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1. Purification of a single-photon nonlinearity

Author: H. Snijders, J. A. Frey, J. Norman, M. P. Bakker, E. C. Langman, A. Gossard, J. E. Bowers, M. P. van Exter, D. Bouwmeester, and W. Löffler
Subjects: Science
Abstract: Single-photon optical nonlinearity is possible using an optical cavity to create strong coupling between a cavity mode and a two-level quantum system. Here, the authors demonstrate it is also possible in the weak-coupling regime by using quantum interference in a polarization-degenerate cavity.
Published: 2016
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2. A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2

Author: Alena Reguzova, Melanie Müller, Felix Pagallies, Dominique Burri, Ferdinand Salomon, Hanns-Joachim Rziha, Zsofia Bittner-Schrader, Babs E. Verstrepen, Kinga P. Böszörményi, Ernst J. Verschoor, Ingo Gerhauser, Knut Elbers, Meral Esen, Alessandro Manenti, Martina Monti, Hans-Georg Rammensee, Madiha Derouazi, Markus W. Löffler, and Ralf Amann
Subjects: Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine.
Published: 2024
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3. Identification and relative abundance of naturally presented and cross-reactive influenza A virus MHC class I-restricted T cell epitopes

Author: Hazem Hamza, Michael Ghosh, Markus W. Löffler, Hans-Georg Rammensee, and Oliver Planz
Subjects: Influenza virus, CD8 T cells, HLA class I, T-cell epitope, immunopeptidomics, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract: Cytotoxic T lymphocytes are key for controlling viral infection. Unravelling CD8+ T cell-mediated immunity to distinct influenza virus strains and subtypes across prominent HLA types is relevant for combating seasonal infections and emerging new variants. Using an immunopeptidomics approach, naturally presented influenza A virus-derived ligands restricted to HLA-A*24:02, HLA-A*68:01, HLA-B*07:02, and HLA-B*51:01 molecules were identified. Functional characterization revealed multifunctional memory CD8+ T cell responses for nine out of sixteen peptides. Peptide presentation kinetics was optimal around 12 h post infection and presentation of immunodominant epitopes shortly after infection was not always persistent. Assessment of immunogenic epitopes revealed that they are highly conserved across the major zoonotic reservoirs and may contain a single substitution in the vicinity of the anchor residues. These findings demonstrate how the identified epitopes promote T cell pools, possibly cross-protective in individuals and can be potential targets for vaccination.
Published: 2024
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4. Peptide-stimulated T cells bypass immune checkpoint inhibitor resistance and eliminate autologous microsatellite instable colorectal cancer cells

Author: Sandra Schwarz, Zhaoran Su, Mathias Krohn, Markus W. Löffler, Andreas Schlosser, and Michael Linnebacher
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Two hypermutated colon cancer cases with patient-derived cell lines, peripheral and tumor-infiltrating T cells available were selected for detailed investigation of immunological response. T cells co-cultured with autologous tumor cells showed only low levels of pro-inflammatory cytokines and failed at tumor recognition. Similarly, treatment of co-cultures with immune checkpoint inhibitors (ICI) did not boost antitumor immune responses. Since proteinase inhibitor 9 (PI-9) was detected in tumor cells, a specific inhibitor (PI-9i) was used in addition to ICI in T cell cytotoxicity testing. However, only pre-stimulation with tumor-specific peptides (cryptic and neoantigenic) significantly increased recognition and elimination of tumor cells by T cells independently of ICI or PI-9i. We showed, that ICI resistant tumor cells can be targeted by tumor-primed T cells and also demonstrated the superiority of tumor-naïve peripheral blood T cells compared to highly exhausted tumor-infiltrating T cells. Future precision immunotherapeutic approaches should include multimodal strategies to successfully induce durable anti-tumor immune responses.
Published: 2024
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5. First-in-Human Phase I Trial to Assess the Safety and Immunogenicity of an Orf Virus-Based COVID-19 Vaccine Booster

Author: Meral Esen, Johanna Fischer-Herr, Julian Justin Gabor, Johanna Marika Gaile, Wim Alexander Fleischmann, Geerten Willem Smeenk, Roberta Allgayer de Moraes, Sabine Bélard, Carlos Lamsfus Calle, Tamirat Gebru Woldearegai, Diane Egger-Adam, Verena Haug, Carina Metz, Alena Reguzova, Markus W. Löffler, Baiba Balode, Lars C. Matthies, Michael Ramharter, Ralf Amann, and Peter G. Kremsner
Subjects: Orf virus, viral vector, vaccine, SARS-CoV-2, COVID-19, Parapoxvirus, Medicine
Abstract: The emergence of SARS-CoV-2 has necessitated the development of versatile vaccines capable of addressing evolving variants. Prime-2-CoV_Beta, a novel Orf virus-based COVID-19 vaccine, was developed to express the SARS-CoV-2 spike and nucleocapsid antigens. This first-in-human, phase I, dose-finding clinical trial was conducted to assess the safety, reactogenicity, and immunogenicity of Prime-2-CoV_Beta as a booster in healthy adults. From June 2022 to June 2023, 60 participants in Germany received varying doses of Prime-2-CoV_Beta. The study demonstrated a favorable safety profile, with no serious adverse events (AEs) reported. All AEs were mild (107) or moderate (10), with the most common symptoms being pain at the injection site, fatigue, and headache. Immunogenicity assessments revealed robust vaccine-induced antigen-specific immune responses. High doses notably elicited significant increases in antibodies against the spike and nucleocapsid proteins as well as neutralizing antibodies against SARS-CoV-2 and its variants. Additionally, the vaccine did not induce ORFV-neutralizing antibodies, indicating the potential for repeated administration. In conclusion, Prime-2-CoV_Beta was safe, well tolerated, and immunogenic, demonstrating potential as a broadly protective vaccine against SARS-CoV-2 and its variants. These promising results support further evaluation of higher doses and additional studies to confirm efficacy and long-term protection. This trial was registered at ClinicalTrials, NCT05389319.
Published: 2024
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6. Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency

Author: Jonas S. Heitmann, Claudia Tandler, Maddalena Marconato, Annika Nelde, Timorshah Habibzada, Susanne M. Rittig, Christian M. Tegeler, Yacine Maringer, Simon U. Jaeger, Monika Denk, Marion Richter, Melek T. Oezbek, Karl-Heinz Wiesmüller, Jens Bauer, Jonas Rieth, Marcel Wacker, Sarah M. Schroeder, Naomi Hoenisch Gravel, Jonas Scheid, Melanie Märklin, Annika Henrich, Boris Klimovich, Kim L. Clar, Martina Lutz, Samuel Holzmayer, Sebastian Hörber, Andreas Peter, Christoph Meisner, Imma Fischer, Markus W. Löffler, Caroline Anna Peuker, Stefan Habringer, Thorsten O. Goetze, Elke Jäger, Hans-Georg Rammensee, Helmut R. Salih, and Juliane S. Walz
Subjects: Science
Abstract: Abstract T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469.
Published: 2023
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7. T cells of colorectal cancer patients’ stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells

