina / Thiaucourt, Margot / Hetjens, Michael / Haselmann, Verena / Neumaier, Michael / Kittel, Maximilian

Vaccines

2023 Volume 11, Issue 3

Abstract: Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector-vector versus heterologous, vector-mRNA), the ... ...

Abstract	Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector-vector versus heterologous, vector-mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector-vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future.
Language	English
Publishing date	2023-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11030701
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Lightweight Visual Transformers Outperform Convolutional Neural Networks for Gram-Stained Image Classification: An Empirical Study.

Kim, Hee E / Maros, Mate E / Miethke, Thomas / Kittel, Maximilian / Siegel, Fabian / Ganslandt, Thomas

Biomedicines

2023 Volume 11, Issue 5

Abstract: We aimed to automate Gram-stain analysis to speed up the detection of bacterial strains in patients suffering from infections. We performed comparative analyses of visual transformers (VT) using various configurations including model size (small vs. ... ...

Abstract	We aimed to automate Gram-stain analysis to speed up the detection of bacterial strains in patients suffering from infections. We performed comparative analyses of visual transformers (VT) using various configurations including model size (small vs. large), training epochs (1 vs. 100), and quantization schemes (tensor- or channel-wise) using float32 or int8 on publicly available (DIBaS,
Language	English
Publishing date	2023-04-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11051333
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Article: The Impact of Clinical Factors and SARS-CoV-2 Variants on Antibody Production in Vaccinated German Healthcare Professionals Infected Either with the Delta or the Omicron Variant.

Gerhards, Catharina / Steingass, Marlene / Heininger, Alexandra / Lange, Bettina / Hetjens, Michael / Gerigk, Marlis / Neumaier, Michael / Evliyaoglu, Osman / Kittel, Maximilian

Vaccines

2024 Volume 12, Issue 2

Abstract: Background: The aim of the rapid introduction of vaccines during the COVID-19 pandemic was a reduction in SARS-CoV-2 transmission and a less frequent occurrence of severe COVID-19 courses. Thus, we evaluated COVID-19 severity in vaccinated individuals ... ...

Abstract	Background: The aim of the rapid introduction of vaccines during the COVID-19 pandemic was a reduction in SARS-CoV-2 transmission and a less frequent occurrence of severe COVID-19 courses. Thus, we evaluated COVID-19 severity in vaccinated individuals to examine variant-specific symptom characteristics and their clinical impact on the serological immune response. Methods: A total of 185 individuals previously vaccinated against and infected with the SARS-CoV-2 Delta (B.1.617.2) or Omicron (BA.4 and BA.5) variant, were enrolled for anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig level detection. A structured survey regarding medical history was conducted. Results: In 99.5 percent of cases, outpatient treatment was satisfactory. Specific symptoms associated with variants included ageusia and anosmia in patients with Delta infections and throat pain in Omicron infections. Among Delta-infected individuals with specific symptoms, significantly higher levels of anti-N antibodies were observed. Conclusion: Our study identified variant-specific differences in the amount of SARS-CoV-2 antibody production and COVID-19 symptoms. Despite this, vaccinated individuals with Omicron or Delta infections generally experienced mild disease courses. Additionally, asymptomatic individuals exhibit lower anti-SARS-CoV-2 antibody levels, indicating a clinical correlation between disease-specific antibodies and distinct symptoms, particularly in the case of the Delta variant. In follow-up studies, exploring post-COVID syndrome and focusing on cognitive symptoms in the acute phase of Omicron infections is crucial as it has the potential to longitudinally impact the lives of those affected.
Language	English
Publishing date	2024-02-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12020163
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Article ; Online: A case series of severe breakthrough infections observed in nine patients with COVID-19 in a southwestern German university hospital.

Lange, Bettina / Welker, Sybille / Kittel, Maximilian / Jabbour, Claude / Reindl, Wolfgang / Walter, Thomas / Heininger, Alexandra

Infection

2022 Volume 50, Issue 3, Page(s) 775–782

Abstract: Purpose: Vaccination is the key element for protection against COVID-19. Increased vaccination breakthroughs raise the question of whether additional prevention is necessary in case of individual risk factors for a severe course with hospitalization or ... ...

