Publikationen im NUM
Hier finden Sie eine Liste der Publikationen, die im Zusammenhang mit dem Netzwerk Universitätsmedizin in der ersten und zweiten Förderphase entstanden sind.
U. Ebong,
S. Büttner,
S. Schmidt,
F. Flack,
P. Korf,
L. Peters,
B. Grüner,
S. Stenger,
T. Stamminger,
H. Kestler,
M. Beer and
C. Kloth,
"Quantitative Evaluation of COVID-19 Pneumonia CT Using AI Analysis—Feasibility and Differentiation from Other Common Pneumonia Forms",
Diagnostics (Basel),
vol. 13,
no. 12,
pp. 2129,
2023.
| DOI: | 10.3390/diagnostics13122129 |
D. Wolf,
T. Payer,
C. Lisson,
C. Lisson,
M. Beer,
M. Götz and
T. Ropinski,
"Self-Supervised Pre-Training with Contrastive and Masked Autoencoder Methods for Dealing with Small Datasets in Deep Learning for Medical Imaging",
Sci Rep,
vol. 13,
pp. 46433,
2023.
[en]
C. Thibeault,
L. Bardtke,
K. Vanshylla,
V. Cristanziano,
K. A. Eberhardt,
P. Stubbemann,
D. Hillus,
P. Tober-Lau,
P. Mukherjee,
F. Münn,
L. J. Lippert,
E. T. Helbig,
T. Lingscheid,
F. Steinbeis,
M. Mittermaier,
M. Witzenrath,
T. Zoller,
P. Group,
F. Klein,
L. E. Sander and
F. Kurth,
"Short- and long-term T cell and antibody responses following
dexamethasone treatment in COVID-19",
JCI Insight,
vol. 8,
no. 8,
Apr.
2023.
Abstract:
BACKGROUNDAfter its introduction as standard-of-care for severe COVID-19, dexamethasone has been administered to a large number of patients globally. Detailed knowledge of its impact on the cellular and humoral immune response to SARS-CoV-2 remains scarce.METHODSWe included immunocompetent individuals with (a) mild COVID-19, (b) severe COVID-19 before introduction of dexamethasone treatment, and (c) severe COVID-19 infection treated with dexamethasone from prospective observational cohort studies at Charité-Universit"atsmedizin Berlin, Germany. We analyzed SARS-CoV-2 spike-reactive T cells, spike-specific IgG titers, and serum neutralizing activity against B.1.1.7 and B.1.617.2 in samples ranging from 2 weeks to 6 months after infection. We also analyzed BA.2 neutralization in sera after booster immunization.RESULTSPatients with severe COVID-19 and dexamethasone treatment had lower T cell and antibody responses to SARS-CoV-2 compared with patients without dexamethasone treatment in the early phase of disease, which converged in both groups before 6 months after infection and also after immunization. Patients with mild COVID-19 had comparatively lower T cell and antibody responses than patients with severe disease, including a lower response to booster immunization during convalescence.CONCLUSIONDexamethasone treatment was associated with a short-term reduction in T cell and antibody responses in severe COVID-19 when compared with the nontreated group, but this difference evened out 6 months after infection. We confirm higher cellular and humoral immune responses in patients after severe versus mild COVID-19 and the concept of improved hybrid immunity upon immunization.FUNDINGBerlin Institute of Health, German Federal Ministry of Education, and German Federal Institute for Drugs and Medical Devices.
| DOI: | 10.1172/jci.insight.166711 |
| Pubmed: | 36881474 |
Abstract:
BACKGROUNDAfter its introduction as standard-of-care for severe COVID-19, dexamethasone has been administered to a large number of patients globally. Detailed knowledge of its impact on the cellular and humoral immune response to SARS-CoV-2 remains scarce.METHODSWe included immunocompetent individuals with (a) mild COVID-19, (b) severe COVID-19 before introduction of dexamethasone treatment, and (c) severe COVID-19 infection treated with dexamethasone from prospective observational cohort studies at Charité-Universit"atsmedizin Berlin, Germany. We analyzed SARS-CoV-2 spike-reactive T cells, spike-specific IgG titers, and serum neutralizing activity against B.1.1.7 and B.1.617.2 in samples ranging from 2 weeks to 6 months after infection. We also analyzed BA.2 neutralization in sera after booster immunization.RESULTSPatients with severe COVID-19 and dexamethasone treatment had lower T cell and antibody responses to SARS-CoV-2 compared with patients without dexamethasone treatment in the early phase of disease, which converged in both groups before 6 months after infection and also after immunization. Patients with mild COVID-19 had comparatively lower T cell and antibody responses than patients with severe disease, including a lower response to booster immunization during convalescence.CONCLUSIONDexamethasone treatment was associated with a short-term reduction in T cell and antibody responses in severe COVID-19 when compared with the nontreated group, but this difference evened out 6 months after infection. We confirm higher cellular and humoral immune responses in patients after severe versus mild COVID-19 and the concept of improved hybrid immunity upon immunization.FUNDINGBerlin Institute of Health, German Federal Ministry of Education, and German Federal Institute for Drugs and Medical Devices.
