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  1. Article ; Online: Contamination of personal protective equipment during COVID-19 autopsies.

    Brandner, Johanna M / Boor, Peter / Borcherding, Lukas / Edler, Carolin / Gerber, Sven / Heinemann, Axel / Hilsenbeck, Julia / Kasajima, Atsuko / Lohner, Larissa / Märkl, Bruno / Pablik, Jessica / Schröder, Ann Sophie / Slotta-Huspenina, Julia / Sommer, Linna / Sperhake, Jan-Peter / von Stillfried, Saskia / Dintner, Sebastian

    Virchows Archiv : an international journal of pathology

    2022  Volume 480, Issue 3, Page(s) 519–528

    Abstract: Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized ...

    Abstract Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized as indispensable tools for understanding COVID-19, but the true risk of infection to autopsy staff is nevertheless still debated. To clarify the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine points in the PPE of one physician and one assistant after each of 11 full autopsies performed at four centers. Swabs were also obtained from three minimally invasive autopsies (MIAs) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls, and SARS-CoV-2 RNA was detected by real-time RT-PCR. In 9 of 11 full autopsies, PPE samples tested RNA positive through PCR, accounting for 41 of the 198 PPE samples taken (21%). The main contaminated items of the PPE were gloves (64% positive), aprons (50% positive), and the tops of shoes (36% positive) while the fronts of safety goggles, for example, were positive in only 4.5% of the samples, and all the face masks were negative. In MIAs, viral RNA was observed in one sample from a glove but not in other swabs. Infectious virus isolation in cell culture was performed on RNA-positive swabs from the full autopsies. Of all the RNA-positive PPE samples, 21% of the glove samples, taken in 3 of 11 full autopsies, tested positive for infectious virus. In conclusion, PPE was contaminated with viral RNA in 82% of autopsies. In 27% of autopsies, PPE was found to be contaminated even with infectious virus, representing a potential risk of infection to autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore essential to ensure a safe work environment.
    MeSH term(s) Autopsy ; COVID-19/prevention & control ; Humans ; Pandemics/prevention & control ; Personal Protective Equipment ; RNA, Viral/genetics ; SARS-CoV-2
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2022-01-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-021-03263-7
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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Pathologic responses in oligometastatic NSCLC patients treated with neoadjuvant immune checkpoint blockade with and without chemotherapy followed by surgery.

    Boch, Tobias / Frost, Nikolaj / Sommer, Linna / Overbeck, Tobias R / Michaeli, Christoph T / Szuszies, Chrisoph J / Rieckmann, Lisa-Marie / Beumer, Niklas / Imbusch, Charles D / Winter, Hauke / Thomas, Michael / Roeper, Julia / Janning, Melanie / Griesinger, Frank / Wermke, Martin / Loges, Sonja

    Lung cancer (Amsterdam, Netherlands)

    2021  Volume 164, Page(s) 46–51

    Abstract: Objectives: Immune checkpoint inhibitors (ICI) have significantly improved outcome of patients with advanced NSCLC and recently also showed benefit in early-stage disease. Patients with oligometastatic disease (OMD) harbor limited metastases, resectable ...

    Abstract Objectives: Immune checkpoint inhibitors (ICI) have significantly improved outcome of patients with advanced NSCLC and recently also showed benefit in early-stage disease. Patients with oligometastatic disease (OMD) harbor limited metastases, resectable primary tumors and derive benefit from treatment with multimodal locally ablative and systemic therapy approaches. Nothing is known about feasibility and efficacy of neoadjuvant ICI in this setting.
    Material and methods: We here provide data from a multicenter retrospective study comprising 13 patients with NSCLC and OMD (≤3 distant metastases) from 5 university medical centers in Germany who have been treated with neoadjuvant ICI alone (n = 4) or in combination with chemotherapy (CT) (n = 9) prior to resection of the primary tumor. We analyzed complete (pCR) and major pathological remission (MPR) rates.
    Results: These data show that neoadjuvant immunotherapy applied mostly in combination with CT results in high rates of pCR and MPR (54 and 69%, respectively). Up to now, 85% of patients are free of progression with a median follow-up of 9 months (3-28 months). Single cell RNASeq analysis of tumor tissue from one patient treated with CT-ICI indicates a strong predominance of adaptive immune cell populations over a small minority of epithelial (tumor) cells.
    Conclusion: Neoadjuvant ICI with or without CT is a promising therapeutic concept in patients with OMD.
    MeSH term(s) Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/drug therapy ; Neoadjuvant Therapy ; Retrospective Studies
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2021-11-23
    Publishing country Ireland
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2021.11.009
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    Zs.A 2135: Show issues Location:
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  3. Article ; Online: Outcome of First-Line Treatment With Pembrolizumab According to KRAS/TP53 Mutational Status for Nonsquamous Programmed Death-Ligand 1-High (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer.