Author: Peter Bauer, Hans-Georg Rammensee, Nadine Mockel-Tenbrinck, Andrzej Dzionek, Andreas Schlosser, Michael Ghosh, Markus W Löffler, Sandra Schwarz, Johanna Schmitz, Evgenia Olshvang, Marvin Markel, Susann Krake, Basak Arslan, Kapil Dev Kampe, Anne Wendt, Christina S Mullins, and Michael Linnebacher
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc).Methods Colorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients’ Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay.Results 100 tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. The neoantigens originated from single nucleotide substitutions in the genes IQGAP1, CTNNB1, and TRIT1. Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment.Conclusion These results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
Published: 2022
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8. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer

Author: Hans-Georg Rammensee, Karl-Heinz Wiesmüller, P. Anoop Chandran, Henning Zelba, Elisa Rusch, Cécile Gouttefangeas, Daniel J. Kowalewski, Moreno Di Marco, Sebastian P. Haen, Juliane S. Walz, Yamel Cardona Gloria, Johanna Bödder, Jill-Marie Schertel, Antje Tunger, Luise Müller, Maximilian Kießler, Rebekka Wehner, Marc Schmitz, Meike Jakobi, Nicole Schneiderhan-Marra, Reinhild Klein, Karoline Laske, Kerstin Artzner, Linus Backert, Heiko Schuster, Johannes Schwenck, Alexander N. R. Weber, Bernd J. Pichler, Manfred Kneilling, Christian la Fougère, Stephan Forchhammer, Gisela Metzler, Jürgen Bauer, Benjamin Weide, Wilfried Schippert, Stefan Stevanović, and Markus W. Löffler
Subjects: Adjuvant, Lipopeptide, TLR1/2 ligand, Immunotherapy, Vaccines, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide. Case presentation We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood. Conclusion Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.
Published: 2019
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9. Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma

Author: Markus W. Löffler, Christopher Mohr, Leon Bichmann, Lena Katharina Freudenmann, Mathias Walzer, Christopher M. Schroeder, Nico Trautwein, Franz J. Hilke, Raphael S. Zinser, Lena Mühlenbruch, Daniel J. Kowalewski, Heiko Schuster, Marc Sturm, Jakob Matthes, Olaf Riess, Stefan Czemmel, Sven Nahnsen, Ingmar Königsrainer, Karolin Thiel, Silvio Nadalin, Stefan Beckert, Hans Bösmüller, Falko Fend, Ana Velic, Boris Maček, Sebastian P. Haen, Luigi Buonaguro, Oliver Kohlbacher, Stefan Stevanović, Alfred Königsrainer, HEPAVAC Consortium, and Hans-Georg Rammensee
Subjects: Hepatocellular carcinoma, HLA, HLA ligandomics, Immunoinformatics, Immunotherapy, Liver cancer, Medicine, Genetics, QH426-470
Abstract: Abstract Background Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs. Methods In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates. Evidence for the natural presentation of mutated HLA ligands was investigated through an in silico pipeline integrating proteome and HLA ligandome profiling data. Results The approach was successfully validated in a state-of-the-art dataset from malignant melanoma, and despite multi-omics evidence for somatic mutations, mutated naturally presented HLA ligands remained elusive in HCCs. An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations. Conclusions This study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs, inter alia resulting from a low mutational burden as compared to other malignancies such as malignant melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden.
Published: 2019
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10. Aktueller Stand der chirurgischen Therapie peritonealer Metastasen bei kolorektalen Karzinomen

Author: Can Yurttas, Markus W. Löffler, Alfred Königsrainer, and Philipp Horvath
Published: 2022
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11. A Non-interventional Clinical Trial Assessing Immune Responses After Radiofrequency Ablation of Liver Metastases From Colorectal Cancer

Author: Markus W. Löffler, Bianca Nussbaum, Günter Jäger, Philipp S. Jurmeister, Jan Budczies, Philippe L. Pereira, Stephan Clasen, Daniel J. Kowalewski, Lena Mühlenbruch, Ingmar Königsrainer, Stefan Beckert, Ruth Ladurner, Silvia Wagner, Florian Bullinger, Thorben H. Gross, Christopher Schroeder, Bence Sipos, Alfred Königsrainer, Stefan Stevanović, Carsten Denkert, Hans-Georg Rammensee, Cécile Gouttefangeas, and Sebastian P. Haen
Subjects: colorectal cancer, radiofrequency ablation, liver metastasis, HLA ligandome, T cells, tumor-associated antigens, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous in situ tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells. This may explain a phenomenon termed abscopal effect, namely tumor regression in untreated lesions evidenced after distant thermal ablation or irradiation. In this study, we therefore assessed systemic and local immune responses in individual patients treated with RFA.Methods: For this prospective clinical trial, patients with liver metastasis from colorectal carcinoma (mCRC) receiving RFA and undergoing metachronous liver surgery for another lesion were recruited (n = 9) during a 5-year period. Tumor and non-malignant liver tissue samples from six patients were investigated by whole transcriptome sequencing and tandem-mass spectrometry, characterizing naturally presented HLA ligands. Tumor antigen-derived HLA-restricted peptides were selected by different predefined approaches. Further, candidate HLA ligands were manually curated. Peripheral blood mononuclear cells were stimulated in vitro with epitope candidate peptides, and functional T cell responses were assessed by intracellular cytokine staining. Immunohistochemical markers were additionally investigated in surgically resected mCRC from patients treated with (n = 9) or without RFA (n = 7).Results: In all six investigated patients, either induced immune responses and/or pre-existing T cell immunity against the selected targets were observed. Multi-cytokine responses were inter alia directed against known tumor antigens such as cyclin D1 but also against a (predicted) mutation contained in ERBB3. Immunohistochemistry did not show a relevant influx of immune cells into distant malignant lesions after RFA treatment (n = 9) as compared to the surgery only mCRC group (n = 7).Conclusions: Using an individualized approach for target selection, RFA induced and/or boosted T cell responses specific for individual tumor antigens were more frequently detectable as compared to previously published observations with well-characterized tumor antigens. However, the witnessed modest RFA-induced immunological effects alone may not be sufficient for the rejection of established tumors. Therefore, these findings warrant further clinical investigation including the assessment of RFA combination therapies e.g., with immune stimulatory agents, cancer vaccination, and/or immune checkpoint inhibitors.
Published: 2019
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12. Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis

Author: Franziska Herster, Zsofia Bittner, Marius Cosmin Codrea, Nathan K. Archer, Martin Heister, Markus W. Löffler, Simon Heumos, Joanna Wegner, Ramona Businger, Michael Schindler, David Stegner, Knut Schäkel, Stephan Grabbe, Kamran Ghoreschi, Lloyd S. Miller, and Alexander N. R. Weber
Subjects: psoriasis, neutrophil, platelet, platelet-neutrophil complexes (PNCs), imiquimod, Immunologic diseases. Allergy, RC581-607
Abstract: Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.
Published: 2019
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13. Einfluss der Coronapandemie auf die Leberchirurgie und Lebertransplantationen in Deutschland