R. Heyder,
N. C. Office,
N. S. Group,
N. Coordination,
R. Coordination,
A. Coordination and
G. S. Group,
"The German Network of University Medicine: technical and organizational approaches for research data platforms",
01
2023.
| DOI: | 10.1007/s00103-022-03649-1 |
[German]
R. Heyder,
N. C. Office,
N. S. Group,
N. Coordination,
R. Coordination,
A. Coordination and
G. S. Group,
"The German Network of University Medicine: technical and organizational approaches for research data platforms",
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz,
vol. 66,
no. 2,
pp. 114—125,
2023.
| DOI: | 10.1007/s00103-022-03649-1 |
[en]
I. Miederer,
J. M. M. Rogasch,
R. Fischer,
T. Fuchs,
C. Lapa,
P. Lohmann,
K. Shi,
J. Tran-Gia,
T. Wendler and
D. Hellwig,
"The Medical Informatics Initiative and the Network University Medicine - Perspectives for Nuclear Medicine",
Nuklearmedizin,
vol. 62,
no. 5,
pp. 276—283,
2023.
Georg Thieme Verlag KG,
http://dx.doi.org/10.1055/a-2067-7642.
Abstract:
Digitization in the healthcare sector and the support of clinical workflows with artificial intelligence (AI), including AI-supported image analysis, represent a great challenge and equally a promising perspective for preclinical and clinical nuclear medicine. In Germany, the Medical Informatics Initiative (MII) and the Network University Medicine (NUM) are of central importance for this transformation. This review article outlines these structures and highlights their future role in enabling privacy-preserving federated multi-center analyses with interoperable data structures harmonized between site-specific IT infrastructures. The newly founded working group "Digitization and AI" in the German Society of Nuclear Medicine (DGN) as well as the Fach- und Organspezifische Arbeitsgruppe (FOSA, specialty- and organ-specific working group) founded for the field of nuclear medicine (FOSA Nuklearmedizin) within the NUM aim to initiate and coordinate measures in the context of digital medicine and (image-)data-driven analyses for the DGN.
| DOI: | 10.1055/a-2067-7642 |
Abstract:
Digitization in the healthcare sector and the support of clinical workflows with artificial intelligence (AI), including AI-supported image analysis, represent a great challenge and equally a promising perspective for preclinical and clinical nuclear medicine. In Germany, the Medical Informatics Initiative (MII) and the Network University Medicine (NUM) are of central importance for this transformation. This review article outlines these structures and highlights their future role in enabling privacy-preserving federated multi-center analyses with interoperable data structures harmonized between site-specific IT infrastructures. The newly founded working group "Digitization and AI" in the German Society of Nuclear Medicine (DGN) as well as the Fach- und Organspezifische Arbeitsgruppe (FOSA, specialty- and organ-specific working group) founded for the field of nuclear medicine (FOSA Nuklearmedizin) within the NUM aim to initiate and coordinate measures in the context of digital medicine and (image-)data-driven analyses for the DGN.
[eng]
J. Lücke,
M. Nawrocki,
J. Schnell,
N. Meins,
F. Heinrich,
T. Zhang,
F. Bertram,
M. Sabihi,
M. Böttcher,
T. Blankenburg,
M. Pfaff,
S. Notz,
J. Kempski,
M. Reeh,
S. Wolter,
O. Mann,
J. R. Izbicki,
M. Lütgehetmann,
A. Duprée,
A. D. Giannou,
B. Ondruschka and
S. Huber,
"TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver",
Frontiers in Immunology,
vol. 14,
pp. 1151937,
2023.
Abstract:
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.
| DOI: | 10.3389/fimmu.2023.1151937 |
Abstract:
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.
[en]
M. S. Woo,
M. Shafiq,
A. Fitzek,
M. Dottermusch,
H. Altmeppen,
B. Mohammadi,
C. Mayer,
L. C. Bal,
L. Raich,
J. Matschke,
S. Krasemann,
S. Pfefferle,
T. T. Brehm,
M. Lütgehetmann,
J. Schädler,
M. M. Addo,
J. Wiesch,
B. Ondruschka,
M. A. Friese and
M. Glatzel,
"Vagus nerve inflammation contributes to dysautonomia in COVID-19",
Acta Neuropathologica,
vol. 146,
no. 3,
pp. 387—394,
Sep.