Abstract	Purpose: Vaccination is the key element for protection against COVID-19. Increased vaccination breakthroughs raise the question of whether additional prevention is necessary in case of individual risk factors for a severe course with hospitalization or death despite vaccination. Methods: Since July 13, 2021, there is an extended reporting requirement by German law. We analyzed our hospitalized patients with vaccine breakthrough infection during the first 8 weeks. Results: Nine of 67 patients (13.4%) hospitalized for COVID-19 (median age 75 years) were fully vaccinated. Five of these patients received intensive care; two patients died. All had received two doses of BNT162b2 vaccines (Pfizer-BioNTech). There was a median of 99 days between complete immunization and symptom onset. All patients suffered from ≥ three comorbidities. Six patients (66.7%) showed a negative Anti-SARS-CoV-2-N titer at the time of vaccine breakthrough, five of these also had Anti-SARS-CoV-2-S titers < 100 U/ml. All determinable cases were Delta variant B.1.617.2. Conclusion: Advanced age, underlying cardiorespiratory disease, and the Delta variant of SARS-CoV-2 were associated with hospitalization of our patients, suffering from vaccine breakthrough infection. Avoidance of face masks, lack of immunization of close contacts, and travel to high-risk areas have been observed as modifiable behavioural circumstances. Consistent personal protective measures, vaccination of close caregivers, and increased awareness might be effective measures in addition to COVID-19 booster vaccination for patients at a high risk to suffer a severe course of infection.
MeSH term(s)	Aged ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Communicable Diseases ; Hospitals, University ; Humans ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-03-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-022-01797-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cerebrospinal fluid-related tissue damage in multiple sclerosis patients with iron rim lesions.

Wittayer, Matthias / Weber, Claudia E / Kittel, Maximilian / Platten, Michael / Schirmer, Lucas / Tumani, Hayrettin / Gass, Achim / Eisele, Philipp

Multiple sclerosis (Houndmills, Basingstoke, England)

2023 Volume 29, Issue 4-5, Page(s) 549–558

Abstract: Background: In multiple sclerosis (MS), iron rim lesions (IRLs) are associated with pronounced tissue damage, higher disease severity and have been suggested as an imaging marker of chronic active inflammation behind the blood-brain barrier indicating ... ...

Abstract	Background: In multiple sclerosis (MS), iron rim lesions (IRLs) are associated with pronounced tissue damage, higher disease severity and have been suggested as an imaging marker of chronic active inflammation behind the blood-brain barrier indicating progression. Furthermore, chronic intrathecal compartmentalized inflammation has been suggested to be a mediator of a cerebrospinal fluid (CSF)-related tissue damage. Objective: To investigate CSF markers of intrathecal inflammation in patients with at least one IRL compared to patients without IRLs and to investigate tissue damage in lesions and normal-appearing white matter (NAWM) with proximity to CSF spaces. Methods: A total of 102 patients (51 with at least 1 IRL and 51 age-/sex-matched patients without IRL) scanned with the same 3T magnetic resonance imaging (MRI) and having CSF analysis data were included. Results: Patients with at least one IRL had higher disability scores, higher lesion volumes, lower brain volumes and a higher intrathecal immunoglobulin G (IgG) synthesis. Apparent diffusion coefficient (ADC) values in IRLs were higher compared to non-IRLs. We observed a negative linear correlation of ADC values in all tissue classes and distance to CSF, which was stronger in patients with high IgG quotients. Conclusion: IRLs are associated with higher intrathecal IgG synthesis. CSF-mediated intrathecal smouldering inflammation could explain a CSF-related gradient of tissue damage.
MeSH term(s)	Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/cerebrospinal fluid ; Iron ; Magnetic Resonance Imaging ; Immunoglobulin G ; Inflammation/pathology ; Brain/pathology
Chemical Substances	Iron (E1UOL152H7) ; Immunoglobulin G
Language	English
Publishing date	2023-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/13524585231155639
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Article: Triptychon: Usability evaluation and implementation of a web-based application for patients' lab and vital parameters.

Kittel, Maximilian / Moorthy, Preetha / Rao, Sonika / Halfmann, Marie / Thiaucourt, Margot / Strauß, Maximilian / Haselmann, Verena / Santhanam, Nandhini / Siegel, Fabian / Neumaier, Michael

Digital health

2023 Volume 9, Page(s) 20552076231211552

Abstract: Background: A major challenge in healthcare is the interpretation of the constantly increasing amount of clinical data of interest to inpatients for diagnosis and therapy. It is vital to accurately structure and represent data from different sources to ... ...