Author: Can Yurttas, Christina Schleicher, Imma Fischer, Christoph Meisner, Silvio Nadalin, Alfred Königsrainer, Markus W. Löffler, and Markus Quante
Subjects: Surgery
Abstract: Zusammenfassung Hintergrund Die Leberchirurgie ist durch ein hohes perioperatives Risiko und einen großen Ressourcenaufwand geprägt, aber die Operationsindikation ist oftmals alternativlos. Die SARS-CoV-2-Pandemie führte weltweit zu Einschränkungen in der chirurgischen Patientenversorgung und stellte daher auch die Leberchirurgie vor neue Herausforderungen. Welchen Einfluss die Pandemie allerdings auf die Leberchirurgie in Deutschland insgesamt hatte, ist bislang nur unzureichend bekannt. Methoden Auf Basis der durch das Statistische Bundesamt (Destatis) erfassten Daten zu Prozedurenschlüsseln (OPS-Codes) vollstationärer Patienten in Deutschland aus den Jahren 2010–2020 sowie Daten zu Organtransplantationen der Deutschen Stiftung Organtransplantation (DSO) wurde retrospektiv die Anzahl leberchirurgischer Prozeduren in Deutschland zu Beginn der Pandemie mit den Vorjahresdaten sowie mit Zahlen aus dem Eurotransplant-Raum verglichen. Ergebnisse Entsprechend der durch das Statistische Bundesamt dokumentierten Prozedurenschlüssel unterlagen Operationen an der Leber sowie Lebertransplantationen in Deutschland in den Jahren 2010 bis 2020 einer jährlichen Schwankung, die auch im Pandemiejahr 2020, im Gegensatz zu anderen europäischen Ländern, unverändert geblieben ist. Die Entwicklung der postmortalen Lebertransplantation sowie der Leberlebendspenden ist in Deutschland, gemäß den Zahlen der DSO, auch im Jahr 2020 stabil geblieben. Schlussfolgerungen Die Anzahl leberchirurgischer Eingriffe in Deutschland unterlag bis 2020 einer dynamischen Entwicklung, die auch im 1. Pandemiejahr 2020 keine deutliche Veränderung gezeigt hat. Die häufigsten an der Leber durchgeführten Operationen sowie die Lebertransplantation entwickelten sich auch zu Beginn der Pandemie quantitativ weitgehend stabil. Die Veröffentlichung von Daten zu den entsprechenden Prozedurenschlüsseln für das Jahr 2021 bleibt abzuwarten, um die weitere Entwicklung der Leberchirurgie und -transplantation in Deutschland während der SARS-CoV-2-Pandemie beurteilen zu können.
Published: 2022
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14. Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups

Author: Hans-Georg Rammensee, Cécile Gouttefangeas, Sonja Heidu, Reinhild Klein, Beate Preuß, Juliane Sarah Walz, Annika Nelde, Sebastian P. Haen, Michael Reth, Jianying Yang, Ghazaleh Tabatabai, Hans Bösmüller, Helen Hoffmann, Michael Schindler, Oliver Planz, Karl-Heinz Wiesmüller, and Markus W. Löffler
Subjects: peptide vaccine, adjuvant, lipopeptide, high-risk patient, COVID-19, SARS-CoV-2, Medicine
Abstract: We describe the results of two vaccinations of a self-experimenting healthy volunteer with SARS-CoV-2-derived peptides performed in March and April 2020, respectively. The first set of peptides contained eight peptides predicted to bind to the individual’s HLA molecules. The second set consisted of ten peptides predicted to bind promiscuously to several HLA-DR allotypes. The vaccine formulation contained the new TLR 1/2 agonist XS15 and was administered as an emulsion in Montanide as a single subcutaneous injection. Peripheral blood mononuclear cells isolated from blood drawn before and after vaccinations were assessed using Interferon-γ ELISpot assays and intracellular cytokine staining. We detected vaccine-induced CD4 T cell responses against six out of 11 peptides predicted to bind to HLA-DR after 19 days, following vaccination, for one peptide already at day 12. We used these results to support the design of a T-cell-inducing vaccine for application in high-risk patients, with weakened lymphocyte performance. Meanwhile, an according vaccine, incorporating T cell epitopes predominant in convalescents, is undergoing clinical trial testing.
Published: 2021
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15. Integrin activation enables rapid detection of functional Vδ1+and Vδ2+γδ T cells

Author: Nicola Herold, Anna Schöllhorn, Adrian Feile, Andrea Gaißler, Anne Mohrholz, Graham Pawelec, Markus W. Löffler, Stoyan Dimitrov, Cécile Gouttefangeas, and Kilian Wistuba‐Hamprecht
Subjects: Immunology, Immunology and Allergy
Published: 2022
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16. Supplementary Table 6 from Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

Author: Sebastian P. Haen, Stefan Stevanović, Hans-Georg Rammensee, Alfred Königsrainer, Lothar Kanz, Oliver Kohlbacher, Ingmar Königsrainer, Silvia Wagner, Stefan Beckert, Hans-Georg Kopp, Daniel Backes, Florian Dengler, Heiko Schuster, Patrick Adam, Jörg Bernhardt, Linus Backert, Daniel J. Kowalewski, and Markus W. Löffler
Abstract: Statistics over-represented peptides HLA class I
Published: 2023
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17. Supplementary Table 8 from Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

Author: Sebastian P. Haen, Stefan Stevanović, Hans-Georg Rammensee, Alfred Königsrainer, Lothar Kanz, Oliver Kohlbacher, Ingmar Königsrainer, Silvia Wagner, Stefan Beckert, Hans-Georg Kopp, Daniel Backes, Florian Dengler, Heiko Schuster, Patrick Adam, Jörg Bernhardt, Linus Backert, Daniel J. Kowalewski, and Markus W. Löffler
Abstract: Statistics over-represented peptides HLA class II
Published: 2023
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18. Supplementary Tables 1-5, 7, 9-12 from Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

Author: Sebastian P. Haen, Stefan Stevanović, Hans-Georg Rammensee, Alfred Königsrainer, Lothar Kanz, Oliver Kohlbacher, Ingmar Königsrainer, Silvia Wagner, Stefan Beckert, Hans-Georg Kopp, Daniel Backes, Florian Dengler, Heiko Schuster, Patrick Adam, Jörg Bernhardt, Linus Backert, Daniel J. Kowalewski, and Markus W. Löffler
Abstract: Supplementary Tables 1-5, 7, 9-12 containing: Suppl. Table 1: Sample characteristics; Suppl. Table 2: Patient characteristics; Suppl. Table 3: Control peptides Suppl. Table 4: Peptide-specific properties Suppl. Table 5: Over-represented Peptides HLA class I; Suppl. Table 7: Over-represented Peptides HLA class II; Suppl. Table 9: STRING results Suppl. Table 9: Protein-protein interactions (STRING) Suppl. Table 10: Over-represented pathways (STRING) Suppl. Table 11: Vaccine peptide selection Suppl. Table 12: Candidate vaccine peptides
Published: 2023
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19. Data from Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