2023.
Abstract:
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.
| DOI: | 10.1007/s00401-023-02612-x |
| Datei: | https://doi.org/10.1007/s00401-023-02612-x |
Abstract:
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.
S. M. Hopff,
"Vergleich von Akut- und Langzeit-Symptomen bei mit den SARS-CoV-2-Varianten Delta und Omikron infizierten Patient:innen - Ergebnisse des Nationalen Pandemie Kohorten Netzes (NAPKON)",
Vortrag KIT Kongress 2023, Leipzig,
2023.
A. Surov,
M. Thormann,
H. Kardas,
M. Hinnerichs,
J. Omari,
E. Cingöz,
M. Cingöz,
M. Dursun,
İ. Kormaz,
Ç. Orhan,
Ö. Yıldız,
E. Hocaoglu,
E. Inci,
H. Önder,
H. Erk,
O. Chousein,
H. Sasani,
K. Gönen,
M. Pech and
A. Wienke,
"Visceral to subcutaneous fat ratio predicts short-term mortality in patients with Covid 19. A multicenter study",
Br J Radiol,
vol. 96,
no. 1144,
pp. 20220869,
2023.
| DOI: | 10.1259/bjr.20220869 |
R. Mieling,
M. Neidhardt,
S. Latus,
C. Stapper,
S. Gerlach,
I. Kniep,
A. Heinemann,
B. Ondruschka and
A. Schlaefer,
"Collaborative Robotic Biopsy with Trajectory Guidance and Needle Tip Force Feedback"
in 2023 IEEE International Conference on Robotics and Automation (ICRA),
Mai
2023,
pp. 6893—6900.
Abstract:
The diagnostic value of biopsies is highly dependent on the placement of needles. Robotic trajectory guidance has been shown to improve needle positioning, but feedback for real-time navigation is limited. Haptic display of needle tip forces can provide rich feedback for needle navigation by enabling localization of tissue structures along the insertion path. We present a collaborative robotic biopsy system that combines trajectory guidance with kinesthetic feedback to assist the physician in needle placement. The robot aligns the needle while the insertion is performed in collaboration with a medical expert who controls the needle position on site. We present a needle design that senses forces at the needle tip based on optical coherence tomography and machine learning for real-time data processing. Our robotic setup allows operators to sense deep tissue interfaces independent of frictional forces to improve needle placement relative to a desired target structure. We first evaluate needle tip force sensing in ex-vivo tissue in a phantom study. We characterize the tip forces during insertions with constant velocity and demonstrate the ability to detect tissue interfaces in a collaborative user study. Participants are able to detect 91 percent of ex-vivo tissue interfaces based on needle tip force feedback alone. Finally, we demonstrate that even smaller, deep target structures can be accurately sampled by performing post-mortem in situ biopsies of the pancreas.
| DOI: | 10.1109/ICRA48891.2023.10161377 |
Abstract:
The diagnostic value of biopsies is highly dependent on the placement of needles. Robotic trajectory guidance has been shown to improve needle positioning, but feedback for real-time navigation is limited. Haptic display of needle tip forces can provide rich feedback for needle navigation by enabling localization of tissue structures along the insertion path. We present a collaborative robotic biopsy system that combines trajectory guidance with kinesthetic feedback to assist the physician in needle placement. The robot aligns the needle while the insertion is performed in collaboration with a medical expert who controls the needle position on site. We present a needle design that senses forces at the needle tip based on optical coherence tomography and machine learning for real-time data processing. Our robotic setup allows operators to sense deep tissue interfaces independent of frictional forces to improve needle placement relative to a desired target structure. We first evaluate needle tip force sensing in ex-vivo tissue in a phantom study. We characterize the tip forces during insertions with constant velocity and demonstrate the ability to detect tissue interfaces in a collaborative user study. Participants are able to detect 91 percent of ex-vivo tissue interfaces based on needle tip force feedback alone. Finally, we demonstrate that even smaller, deep target structures can be accurately sampled by performing post-mortem in situ biopsies of the pancreas.
L. Gallée,
M. Beer and
M. Götz,
"Interpretable Medical Image Classification Using Prototype Learning and Privileged Information"
in Medical Image Computing and Computer Assisted Intervention — MICCAI 2023,
Greenspan, Hayit
and Madabhushi, Anant
and Mousavi, Parvin
and Salcudean, Septimiu
and Duncan, James
and Syeda-Mahmood, Tanveer
and Taylor, Russell, Eds.