    Bischoff, Philip / Reck, Martin / Overbeck, Tobias / Christopoulos, Petros / Rittmeyer, Achim / Lüders, Heike / Kollmeier, Jens / Kulhavy, Jonas / Kemper, Marcel / Reinmuth, Niels / Röper, Julia / Janning, Melanie / Sommer, Linna / Aguinarte, Lukas / Koch, Myriam / Wiesweg, Marcel / Wesseler, Claas / Waller, Cornelius F / Kauffmann-Guerrero, Diego /
    Stenzinger, Albrecht / Stephan-Falkenau, Susann / Trautmann, Marcel / Lassmann, Silke / Tiemann, Markus / Klauschen, Frederick / Sebastian, Martin / Griesinger, Frank / Wolf, Jürgen / Loges, Sonja / Frost, Nikolaj

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2023  Volume 19, Issue 5, Page(s) 803–817

    Abstract: Introduction: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. ... ...

    Abstract Introduction: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap.
    Methods: A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of The Cancer Genome Atlas lung adenocarcinoma cohort.
    Results: Proportion of KRASmut and TP53mut was 53% (G12C 25%, non-G12C 28%) and 51%, respectively. In KRASmut patients, TP53 comutations increased response rates (G12C: 69.7% versus 46.5% [TP53mut versus wild-type (wt)], p = 0.004; non-G12C: 55.4% versus 39.5%, p = 0.03), progression-free survival (G12C: hazard ratio [HR] = 0.59, p = 0.009, non-G12C: HR = 0.7, p = 0.047), and overall survival (G12C: HR = 0.72, p = 0.16, non-G12C: HR = 0.56, p = 0.002), whereas no differences were observed in KRASwt patients. After a median follow-up of 41 months, G12C/TP53mut patients experienced the longest progression-free survival and overall survival (33.7 and 65.3 mo), which correlated with high tumor-infiltrating lymphocyte densities in the TME and up-regulation of interferon gamma target genes. Proinflammatory pathways according to TP53 status (mut versus wt) were less enhanced and not different in non-G12C and KRASwt, respectively.
    Conclusions: G12C/TP53 comutations identify a subset of patients with a very favorable long-term survival with immune checkpoint inhibitor monotherapy, mediated by highly active interferon gamma signaling in a proinflammatory TME.
    MeSH term(s) Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Male ; Female ; Antibodies, Monoclonal, Humanized/therapeutic use ; Tumor Suppressor Protein p53/genetics ; Aged ; Mutation ; Retrospective Studies ; Middle Aged ; Germany ; Antineoplastic Agents, Immunological/therapeutic use ; Aged, 80 and over ; B7-H1 Antigen/metabolism ; B7-H1 Antigen/genetics ; Adult ; Treatment Outcome
    Chemical Substances pembrolizumab (DPT0O3T46P) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Antibodies, Monoclonal, Humanized ; Tumor Suppressor Protein p53 ; KRAS protein, human ; TP53 protein, human ; Antineoplastic Agents, Immunological ; CD274 protein, human ; B7-H1 Antigen
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2023.12.015
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    Zs.A 6664: Show issues Location:
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  4. Article ; Online: Contamination of personal protective equipment during COVID-19 autopsies