Author: Sebastian P. Haen, Stefan Stevanović, Hans-Georg Rammensee, Alfred Königsrainer, Lothar Kanz, Oliver Kohlbacher, Ingmar Königsrainer, Silvia Wagner, Stefan Beckert, Hans-Georg Kopp, Daniel Backes, Florian Dengler, Heiko Schuster, Patrick Adam, Jörg Bernhardt, Linus Backert, Daniel J. Kowalewski, and Markus W. Löffler
Abstract: Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma–associated pathways, including Wnt, TGFβ, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627–41. ©2018 AACR.
Published: 2023
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20. Data from Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma

Author: Luigi Buonaguro, Hans-Georg Rammensee, Harpreet Singh-Jasuja, Roberto S. Accolla, Toni Weinschenk, Carsten Reinhardt, Ulrike Gnad-Vogt, Mercedes Iñarrairaegui, Roberta Penta, Caterina Fusco, Maria Tagliamonte, Greta Forlani, Cécile Gouttefangeas, Regina Heidenreich, Tanguy Chaumette, Danila Valmori, Marco Borrelli, Heiko Schuster, Regina Mendrzyk, Katrin Aslan, Christian Flohr, Diego Duarte Alcoba, Jörg Ludwig, Antonio Avallone, Alessandro Inno, Luisa Vonghia, Sven Francque, Bruno Sangro, Yuk Ting Ma, Alfred Königsrainer, Paolo A. Ascierto, Andrea Mayer-Mokler, Francesco Izzo, Stefania Gori, and Markus W. Löffler
Abstract: Purpose:Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response.Patients and Methods:A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints.Results:The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees.Conclusions:Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I– and class II–restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.
Published: 2023
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21. Supplementary Data from Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma

Author: Luigi Buonaguro, Hans-Georg Rammensee, Harpreet Singh-Jasuja, Roberto S. Accolla, Toni Weinschenk, Carsten Reinhardt, Ulrike Gnad-Vogt, Mercedes Iñarrairaegui, Roberta Penta, Caterina Fusco, Maria Tagliamonte, Greta Forlani, Cécile Gouttefangeas, Regina Heidenreich, Tanguy Chaumette, Danila Valmori, Marco Borrelli, Heiko Schuster, Regina Mendrzyk, Katrin Aslan, Christian Flohr, Diego Duarte Alcoba, Jörg Ludwig, Antonio Avallone, Alessandro Inno, Luisa Vonghia, Sven Francque, Bruno Sangro, Yuk Ting Ma, Alfred Königsrainer, Paolo A. Ascierto, Andrea Mayer-Mokler, Francesco Izzo, Stefania Gori, and Markus W. Löffler
Abstract: Supplementary Data from Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma
Published: 2023
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22. Supplementary Figures 1-6 from Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

Author: Sebastian P. Haen, Stefan Stevanović, Hans-Georg Rammensee, Alfred Königsrainer, Lothar Kanz, Oliver Kohlbacher, Ingmar Königsrainer, Silvia Wagner, Stefan Beckert, Hans-Georg Kopp, Daniel Backes, Florian Dengler, Heiko Schuster, Patrick Adam, Jörg Bernhardt, Linus Backert, Daniel J. Kowalewski, and Markus W. Löffler
Abstract: Complete supplementary figures containing: Suppl. Fig. 1: HLA-coverage (Caucasian); Suppl. Fig. 2: Maximum attainable quantities of source proteins; Suppl. Fig. 3: Comparsion with complete benign dataset; Suppl. Fig. 4: Legend PANTHER analysis; Suppl. Fig. 5: Legend KEGG analysis; Suppl. Fig. 6: Representation analysis HLA class II
Published: 2023
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23. A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

Author: Simon Jäger, Juliane S. Walz, Jonas Rieth, Markus W. Löffler, Sebastian Hörber, Reinhild Klein, Julia Karbach, Christoph Meisner, Leonard Anton, Monika Denk, Hans-Georg Rammensee, Annika Nelde, Julia Reusch, Imma Fischer, Lisa Marie Weber, Elke Jäger, Jonas S. Heitmann, Maddalena Marconato, Claudia Tandler, Malte Roerden, Marcel Wacker, Andreas Peter, Jens Bauer, Helmut R. Salih, Marion Richter, Yacine Maringer, and Tatjana Bilich
Subjects: Adult, Male, COVID-19 Vaccines, Adolescent, T cell, T-Lymphocytes, CD8-Positive T-Lymphocytes, Administration, Cutaneous, Article, Peptide vaccines, Interferon-gamma, Young Adult, Clinical Trials, Phase II as Topic, Immunogenicity, Vaccine, Interferon, Phase I trials, Medicine, Humans, B cell, Aged, Aged, 80 and over, Multidisciplinary, Reactogenicity, Granuloma, business.industry, SARS-CoV-2, Immunogenicity, COVID-19, T-Lymphocytes, Helper-Inducer, Middle Aged, Vaccination, medicine.anatomical_structure, Viral infection, Immunology, Vaccines, Subunit, Peptide vaccine, Female, business, CD8, medicine.drug
Abstract: T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18–80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency., A phase I open-label trial evaluating the immunogencity, reactogenicity and safety of a peptide-based SARS-CoV-2 vaccine candidate to induce SARS-CoV-2-specific T cell responses.
Published: 2021

24. NT‐proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials

Author: Stephan B. Felix, Lutz Binder, Kathleen Nolte, Christoph Herrmann-Lingen, Rolf Wachter, Ulrich Laufs, Helge Haarmann, Stefan Gross, Frank T. Edelmann, Gerd Hasenfuß, Christian Becker, Marcus Dörr, Daniela Husser, Meinhard Mende, Martin Scherer, Stefanie Maria Werhahn, Samira Zeynalova, Astrid Petersmann, Nikolaos Dagres, Markus W. Löffler, and Burkert Pieske
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Population, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Natriuretic Peptide, Brain, Outpatients, medicine, Natriuretic peptide, Diseases of the circulatory (Cardiovascular) system, Humans, cardiovascular diseases, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, education, Aged, Heart Failure, education.field_of_study, business.industry, Area under the curve, Atrial fibrillation, Original Articles, Biomarker, Middle Aged, medicine.disease, Brain natriuretic peptide, Peptide Fragments, Population‐based cohort studies, Heart failure, RC666-701, Cardiology, Original Article, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). It is known that AF impairs the diagnostic accuracy of NT‐proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT‐proBNP for HF and AF in stable outpatients with cardiovascular risk factors. Methods and results Data were obtained from the DIAST‐CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population‐based cohorts using the same inclusion/exclusion criteria: LIFE‐Adult (n = 2869), SHIP (n = 2013), and SHIP‐TREND (n = 2408). Serum levels of NT‐proBNP were taken once at baseline. The DIAST‐CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT‐proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT‐proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver‐operating characteristic curves of NT‐proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79–0.88]) and for HF with EF 50% was significantly lower (0.61 [0.56–0.65]) than for AF (P = 0.001). During follow‐up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT‐proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75–0.83]) than of newly diagnosed HF (0.59 [0.55–0.63]; P 50% is very limited.
Published: 2021