Cham:
Springer Nature Switzerland,
2023,
pp. 435—445.
Abstract:
Interpretability is often an essential requirement in medical imaging. Advanced deep learning methods are required to address this need for explainability and high performance. In this work, we investigate whether additional information available during the training process can be used to create an understandable and powerful model. We propose an innovative solution called Proto-Caps that leverages the benefits of capsule networks, prototype learning and the use of privileged information. Evaluating the proposed solution on the LIDC-IDRI dataset shows that it combines increased interpretability with above state-of-the-art prediction performance. Compared to the explainable baseline model, our method achieves more than 6 $$\backslash%$$%higher accuracy in predicting both malignancy (93.0 $$\backslash%$$%) and mean characteristic features of lung nodules. Simultaneously, the model provides case-based reasoning with prototype representations that allow visual validation of radiologist-defined attributes.
| DOI: | https://doi.org/10.1007/978-3-031-43895-0_41 |
| ISBN: | 978-3-031-43895-0 |
Abstract:
Interpretability is often an essential requirement in medical imaging. Advanced deep learning methods are required to address this need for explainability and high performance. In this work, we investigate whether additional information available during the training process can be used to create an understandable and powerful model. We propose an innovative solution called Proto-Caps that leverages the benefits of capsule networks, prototype learning and the use of privileged information. Evaluating the proposed solution on the LIDC-IDRI dataset shows that it combines increased interpretability with above state-of-the-art prediction performance. Compared to the explainable baseline model, our method achieves more than 6 $$\backslash%$$%higher accuracy in predicting both malignancy (93.0 $$\backslash%$$%) and mean characteristic features of lung nodules. Simultaneously, the model provides case-based reasoning with prototype representations that allow visual validation of radiologist-defined attributes.
T. J. Hartung,
C. Neumann,
T. Bahmer,
I. Chaplinskaya-Sobol,
M. Endres,
J. Geritz,
K. G. Haeusler,
P. Heuschmann,
H. Hildesheim,
A. Hinz,
S. Hopff,
A. Horn,
M. Krawczak,
L. Krist,
J. Kudelka,
W. Lieb,
C. Maetzler,
A. Mehnert-Theuerkauf,
F. Montellano,
C. Morbach,
S. Schmidt,
S. Schreiber,
F. Steigerwald,
S. Störk,
W. Maetzler and
C. Finke,
"Fatigue and cognitive impairment after COVID-19: A prospective multicentre study.",
EClinicalMedicine,
09
2022.
| DOI: | 10.1016/j.eclinm.2022.101651 |
N. Hettich,
"Lebensqualität von COVID-19 Erkrankten im Verlauf (Analyse aus dem NAPKON Projekt)",
Vortrag Deutscher Kongress für Physikalische und Rehabilitative Medizin,
09
2022.
M. Weigl and
C. Lemhöfer,
"Leistungen zur Frührehabilitation während und nach dem akutstationären NAPKON Erweiterungsmodul zur Analyse von Pat. in Rehabilitationskliniken nach COVID-19",
Vortrag Deutscher Kongress für Physikalische und Rehabilitative Medizin,
09
2022.
S. Hopff,
"Netzwerk Universitätsmedizin - Aufbau und Projekte inkl. NAPKON",
ortrag Deutscher Kongress für Physikalische und Rehabilitative Medizin,
09
2022.
M. Weigl,
"Post-COVID: Prognostische Faktoren für Einschränkungen der Arbeitsfähigkeit und Bedarf an Rehabilitation (Analyse aus dem NAPKON Projekt",
Vortrag Deutscher Kongress für Physikalische und Rehabilitative Medizin,
09
2022.
K. O. Yusuf,
O. Miljukov,
A. Schoneberg and
S. Hanß,
"Consistency as a Data Quality Measure for German Corona Consensus items mapped from National Pandemic Cohort Network data collections.",
Methods Inf Med,
07
2022.
| DOI: | 10.1055/a-2006-1086 |
T. Bahmer,
"Severity Score-Based Study of Predictors and Clinical Correlates of Post-COVID Syndrome (PCS) in the German Population",
07
2022.
| DOI: | 10.1016/j.eclinm.2022.101549 |
M. Schons,
L. Pilgram and
J. Reese,
"The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.",
European Journal of Epidemiology 37(8),
07
2022.
| DOI: | 10.1007/s10654-022-00896-z |
L. Fiedler-Lacombe,
E. Heim,
H. Valentin,
H. Rau,
A. Blumentritt,
D. Stahl,
M. Kraus and
B. Lorenz-Depiereux,
"Herausforderungen des Einwilligungsmanagements von Minderjährigen bei Kohortenstudien",
16. DVMD-Fachtagung,
05
2022.