Abstract	Background: A major challenge in healthcare is the interpretation of the constantly increasing amount of clinical data of interest to inpatients for diagnosis and therapy. It is vital to accurately structure and represent data from different sources to help clinicians make informed decisions. Objective: We evaluated the usability of our tool 'Triptychon' - a three-part visualisation dashboard of essential patients' medical data provided by a direct overview of their hospitalisation information, laboratory, and vital parameters over time. Methods: The study followed a cohort of 20 participants using the mixed-methods approach, including interviews and the usability questionnaires, Health Information Technology Usability Evaluation Scale (Health-ITUES), and User Experience Questionnaire (UEQ). The participant's interactions with the dashboard were also observed. A thematic analysis approach was applied to analyse qualitative data and the quantitative data's task completion time and success rates. Results: The usability evaluation of the visualisation dashboard revealed issues relating to the terminology used in the user interface and colour coding in its left and middle panels. The Health-ITUES score was 3.72 (standard deviation (SD) = 1.0), and the UEQ score was 1.6 (SD = 0.74). The study demonstrated improvements in intuitive dashboard use and overall satisfaction with using the dashboard daily. Conclusion: The Triptychon dashboard is a promising new tool for medical data presentation. We identified design and layout issues of the dashboard for improving its usability in routine clinical practice. According to users' feedback, the three panels on the dashboard provided a holistic view of a patient's hospital stay.
Language	English
Publishing date	2023-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819396-9
ISSN	2055-2076
ISSN	2055-2076
DOI	10.1177/20552076231211552
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Article ; Online: Humoral SARS-CoV-2 Immune Response in COVID-19 Recovered Vaccinated and Unvaccinated Individuals Related to Post-COVID-Syndrome.

Gerhards, Catharina / Kittel, Maximilian / Ast, Volker / Bugert, Peter / Froelich, Matthias F / Hetjens, Michael / Haselmann, Verena / Neumaier, Michael / Thiaucourt, Margot

Viruses

2023 Volume 15, Issue 2

Abstract: Background: The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline ... ...

Abstract	Background: The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline and the existence of a post-COVID-syndrome (PCS) were addressed. Methods: Forty-nine SARS-CoV-2-qRT-PCR-confirmed participants completed a 12-month examination of anti-SARS-CoV-2-antibody levels and PCS-associated long-term sequelae. Overall, 324 samples were collected. Cell-free DNA (cfDNA) was isolated and quantified from EDTA-plasma. As cfDNA is released into the bloodstream from dying cells, it might provide information on organ damage in the late recovery of COIVD-19. Therefore, we evaluated cfDNA concentrations as a biomarker for a PCS. In the context of antibody dynamics, a random forest-based logistic regression with antibody decline as the target was performed and internally validated. Results: The mean percentage dynamic related to the maximum measured value was 96 (±38)% for anti-RBD/S1 antibodies and 30 (±26)% for anti-N antibodies. Anti-RBD/S1 antibodies decreased in 37%, whereas anti-SARS-CoV-2-anti-N antibodies decreased in 86% of the subjects. Clinical anti-RBD/S1 antibody decline prediction models, including vascular and other diseases, were cross-validated (highest AUC 0.74). Long-term follow-up revealed no significant reduction in PCS prevalence but an increase in cognitive impairment, with no indication for cfDNA as a marker for a PCS. Conclusion: Long-term anti-RBD/S1-antibody positivity was confirmed, and clinical parameters associated with declining titers were presented. A fulminant decrease in anti-SARS-CoV-2-anti-N antibodies was observed (mean change to maximum value 30 (±26)%). Anti-RBD/S1 antibody titers of SARS-CoV-2 recovered subjects boosted with a vaccine exceeded the maximum values measured after single infection by 235 ± 382-fold, with no influence on preexisting PCS. PCS long-term prevalence was 38.6%, with an increase in cognitive impairment compromising the quality of life. Quantified cfDNA measured in the early post-COVID-19 phase might not be an effective marker for PCS identification.
MeSH term(s)	Humans ; Antibodies, Viral ; Cell-Free Nucleic Acids ; Convalescence ; COVID-19/complications ; Immunity, Humoral ; Quality of Life ; SARS-CoV-2 ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome/etiology
Chemical Substances	Antibodies, Viral ; Cell-Free Nucleic Acids ; COVID-19 Vaccines
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15020454
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Effectiveness of Safety Interventions in Fire Engines to Reduce Potential Airborne Transmission of SARS-CoV-2

Bourdon, Elmar / Schaefer, Thomas / Kittel, Maximilian / Raedle, Matthias / Heininger, Alexandra

Fire. 2021 Dec. 19, v. 4, no. 4

2021

Abstract: Physical distancing and wearing a face mask are key interventions to prevent COVID-19. While this remains difficult to practice for millions of firefighters in fire engines responding to emergencies, the delayed forthcoming of evidence on the ... ...