25. SARS-CoV-2-Infektionen und klinische Konsequenzen bei organtransplantierten Patienten im Rahmen der ersten Ansteckungswelle in Deutschland - eine monozentrische Umfrage und ein Fallbericht

Author: Linda Brake, Martina Guthoff, Alfred Königsrainer, Helene Haeberle, Silvio Nadalin, Markus W. Löffler, Magdalena Gründl, Christoph P. Berg, Anna Grishina, and Markus Quante
Subjects: Transplantation, Gynecology, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, Surgery, business
Abstract: Zusammenfassung Hintergrund Die SARS-CoV-2-Pandemie hat zu einer globalen Gesundheitskrise mit hohen Mortalitätsraten insbesondere bei Betroffenen in Hochrisikogruppen geführt. Eine stetig wachsende Zahl klinischer Fallberichte zeigt die Folgen von COVID-19 bei Patienten nach solider Organtransplantation (SOT) und deutet auf schwerwiegende klinische Auswirkungen und eine insgesamt hohe Sterblichkeit in dieser Patientengruppe hin. Systematische Daten zu SARS-CoV-2-Infektionen bei SOT-Empfängern in Deutschland fehlten zunächst jedoch weitgehend. Patienten und Methoden Wir führten deshalb eine Umfrage zum SARS-CoV-2-Infektionsstatus unter insgesamt 387 Patienten nach SOT durch, die in den letzten 5 Jahren an unserem Zentrum transplantiert wurden. Die Umfrage wurde 2 Monate nach dem ersten SARS-CoV-2-Ausbruch in unserer relativ stark betroffenen Region und den damit verbundenen staatlich verordneten Einschränkungen durchgeführt. Ergebnisse In unserer SOT-Kohorte wurde eine Rate von 0,4% SARS-CoV-2-positiven Patienten ermittelt, was gut mit den lokalen Infektionsraten in der Allgemeinbevölkerung zum damaligen Zeitpunkt übereinstimmt. Allerdings führte die einzige uns in diesem Kollektiv bekannt gewordene SARS-CoV-2-Infektion zu schwerer Morbidität mit verlängerter mechanischer Beatmung, einem Krankenhausaufenthalt > 60 Tage und resultierte letztlich im irreversiblen Verlust der Transplantatfunktion. Schlussfolgerung Unsere Daten zeigen, dass SOT-Empfänger im Vergleich zur Allgemeinbevölkerung zwar ein vergleichbares Risiko für eine SARS-CoV-2-Infektion haben, diese jedoch mit der Gefahr von schwerwiegenderen Verläufen assoziiert zu sein scheint.
Published: 2021
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26. T cells of colorectal cancer patients' stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells

Author: Sandra Schwarz, Johanna Schmitz, Markus W Löffler, Michael Ghosh, Hans-Georg Rammensee, Evgenia Olshvang, Marvin Markel, Nadine Mockel-Tenbrinck, Andrzej Dzionek, Susann Krake, Basak Arslan, Kapil Dev Kampe, Anne Wendt, Peter Bauer, Christina S Mullins, Andreas Schlosser, and Michael Linnebacher
Subjects: Pharmacology, Cancer Research, Enzyme-Linked Immunospot Assay, Oncology, Immunology, Tumor Microenvironment, Molecular Medicine, Immunology and Allergy, Humans, Antigen-Presenting Cells, Lymphocyte Count, Peptides, Colorectal Neoplasms
Abstract: BackgroundPatients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc).MethodsColorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients’ Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay.Results100 tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. The neoantigens originated from single nucleotide substitutions in the genesIQGAP1, CTNNB1,andTRIT1. Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment.ConclusionThese results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
Published: 2022

27. Establishment of a novel method to assess MEK1/2 inhibition in PBMCs for clinical drug development

Author: Lara M, Schüssele, Julia, Koch-Heier, Julian, Volk, Markus W, Löffler, Katharina, Hoffmann, Regina M, Bruyns, and Oliver, Planz
Abstract: The Raf/MEK/ERK signaling pathway plays a key role in regulating cellular proliferation, differentiation, apoptosis, cytokine production, and immune responses. However, it is also involved in diseases such as cancer, and numerous viruses rely on an active Raf/MEK/ERK pathway for propagation. This pathway, and particularly MEK1/2, are therefore promising therapeutic targets. Assessment of target engagement is crucial to determine pharmacodynamics or the efficacy of a MEK1/2 inhibitor. In the field of infectious diseases, this is usually first determined in clinical trials with healthy volunteers. One method to detect MEK1/2 inhibitor target engagement is to assess the degree of ERK1/2 phosphorylation, as ERK1/2 is the only known substrate of MEK1/2. As healthy subjects, however, only feature a low baseline MEK1/2 activation and therefore low ERK1/2 phosphorylation in most tissues, assessing target engagement is challenging, and robust methods are urgently needed. We hence developed a method using PBMCs isolated from whole blood of healthy blood donors, followed by
Published: 2022

28. A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

Author: Alfred Königsrainer, Can Yurttas, Markus W. Löffler, Stefan Beckert, Philipp Horvath, Christoph Meisner, Imma Fischer, Ingmar Königsrainer, and Silvio Nadalin
Subjects: Peritoneal Surface Malignancy, medicine.medical_specialty, Pilot Projects, Hyperthermic Intraperitoneal Chemotherapy, Adenocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Adverse effect, Peritoneal Neoplasms, Body surface area, business.industry, Mortality rate, Cytoreduction Surgical Procedures, medicine.disease, Combined Modality Therapy, Gemcitabine, Surgery, Pancreatic Neoplasms, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, Pancreas, business, medicine.drug
Abstract: Background Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery. Methods This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m2 body surface area heated to 42 °C for 1 hour. Results Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk. Conclusion Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified. Registration Number NCT02863471 (http://www.clinicaltrials.gov).
Published: 2021

29. [Impact of the SARS-CoV-2 Pandemic on Liver Surgery and Liver Transplantations in Germany]