H. Rau,
A. Blumentritt,
D. Stahl and
u. T. d. U. G. K. d. ö. R.,
"Qualitätsgesichertes Management von Einwilligungserklärungen – Ein Appell zur Nutzung elektronischer Einwilligungserhebungen für zeitkritische klinische Forschung. 16. DVMD-Fachtagung, 12.05.2022",
05
2022.
H. Rau,
A. Blumentritt and
D. Stahl,
"Unabhängige Treuhandstelle der Universitätsmedizin Greifswald K.d.ö.R. Qualitätsgesichertes Management von Einwilligungserklärungen – Ein Appell zur Nutzung elektronischer Einwilligungserhebungen für zeitkritische klinische Forschung",
16. DVMD-Fachtagung,
05
2022.
E. Heim,
H. Valentin,
H. Rau,
A. Blumentritt,
D. Stahl,
M. Stecher,
M. Kraus and
B. Lorenz-Depiereux,
"Widerrufs- und Ausschlussmanagement unter Berücksichtigung komplexer Konstellationen in der COVID-19-Forschung am Beispiel NUM",
16. DVMD-Fachtagung,
05
2022.
S. Hopff,
K. Tilch,
M. Kraus,
B. Lorenz-Depiereux,
G. Anton,
K. Appel,
T. Bahmer,
A. Bartschke,
C. Bellinghausen,
I. Bernemann,
M. Brechtel,
C. Brünn,
C. Fiessler,
R. Geisler,
S. Hansch,
F. Hanses,
S. Hanß,
R. Heyder,
A. Hoffmann,
A. Horn,
C. Jakob,
S. Jiru-Hillmann,
T. Keil,
Y. Khodamoradi,
M. Kohls,
D. Krefting,
S. Kunze,
F. Kurth,
W. Lieb,
L. J. Lippert,
R. Lorbeer,
L. Lysyakova,
C. Maetzler,
O. Miljukov,
M. Nauck,
L. Pilgram,
V. Püntmann,
J. Reese,
L. Reinke,
S. Rudolph,
J. Sass,
C. Schäfer,
J. Schaller,
M. Schattschneider,
C. Scheer,
M. Scherer,
J. Schmidt,
S. Schmidt,
M. Schons,
K. Seibel,
D. Stahl,
M. Stecher,
F. Steinbeis,
S. Störk,
M. Tauchert,
C. Thibeault,
N. Töpfner,
K. Ungethüm,
H. Valentin,
S. Wiedmann,
T. Zoller,
R. Berner,
M. Krawczak,
E. Nagel,
T. Illig,
S. Schreiber,
M. Witzenrath,
P. Heuschmann and
J. J. Vehreschild,
"Ethical and coordinative challenges in setting up a national cohort study exemplified by the German National Pandemic Cohort Network (NAPKON)",
Oral presentation Kongress ECCMID 04/2022,
04
2022.
D. Stahl,
"Vollelektronische Erfassung von Einwilligungen (Informed Consents) mittels Tablets. Lohfert – Preis.",
no. https://www.christophlohfert-stiftung.de/panorama/ausschreibung-fuer-den-lohfert-preis-2022-beendet/,
02
2022.
L. Triefenbach,
R. Otto,
J. Bienzeisler,
A. Kombeiz,
S. Ehrentreich,
R. Röhrig,
R. W. Majeed and
Aktin Research Group,
"Establishing a data quality baseline in the AKTIN Emergency Department Data Registry – A secondary use perspective",
Stud Health Technol Inform.,
vol. 294,
no. 25,
pp. 209-213,
Mai
2022.
| DOI: | https://doi.org/10.3233/shti220439 |
| Pubmed: | 35612058 |
C. Werlein,
M. Ackermann,
H. Stark,
A. Tzankov,
J. D. Haslbauer and
et al,
"Inflammation and vascular remodeling in COVID-19 hearts",
Angiogenesis,
vol. 26,
pp. 233-248,
Nov.
2022.
| DOI: | https://doi.org/10.1007/s10456-022-09860-7 |
T. Aschman,
R. Mothes,
F. Heppner and
H. Radbruch,
"What SARS-CoV-2 does to our brains",
Immunity,
vol. 55,
no. 7,
pp. 1159-1172,
Jul.