Abstract	Physical distancing and wearing a face mask are key interventions to prevent COVID-19. While this remains difficult to practice for millions of firefighters in fire engines responding to emergencies, the delayed forthcoming of evidence on the effectiveness of such safety interventions in this setting presents a major problem. In this field experimental study, we provided initial evidence to close this gap. We examined total aerosol burden in the cabin of a fire engine whilst manipulating crew size, use of FFP2 respirators and use of SCBA full-face masks during 15-min driving periods. At the same time, we controlled for crew activity and speaking, vehicle speed, cabin ventilation, cabin air temperature, pressure and humidity. Limiting the crew size, using FFP2 respirators and not donning SCBA full-face masks was associated with a reduction of the arithmetic mean of total aerosol burden of up to 49%. This study provided initial evidence on the effectiveness of safety interventions in fire engines to reduce potential airborne transmission of SARS-CoV-2 through aerosols. More research about the physical and the clinical effectiveness of such safety interventions is needed.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; aerosols ; air temperature ; airborne transmission ; face masks ; humidity
Language	English
Dates of publication	2021-1219
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ISSN	2571-6255
DOI	10.3390/fire4040098
Database	NAL-Catalogue (AGRICOLA)

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Article: Results of a European-Wide External Quality Assessment (EQA) Scheme for Serological Detection of Anti-SARS-CoV-2 (CoVimm)—Pitfalls of Routine Application

Kittel, Maximilian / Eichner, Romy / Aida, Sihem / Bode, Anna / Ast, Volker / Kessler, Anja / Neumaier, Michael / Wölfel, Roman / Haselmann, Verena

Viruses. 2022 July 28, v. 14, no. 8

2022

Abstract: Background: During the last two years, a variety of assays for the serological detection of antibodies to the new SARS-CoV-2 virus have been launched and used as part of standard care in many laboratories. The pace with which these tests have been ... ...

Abstract	Background: During the last two years, a variety of assays for the serological detection of antibodies to the new SARS-CoV-2 virus have been launched and used as part of standard care in many laboratories. The pace with which these tests have been introduced into routine care emphasizes the importance of quality measures for analytical methods, particularly with regard to the implications of results for clinical and epidemiologic decisions. Accuracy, reliability and comparability of analytical test results are thus essential, and here external quality assessment (EQA) is the most important quality assurance tool. It allows us to achieve harmonization of test methods as a prerequisite for a high standard of performance for laboratory and analytical techniques and their interpretation. Methods: This EQA scheme consisted of pre-characterized clinical biospecimens dedicated to the analysis of anti-SARS-CoV-2 IgG total antibodies and differentiation into spike protein-specific IgG antibodies against SARS-CoV-2 (anti-S-SARS-CoV-2) and nucleocapsid-specific IgG antibodies against SARS-CoV-2 (anti-N-SARS-CoV-2). Results: A total of 239 laboratories across Europe participated in this scheme, called CoVimm. In detail, 536 results for anti-SARS-CoV-2 IgG, 431 results for anti-S-SARS-CoV-2 IgG, and 200 results for anti-N-SARS-CoV-2 IgG were reported. Based on the pre-defined thresholds, the success rates for the determination of anti-S-SARS-CoV-2 IgG and anti-N-SARS-CoV-2 IgG were 96% and 90%, respectively. Interestingly, only 64% of the participating laboratories successfully passed the EQA scheme for the determination of total anti-SARS-CoV-2 IgG. Conclusions: This EQA revealed serious concerns regarding the reliability and appropriate use of anti-SARS-CoV-2 antibody assays in routine care. In addition to the wide heterogeneity of different assays used by participating laboratories, a lack of standardization and harmonization is also evident. This is of particular importance for reliable and clinically meaningful interpretation of test results.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; antibodies ; quality control ; viruses ; Europe
Language	English
Dates of publication	2022-0728
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081662
Database	NAL-Catalogue (AGRICOLA)

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