Author: Can, Yurttas, Christina, Schleicher, Imma, Fischer, Christoph, Meisner, Silvio, Nadalin, Alfred, Königsrainer, Markus W, Löffler, and Markus, Quante
Subjects: Liver, SARS-CoV-2, Germany, COVID-19, Humans, Pandemics, Liver Transplantation, Retrospective Studies
Abstract: The SARS-CoV-2 pandemic has led to restrictions in surgical care worldwide and therefore also posed new challenges to liver surgery. The respective procedures often entail high perioperative risks and resource requirements. However, the indication for liver surgery is frequently without alternatives. To date, there is little knowledge about the impact of the pandemic on liver surgery in Germany.A retrospective data analysis of liver surgery procedures in Germany as well as transplantations was conducted. Evaluations were based on procedure codes recorded between 2010 and 2020 according to diagnosis-related groups (DRG) by the Federal Statistical Office of Germany (Destatis) and data from the German Organ Procurement Organization (Deutsche Stiftung Organtransplantation; DSO).According to DRG procedure codes relating to liver surgery recorded between 2010 and 2020 in Germany, the annual fluctuation for the first year of the pandemic 2020 remained comparable to previous years. Furthermore, the development of post-mortem liver transplantations as well as living liver donations remained stable in Germany in 2020 and 2021.The number of liver surgery procedures in Germany was subject to a dynamic development until 2020, without apparent changes in the first year of the SARS-CoV-2 pandemic. The most frequently performed liver procedures, as well as liver transplantations, remained stable with respect to their annually recorded numbers. Publication of data regarding procedures in liver surgery and transplantation in 2021 need to be awaited and analyzed to evaluate whether the observations presented in this article prove stable any further.Die Leberchirurgie ist durch ein hohes perioperatives Risiko und einen großen Ressourcenaufwand geprägt, aber die Operationsindikation ist oftmals alternativlos. Die SARS-CoV-2-Pandemie führte weltweit zu Einschränkungen in der chirurgischen Patientenversorgung und stellte daher auch die Leberchirurgie vor neue Herausforderungen. Welchen Einfluss die Pandemie allerdings auf die Leberchirurgie in Deutschland insgesamt hatte, ist bislang nur unzureichend bekannt.Auf Basis der durch das Statistische Bundesamt (Destatis) erfassten Daten zu Prozedurenschlüsseln (OPS-Codes) vollstationärer Patienten in Deutschland aus den Jahren 2010–2020 sowie Daten zu Organtransplantationen der Deutschen Stiftung Organtransplantation (DSO) wurde retrospektiv die Anzahl leberchirurgischer Prozeduren in Deutschland zu Beginn der Pandemie mit den Vorjahresdaten sowie mit Zahlen aus dem Eurotransplant-Raum verglichen.Entsprechend der durch das Statistische Bundesamt dokumentierten Prozedurenschlüssel unterlagen Operationen an der Leber sowie Lebertransplantationen in Deutschland in den Jahren 2010 bis 2020 einer jährlichen Schwankung, die auch im Pandemiejahr 2020, im Gegensatz zu anderen europäischen Ländern, unverändert geblieben ist. Die Entwicklung der postmortalen Lebertransplantation sowie der Leberlebendspenden ist in Deutschland, gemäß den Zahlen der DSO, auch im Jahr 2020 stabil geblieben.Die Anzahl leberchirurgischer Eingriffe in Deutschland unterlag bis 2020 einer dynamischen Entwicklung, die auch im 1. Pandemiejahr 2020 keine deutliche Veränderung gezeigt hat. Die häufigsten an der Leber durchgeführten Operationen sowie die Lebertransplantation entwickelten sich auch zu Beginn der Pandemie quantitativ weitgehend stabil. Die Veröffentlichung von Daten zu den entsprechenden Prozedurenschlüsseln für das Jahr 2021 bleibt abzuwarten, um die weitere Entwicklung der Leberchirurgie und -transplantation in Deutschland während der SARS-CoV-2-Pandemie beurteilen zu können.
Published: 2022

30. [Current status of surgical treatment of peritoneal metastases from colorectal cancer]

Author: Can, Yurttas, Markus W, Löffler, Alfred, Königsrainer, and Philipp, Horvath
Subjects: Oxaliplatin, Humans, Hyperthermia, Induced, Colorectal Neoplasms, Combined Modality Therapy, Peritoneal Neoplasms
Abstract: Cytoreductive surgery, often in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), has been instrumental in improving the survival of patients with peritoneal metastases from colorectal cancer. Recent studies have highlighted the benefits of complete cytoreduction, while the role of the HIPEC treatment remains unclear. An oxaliplatin-based HIPEC over 30 min could not achieve any clear benefits in studies on colorectal cancer, neither in the therapeutic nor in the prophylactic setting, but caused relevant side effects and increased the morbidity. The negative results of these studies with respect to oxaliplatin-based HIPEC require critical appraisal; however, they should by no means be regarded as a general setback for surgical treatment of peritoneal metastases and be misunderstood as a general failure of this treatment. While HIPEC after complete surgical cytoreduction of peritoneal metastases from colorectal cancer requires further research, cytoreductive surgery should still be regarded as a highly effective treatment for suitable patients with limited abdominal tumor dissemination.Die zytoreduktive Chirurgie, vielfach in Kombination mit einer hyperthermen intraperitonealen Chemotherapie (HIPEC), hat maßgeblich zur Verbesserung des Überlebens von Patientinnen und Patienten mit peritonealen Metastasen kolorektaler Karzinome beigetragen. Während für den Nutzen einer vollständigen Zytoreduktion klare Belege existieren, ist der Stellenwert der HIPEC-Behandlung ungeklärt. Eine Oxaliplatin-haltige HIPEC über 30 min war in Studien bei kolorektalen Karzinomen weder in therapeutischer noch in prophylaktischer Indikation klar von Vorteil, verursachte aber relevante Nebenwirkungen und steigerte die Morbidität. Die negativen Ergebnisse dieser Studien in Bezug auf die Oxaliplatin-haltige HIPEC erfordern eine kritische Betrachtung. Sie dürfen aber keinesfalls als allgemeiner Rückschlag für die chirurgische Therapie peritonealer Metastasen missverstanden werden. Während die HIPEC nach einer kompletten chirurgischen Zytoreduktion peritonealer Metastasen kolorektaler Karzinome weiterer Erforschung bedarf, kann die zytoreduktive Chirurgie als hocheffektive Therapie für geeignete Patienten mit einer begrenzten abdominellen Tumoraussaat gelten.
Published: 2022

31. Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

Author: Dmitri Nepogodiev, Joana Ff Simoes, Elizabeth Li, Maria Picciochi, James C Glasbey, Glauco Baiocchi, Ruth Blanco-Colino, Daoud Chaudhry, Ehab AlAmeer, Kariem El-Boghdadly, Funmilola Wuraola, Dhruva Ghosh, Rohan R Gujjuri, Ewen M Harrison, Herman Lule, Haytham Kaafarani, Mohammad Khosravi, Irmgard Kronberger, Sezai Leventoğlu, Harvinder Mann, Kenneth A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin Ntirenganya, Lisa Norman, Oumaima Outani, Riinu Pius, Peter Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei Satoi, Catherine Shaw, Aneel Bhangu, Omar M Omar, Waheed-Ul-Rahman Ahmed, Leah Argus, Alasdair Ball, Edward P Bywater, Amanpreet Brar, Brett E Dawson, Irani Duran, Muhammed Elhadi, Conor S Jones, Sivesh K Kamarajah, James M Keatley, Samuel Lawday, Ella J Marson, Riinu Ots, Irène Santos, Elliott H Taylor, Isobel M Trout, Chris Varghese, Mary L Venn, William Xu, Irida Dajti, Arben Gjata, Salah Eddine Oussama Kacimi, Luis Boccalatte, Daniel Cox, Philip Townend, Felix Aigner, Irmgard Elisabeth Kronberger, Elgun Samadov, Amer Alderazi, Kamral Hossain, Greg Padmore, Gabrielle van Ramshorst, Ismaïl Lawani, Anis Cerovac, Samir Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad Gohar, Mihail Slavchev, Chukwuemeka Nwegbu, Arnav Agarwal, Janet Martin, Joshua Ng-Kamstra, Maricarmen Olivos, Wenhui Lou, Dong-Lin Ren, Jose Andres Calvache, Carlos J Perez Rivera, Ana Danic Hadzibegovic, Tomislav Kopjar, Jakov Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos Gouvas, Jaroslav Klat, René Novysedlák, Nicolas Amisi, Peter Christensen, Alaa El-Hussuna, Sylvia Batista, Eddy Lincango-Naranjo, Sameh Emile, Danilo Alfonso Arévalo Sandoval, Hailu Dhufera, Samuel Hailu, Mengistu G Mengesha, Joonas H Kauppila, Alexis P Arnaud, Zaza Demetrashvili, Markus Albertsmeier, Hans Lederhuber, Markus W Löffler, Daniel Kwesi Acquah, Bernard Ofori, Stephen Tabiri, Symeon Metallidis, Georgios Tsoulfas, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Tamás Mersich, Dániel Wettstein, Gabriele Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud Mozafari, Ahmed Hilmi, Helen Mohan, Oded Zmora, Gaetano Gallo, Francesco Pata, Gianluca Pellino, Yuki Fujimoto, Naoto Kuroda, Mohamad K Abou Chaar, Faris Ayasra, Ildar Fakhradiyev, Intisar Hisham Said Hamdun, Jang Jin-Young, Mohammad Jamal, Lina Karout, Aiste Gulla, Fanjandrainy Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura Martinez, María José Martínez, Alejandra Nayen, Antonio Ramos-De la Medina, Jade Nunez, Pueya Rashid Nashidengo, Rakesh Shah, Ashish Lal Shrestha, Pascal Jonker, Schelto Kruijff, Milou Noltes, Pieter Steinkamp, Deborah Wright, Lukman Abdur-Rahman, Adesoji Ademuyiwa, Adewale Adisa, Babatunde Osinaike, Justina Seyi-Olajide, Omolara Williams, Emmanuel Williams, Sofija Pejkova, Zainab Al Balushi, Raza Sayyed, Mustafa Abo Mohsen, Sadi A Abukhalaf, Moises Cukier, Hugo Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr Major, José Azevedo, Miguel F Cunha, Ahmad Zarour, Eduard-Alexandru Bonci, Ionut Negoi, Sergey Efetov, Viktor Kochetkov, Andrey Litvin, Jc Allen Ingabire, Georges Bucyibaruta, Ntirenganya Faustin, Sosthene Habumuremyi, Alphonsine Imanishimwe, Haragirimana Jean de Dieu, Emmanuel Munyaneza, Isaie Ncogoza, Ehab Alameer, Abdourahmane Ndong, Dejan Radenkovic, Min Hoe Chew, Frederick Koh, James Ngu, Arpád Panyko, Uros Bele, Jurij Aleš Košir, Hassan Daoud, Ana Maria Minaya Bravo, Umesh Jayarajah, Dakshitha Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin Rutegård, Malin Sund, Michel Adamina, Eleftherios Gialamas, Karoline Horisberger, Muhammad Alshaar, Abel Huang, Varut Lohsiriwat, Shane Charles, Haithem Jlassi, Arda Isik, Hervé Monka Lekuya, Slava Kopetskyi, Hayder Alsaadi, Sattar Alshryda, Osaid Alser, Brittany Bankhead-Kendall, Kerry Breen, Hassan Mashbari, Fernando Bonilla Cal, Hamza Al-Naggar, Mayaba Maimbo, Dennis Mazingi, 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Diana Alejandra Pantoja Pachajoa, Agustin Duro, José Alfredo Calderón Arancibia, Giuliana D'Aulerio, Nagendra Dudi-Venkata, Natasha Egoroff, Shebani Farik, Natalie Lott, Jana-Lee Moss, Sarah Rennie, Lorwai Tan, Uyen Giao Vo, David Watson, David Watters, Tim Bright, Paul Hollington, Xuanyu Zhou, Hidde M Kroon, Anthony Farfus, John Barker, Eleanor Watson, Sean Stevens, Haider Latif, Amanda Caroline Dawson, Alwin Chuan, Vijayaragavan Muralidharan, Enoch Wong, Travis Ackermann, Maurizio Pacilli, Russell Hodgson, Alexander Heriot, Peter Choong, Wendy Brown, Surjit Lidder, Justin Yeung, Luke Traeger, Guillermo Regalo, Ralph Gourlay, Sarit Badiani, Cherry Koh, Soni Putnis, Fayza Haider, Ashrarur Rahman Mitul, Niels Komen, Bert Dhondt, Serge Cappeliez, Manon Pigeolet, Martijn Schoneveld, Jasper Stijns, Wouter Oosterlinck, Nicolas Flamey, Cyrille Kpangon, Mouhamed Agbadebo, S Mèvo Romaric Tobome, Aldo Vieira Barros, Samuel Aguiar Júnior, Heloisa Galvão do Amaral Campos, Jefferson Gross, Felipe 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Montenegro, Julia Rodriguez-Abreu, Dolores Mejía, Galal Abouelnagah, Sameh Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy A Hassan, Mahmoud M Saad, Mohamed Reda Loaloa, Badr Mostafa, Mohamed Qassem, Mohamed Fahmy, Hesham Abozied, Ahmed Y Azzam, Sherief Ghozy, Asser Sallam, Ahmed Shehta, Mohamed Abdelkhalek, Rehab Samaka, Amr Morsy, Ahmed Elshawadfy Sherif, Abraham Negussie, Tigist Fisseha, Kibruyisfaw Shumbash, Metasebia Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe Megersa, Teshome Tefera, Melatework Assefa, Bahru Atnafu, Bereket Tsegaye, Yoseph Solomon Bezabih, Silamlak Sisay, Kebebe Bekele, Moa Jira, Habtamu Derilo, Eyueal Degefa, Anteneh Tadesse, Melkamu Nidaw, Elise Sarjanoja, Sylvie Testelin, Sophie Boucher, Lionel Jouffret, Zaher Lakkis, Alban Zarzavadjian Le Bian, Luke Harper, Marc Danguy des Déserts, Benoît André, Karem Slim, Romain Verhaeghe, Andrea Police, Edouard Girard, Alexandre Chebaro, Armande Subayi Nkembi, Laurent Arnalsteen, Quentin Ballouhey, Diane 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Eleonora Gut, Jens Gempt, Daniel Reim, Arthur Wagner, Alexander M Keppler, Mircea Gabriel Stoleriu, Tim Saier, Josef Stadler, Julia Christina Kaiser, Stefan M Brunner, Karin Pfister, Jonas Herzberg, Kai Nowak, Tobias Reinhard, Gregor A Stavrou, Alfred