2022.
| DOI: | https://doi.org/10.1016/j.immuni.2022.06.013 |
P. Georg,
R. Astaburuaga-García,
L. Bonaguro,
S. Brumhard,
L. Michalick,
L. Lippert and
et al,
"Complement activation induces excessive T cell cytotoxicity in severe COVID-19",
Cell,
vol. 185,
no. 3,
pp. 493-512,
Feb.
2022.
| DOI: | https://doi.org/10.1016/j.cell.2021.12.040 |
R. Ameratunga,
S. Woon,
M. Sheppard,
J. Garland,
B. Ondruschka,
C. X. Wong and
et al,
"First Identified Case of Fatal Fulminant Necrotizing Eosinophilic Myocarditis Following the Initial Dose of the Pfizer-BioNTech mRNA COVID-19 Vaccine (BNT162b2, Comirnaty): an Extremely Rare Idiosyncratic Hypersensitivity Reaction",
Journal of Clinical Immunology,
vol. 42,
pp. 441-447,
Jan.
2022.
| DOI: | https://doi.org/10.1007/s10875-021-01187-0 |
Z. Wang,
A. Cryar,
O. Lemke,
P. Tober-Lau,
D. Ludwig,
E. Helbig,
S. Hippenstiel,
L. Sander,
D. Blake,
C. Lane and
others,
"A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study",
EClinicalMedicine,
vol. 49,
pp. 101495,
2022.
| DOI: | 10.1016/j.eclinm.2022.101495 |
V. Demichev and
et al,
"A proteomic survival predictor for COVID-19 patients in intensive care",
PLOS Digital Health,
vol. 1,
pp. e0000007,
2022.
| DOI: | 10.1371/journal.pdig.0000007 |
S. Würstle,
J. Erber,
M. Hanselmann and
others,
"A telemedicine-guided self-collection approach for PCR-based SARS-CoV-2 testing: Comparative study",
JMIR Formative Research,
vol. 6,
no. 1,
2022.
| DOI: | 10.2196/32564 |
| Datei: | https://doi.org/10.2196/32564 |
F. Meng,
J. Kottlors,
R. Shahzad,
H. Liu,
P. Fervers,
Y. Jin,
M. Rinneburger,
D. Le,
M. Weisthoff,
W. Liu,
M. Ni,
Y. Sun,
L. An,
X. Huai,
D. Móré,
A. Giannakis,
I. Kaltenborn,
A. Bucher,
D. Maintz,
L. Zhang,
F. Thiele,
M. Li,
M. Perkuhn,
H. Zhang and
T. Persigehl,
"AI support for accurate and fast radiological diagnosis of COVID-19: an international multicenter, multivendor CT study",
Eur Radiol,
2022.
| DOI: | 10.1007/s00330-022-09335-9 |
M. Wygrecka,
A. Birnhuber,
B. Seeliger,
L. Michalick,
O. Pak,
A. Schultz,
F. Schramm,
M. Zacharias,
G. Gorkiewicz,
S. David,
T. Welte,
J. Schmidt,
N. Weissmann,
R. Schermuly,
G. Barreto,
L. Schaefer,
P. Markart,
M. Brack,
S. Hippenstiel,
F. Kurth,
L. Sander,
M. Witzenrath,
W. Kuebler,
G. Kwapiszewska and
K. Preissner,
"Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19",
Blood Adv,
vol. 6,
no. 3,
pp. 1074—1087,
2022.
| DOI: | 10.1182/bloodadvances.2021004816 |
D. Gagiannis,
V. G. Umathum,
W. Bloch,
C. Rother,
M. Stahl,
H. M. Witte,
S. Djudjaj,
P. Boor and
K. Steinestel,
"Antemortem vs Postmortem Histopathologic and Ultrastructural Findings in Paired Transbronchial Biopsy Specimens and Lung Autopsy Samples From Three Patients With Confirmed SARS-CoV-2",
American Journal of Clinical Pathology,
vol. 157,
no. 1,
pp. 54—63,
Jan.
2022.
Abstract:
Respiratory failure is the major cause of death in coronavirus disease 2019 (COVID-19). Autopsy-based reports describe diffuse alveolar damage (DAD), organizing pneumonia, and fibrotic change, but data on early pathologic changes and during progression of the disease are rare.We prospectively enrolled three patients with COVID-19 and performed full clinical evaluation, including high-resolution computed tomography. We took transbronchial biopsy (TBB) specimens at different time points and autopsy tissue samples for histopathologic and ultrastructural evaluation after the patients’ death.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction and/or fluorescence in situ hybridization in all TBBs. Lung histology showed reactive pneumocytes and capillary congestion in one patient who died shortly after hospital admission with detectable virus in one of two lung autopsy samples. SARS-CoV-2 was detected in two of two autopsy samples from another patient with a fulminant course and very short latency between biopsy and autopsy, showing widespread organizing DAD. In a third patient with a prolonged course, autopsy samples showed extensive fibrosis without detectable virus.We report the course of COVID-19 in paired biopsy specimens and autopsies, illustrating vascular, organizing, and fibrotic patterns of COVID-19–induced lung injury. Our results suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.