    Brandner, Johanna M / Boor, Peter / Borcherding, Lukas S / Edler, Carolin / Gerber, Sven / Heinemann, Axel / Hilsenbeck, Julia / Kasajima, Atsuko / Lohner, Larissa / Märkl, Bruno / Pablik, Jessica / Schröder, Ann Sophie / Sommer, Linna / Slotta-Huspenina, Julia / Sperhake, Jan-Peter / von Stillfried, Saskia / Dintner, Sebastian

    medRxiv

    Abstract: Confronted with an emerging infectious disease, the medical community faced relevant concerns regarding the performance of autopsies of COVID-19 deceased at the beginning of the pandemic. This attitude has changed, and autopsies are now recognized as ... ...

    Abstract Confronted with an emerging infectious disease, the medical community faced relevant concerns regarding the performance of autopsies of COVID-19 deceased at the beginning of the pandemic. This attitude has changed, and autopsies are now recognized as indispensable tools for elucidating COVID-19; despite this, the true risk of infection for autopsy staff is still debated. To elucidate the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine locations of the PPE of one physician and an assistant each from 11 full autopsies performed at four different centers. Further samples were obtained for three minimally invasive autopsies (MIA) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls. SARS-CoV-2 RNA was detected by RT-qPCR. In 9/11 full autopsies PPE samples were tested RNA positive with PCR, in total 21% of all PPE samples taken. The main contaminated parts of the PPE were the gloves (64% positive), the aprons (50% positive), and the upper sides of shoes (36% positive) while for example the fronts of safety goggles were only positive in 4.5% of the samples and all face masks were negative. In MIA, viral RNA was observed in one sample from a glove, but not in other swabs. Infectious virus isolation in cell culture was performed in RNA positive swabs from full autopsies. Of all RNA positive PPE samples, 21% of the glove samples were positive for infectious virus taken in 3/11 full autopsies. In conclusion, in >80% of autopsies, PPE was contaminated with viral RNA. In >25% of autopsies, PPE was found to be even contaminated with infectious virus, signifying a potential risk of infection among autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore mandatory to enable safe work environment.
    Keywords covid19
    Language English
    Publishing date 2021-07-15
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.07.12.21260357
    Database COVID19

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  5. Article ; Online: Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?

    Jonigk, Danny / Werlein, Christopher / Acker, Till / Aepfelbacher, Martin / Amann, Kerstin U / Baretton, Gustavo / Barth, Peter / Bohle, Rainer M / Büttner, Andreas / Büttner, Reinhard / Dettmeyer, Reinhard / Eichhorn, Philip / Elezkurtaj, Sefer / Esposito, Irene / Evert, Katja / Evert, Matthias / Fend, Falko / Gaßler, Nikolaus / Gattenlöhner, Stefan /
    Glatzel, Markus / Göbel, Heike / Gradhand, Elise / Hansen, Torsten / Hartmann, Arndt / Heinemann, Axel / Heppner, Frank L / Hilsenbeck, Julia / Horst, David / Kamp, Jan C / Mall, Gita / Märkl, Bruno / Ondruschka, Benjamin / Pablik, Jessica / Pfefferle, Susanne / Quaas, Alexander / Radbruch, Helena / Röcken, Christoph / Rosenwald, Andreas / Roth, Wilfried / Rudelius, Martina / Schirmacher, Peter / Slotta-Huspenina, Julia / Smith, Kevin / Sommer, Linna / Stock, Konrad / Ströbel, Philipp / Strobl, Stephanie / Titze, Ulf / Weirich, Gregor / Weis, Joachim / Werner, Martin / Wickenhauser, Claudia / Wiech, Thorsten / Wild, Peter / Welte, Tobias / von Stillfried, Saskia / Boor, Peter

    Virchows Archiv : an international journal of pathology

    2022  Volume 481, Issue 2, Page(s) 139–159

    Abstract: The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern ... ...

    Abstract The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.
    MeSH term(s) Autopsy ; COVID-19 ; Humans ; Lung/pathology ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2022-04-01
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-022-03319-2
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