| DOI: | 10.1093/ajcp/aqab087 |
| Datei: | https://doi.org/10.1093/ajcp/aqab087 |
Abstract:
Respiratory failure is the major cause of death in coronavirus disease 2019 (COVID-19). Autopsy-based reports describe diffuse alveolar damage (DAD), organizing pneumonia, and fibrotic change, but data on early pathologic changes and during progression of the disease are rare.We prospectively enrolled three patients with COVID-19 and performed full clinical evaluation, including high-resolution computed tomography. We took transbronchial biopsy (TBB) specimens at different time points and autopsy tissue samples for histopathologic and ultrastructural evaluation after the patients’ death.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction and/or fluorescence in situ hybridization in all TBBs. Lung histology showed reactive pneumocytes and capillary congestion in one patient who died shortly after hospital admission with detectable virus in one of two lung autopsy samples. SARS-CoV-2 was detected in two of two autopsy samples from another patient with a fulminant course and very short latency between biopsy and autopsy, showing widespread organizing DAD. In a third patient with a prolonged course, autopsy samples showed extensive fibrosis without detectable virus.We report the course of COVID-19 in paired biopsy specimens and autopsies, illustrating vascular, organizing, and fibrotic patterns of COVID-19–induced lung injury. Our results suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.
[eng]
S. Krasemann,
C. Dittmayer,
S. Stillfried,
J. Meinhardt,
F. Heinrich,
K. Hartmann,
S. Pfefferle,
E. Thies,
R. Manitius,
T. A. D. Aschman,
J. Radke,
A. Osterloh,
S. Schmid,
E. M. Buhl,
J. Ihlow,
F. Dubois,
V. Arnhold,
S. Elezkurtaj,
D. Horst,
A. Hocke,
S. Timm,
S. Bachmann,
V. Corman,
H. Goebel,
J. Matschke,
S. Stanelle-Bertram,
G. Gabriel,
D. Seilhean,
H. Adle-Biassette,
B. Ondruschka,
M. Ochs,
W. Stenzel,
F. L. Heppner,
P. Boor,
H. Radbruch,
M. Laue and
M. Glatzel,
"Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses",
EBioMedicine,
vol. 83,
pp. 104193,
Sep.
2022.
Abstract:
BACKGROUND: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing. METHODS: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2. FINDINGS: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value \textless0.0001). For EM, we refined criteria for virus identification and provide recommendations for optimized sampling and analysis. 135 of 144 publications misinterpret cellular structures as virus using EM or show only insufficient data. We provide publicly accessible digitized EM sections as a reference and for training purposes. INTERPRETATION: Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2. FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, Berlin University Alliance, German Research Foundation, German Center for Infectious Research.
| DOI: | 10.1016/j.ebiom.2022.104193 |
Abstract:
BACKGROUND: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing. METHODS: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2. FINDINGS: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value \textless0.0001). For EM, we refined criteria for virus identification and provide recommendations for optimized sampling and analysis. 135 of 144 publications misinterpret cellular structures as virus using EM or show only insufficient data. We provide publicly accessible digitized EM sections as a reference and for training purposes. INTERPRETATION: Since detection of SARS-CoV-2 in human autopsy tissues by IHC and EM is difficult and frequently incorrect, we propose criteria for a re-evaluation of available data and guidance for further investigations of direct organ effects by SARS-CoV-2. FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, Berlin University Alliance, German Research Foundation, German Center for Infectious Research.
L. Buhr,
S. Schicktanz and
E. Nordmeyer,
"Attitudes Toward Mobile Apps for Pandemic Research Among Smartphone Users in Germany: National Survey",
JMIR Mhealth Uhealth,
vol. 10,
no. 1,
pp. e31857,
2022.
| DOI: | 10.2196/31857 |
S. R. Schulz and
et al,
"Augmented Neutralization of SARS-CoV-2 Omicron Variant by Boost Vaccination and Monoclonal Antibodies",
European journal of immunology,
2022.
| DOI: | 10.1002/eji.202249841 |
B. Schmid,
M. Griesel,
A. Fischer,
C. S. Romero,
M. Metzendorf,
S. Weibel and
F. Fichtner,
"Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis",
J Clin Med,
vol. 11,
no. 2,
pp. 391,
2022.
| DOI: | 10.3390/jcm11020391 |
A. F. Demleitner,
A. Wolff,
J. Erber and
et al,
"Best practice approaches to outpatient management of people living with Parkinson's disease during the COVID-19 pandemic",
J Neural Transm (Vienna),
vol. 129,
no. 11,
pp. 1377-1385,
2022.
| DOI: | https://doi.org/10.1007/s00702-022-02484-7 |
T. Lingscheid,
L. Lippert,
D. Hillus,
T. Kruis,
C. Thibeault,
E. Helbig,
P. Tober-Lau,
F. Pfäfflin,
H. Müller-Redetzky,
M. Witzenrath,
T. Zoller,
A. Uhrig,
B. Opitz,
N. Suttorp,
T. Kramer,
L. Sander,
M. Stegemann and
F. Kurth,
"Characterization of antimicrobial use and co-infections among hospitalized patients with COVID-19: a prospective observational cohort study",
Infection,
vol. 50,
no. 6,
pp. 1441—1452,
2022.
| DOI: | 10.1007/s15010-022-01796-w |
A. Walker,
T. Houwaart,
P. Finzer,
L. Ehlkes,
A. Tyshaieva,
M. Damagnez,
D. Strelow,
A. Duplessis,
J. Nicolai,
T. Wienemann,
T. Tamayo,
M. Kohns Vasconcelos,
L. Hülse,
K. Hoffmann,
N. Lübke,
S. Hauka,
M. Andree,
M. P. Däumer,
A. Thielen,
S. Kolbe-Busch,
K. Göbels,
R. Zotz,
K. Pfeffer,
J. Timm and
A. T. Dilthey,
"Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Clusters Based on Integrated Genomic Surveillance, Outbreak Analysis and Contact Tracing in an Urban Setting",
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,
vol. 74,
no. 6,
pp. 1039—1046,
2022.
Abstract:
BACKGROUND Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. METHODS In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. RESULTS Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. CONCLUSIONS Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.
| DOI: | 10.1093/cid/ciab588 |
Abstract:
BACKGROUND Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. METHODS In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. RESULTS Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. CONCLUSIONS Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.
M. Schmidt,
S. Gebauer,
A. Bartholmes,
D. Kadioglu,
J. Kleesiek,
B. Hamm,
T. Vogl,
T. Penzkofer,
A. Bucher and
H. Storf,
"CODEX Meets RACOON - A Concept for Collaborative Documentation of Clinical and Radiological COVID-19 Data",
Stud Health Technol Inform,
2022.
| DOI: | 10.3233/SHTI220804 |
A. Dulovic and
et al,
"Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany",
Frontiers in Immunology,
vol. 13,
pp. 828053,
2022.
| DOI: | 10.3389/fimmu.2022.828053 |
P. Georg,
R. Astaburuaga-García,
L. Bonaguro,
S. Brumhard,
L. Michalick and
e. a. Lippert,
"Complement activation induces excessive T cell cytotoxicity in severe COVID-19",
Cell,
vol. 185,
pp. 493—512.e425,
2022.
J. Brandner,
P. Boor,
L. Borcherding and
et al,
"Contamination of personal protective equipment during COVID-19 autopsies",
Virchows Arch,
pp. 1-10,
2022.
| DOI: | 10.1007/s00428-021-03263-7 |
E. Schäfer,
C. Scheer,
K. Saljé,
A. Fritz,
T. Kohlmann,
N. Hübner,
M. Napp,
L. Fiedler-Lacombe,
D. Stahl,
B. Rauch,
M. Nauck,
U. Völker,
S. Felix,
G. Lucchese,
A. Flöel,
S. Engeli,
W. Hoffmann,
K. Hahnenkamp and
M. Tzvetkov,
"Course of disease and risk factors for hospitalization in outpatients with a SARS‑CoV‑2 infection.",
SCIENTIFIC REPORTS. (open access) 2022; 12(1):7249,
2022.
C. Scheer,
L. Fiedler-Lacombe,
D. Stahl,
M. Nauck,
W. Hoffmann,
E. Schäfer,
K. Saljé,
A. Fritz,
T. Kohlmann,
N. Hübner,
M. Napp,
B. Rauch,
U. Völker,
S. Felix,
G. Lucchese,
A. Flöel,
S. Engeli,
K. Hahnenkamp and
M. Tzvetkov,
"Course of disease and risk factors for hospitalization in outpatients with a SARS‑CoV‑2 infection.",
SCIENTIFIC REPORTS. (open access) 2022; 12(1):7249,
2022.