Königsrainer, Christian Konrads, Markus Quante, Simon Laban, Silke von Pusch, Markus Hirschburger, Johannes Doerner, Armin Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra Rodas, Ana Lucía Portilla, Jacqueline Carrera, Amalia Barrios Duarte, Megan Lowey, Sabrina Barillas, Atul Suroy, Dhaivat Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa Madabhavi, Dhananjaya Bhat, Sunil Kumar Venkatappa, Sumit Thakar, Kavitha Jain, Aruna Kumar, Manoj Nagar, Tushar Mishra, Arunkumar Sekar, Anand Gupta, Lileswar Kaman, Madhivanan Karthigeyan, Manjul Tripathi, Ashwin Rammohan, Sudheer Othiyil Vayoth, Anupama Rajanbabu, Anbukkani Subbian, Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, 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Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, Muhammad Fahadullah, Éanna Ryan, Tara Connelly, Oded Zmora, Daisuke Hashimoto, Majdi Ali Alqudah, Amer Alajalen, Rand Y Omari, Faris Ayasra, Abdulrahman Qasem, Yazan Alawneh, Amer Ahmad, Omar Aladawi, Bourhan Alrayes, Hanan Haidar, Shatha Husain, Faisal Qassem, Adnan Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid Alsunna, Hazim Ra'ed, Faten Reyad Bani Hamad, Amro Abuleil, Mohamad K Abou Chaar, Elmi Ahmed Mohamed Jimaale, Marah Abu-Mehsen, Noor Olaywah, Omar Wafi, Hazim Ababneh, Luai Abu-Ismail, Almu'atasim Khamees, Ahmad Alkhatib, Raikhan Bolatbekova, Mukhtar Kulimbet, Talgat Nurgozhin, Timur Saliev, Baurzhan Zhussupov, Ydyrys Almabayev, Ildar Fakhradiyev, Timur Saliev, Dilyara Kaidarova, Khalil Tamoos, Ahmed Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah Alkadeeki, Milad Gahwagi, Wafa Aldressi, Mohamed Amnaina, Arowa Hassan Abdulrahman Alansari, Akram Alkaseek, Ghozlan Yagoub, Anass Ben Amer, Marwa Salem, Ayman Almugaddami, Dania Burgan, Mohammed Abdelkabir, Khayriyah Alshareef, Rayet Al Islam Ben Jouira, Ayman Meelad, Ahmad Bouhuwaish, Sumayya Essayah Dwaga, Houda Khalifa, Bushray Almiqlash, Taha Suliaman, Mohammed Alawami, Fras Elhajdawe, Hajir Aboazamazem, Ibrahim Ellojli, Ahmed Msherghi, Ismail Ali Saleh, Mohammed Alayan, April Camilla Roslani, Marcel Didier Ndayishyigikiye, Akutu Munyika, Philipp Plarre, David W Borowski, Pueya Rashid Nashidengo, Milou Noltes, Pieter Steinkamp, Cameron Wells, Rebecca Teague, Brodie Elliott, David Kieser, Omar Mohyieldin, Chris Varghese, Nick McIntosh, Cheyaanthan Haran, Sarah Rennie, Jasmin King, Jeong Ha, Matthew James McGuinness, Opeoluwa Adesanya, Julius Olaogun, Akinola Akinmade, Kefas Bwala, Peter Agbonrofo, Akinwale Afolabi, Usang Usang, Sebastian Ekenze, Samson Olori, Taiwo Akeem Lawal, Justina Seyi-Olajide, Abiodun Okunlola, Omolara Williams, Adewale Adisa, Lukman Abdur-Rahman, Stephen 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Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Marie Dione Sacdalan, Piotr Major, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, José Azevedo, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, Miguel F Cunha, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Ahmad Zarour, Ahmad Zarour, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Ionut Negoi, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Eduard-Alexandru Bonci, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Andrey Litvin, Vadim Pykhteev, Marianna Raevskaya, Sergey Efetov, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Azah Althumairi, Mohammad Alyami, Abdulrahman Al Amri, Azah Althumairi, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Abdourahmane Ndong, Jacques Tendeng, Nan Zun Teo, Frederick Koh, Jurij Aleš Košir, Uros Bele, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Jorge Nuñez, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Ana Maria Minaya Bravo, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Umesh Jayarajah, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Dakshitha Wickramasinghe, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Eleftherios Gialamas, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Arda Isik, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Hervé Monka Lekuya, Ronald Kiweewa, Herman Lule, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Sattar Alshryda, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Mohamed Mashhour, Mohamed Mashhour, Antony Louis Rex Michael, Hayder Alsaadi, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Sivesh K Kamarajah, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Grant D Stewart, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Kariem El-Boghdadly, Cyrus Kerawala, Chetan Parmar, Tom Abbott, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, John Edwards, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Joseph Incorvia, Sameer Hirji, Matthew Naunheim, Frederick Drake, Haytham Kaafarani, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Henry E Rice, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Brittany Bankhead-Kendall, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Hamza Al-Naggar, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Ervis Agastra, Enton Bollano, Kostandin Gjyli, Dariel Thereska, Irida Dajti, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Veronica Laudani, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Luis Boccalatte, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, Ricardo Esteban Mentz, Pedro Mercado, Pablo Moyano, Florencia Noll, Diego Odetto, Agustina Rene Oliva, Rafael Perez Vidal, Catalina Poggi, Eduardo Jorge Premoli, María Lourdes Ramos, Patricio Rosas, Luciano Rossi, Gustavo Rossi, Jose Saadi, Jordán Scherñuk, Pablo Slullitel, María Verona Stang, María Victoria Taboada, Sebastian Tirapegui, Constanza Uffelmann, Carlos Vaccaro, Roberto Vagni, Ana Clara Valerio, Celeste Soledad Zarratea, Carina Chwat, Silvina Montal, Brian Morris, Pedro Valdez, Fernando Diaz-Couselo,Ricci C, Casadei R, Fruscio, R, Ornaghi, S, Felice Pecoraro, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Vito Chiantera, Mariano Catello Di Donna, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Simoes, J, Rosati, R, on behalf of COVIDSurg Collaborative, GlobalSurg Collaborative, Aldrighetti, L, Mortini, P, Olmi, S, Medical Oncology, Assoc Surg Training ASiT, European Soc Coloproctology ESCP, EuroSurg, G4 Alliance, GlobalPaedSurg, GICS, ItSURG, ISRC, Italian Soc Colorectal Surg SICCR, PTSurg, S-ECCO, South African Soc, and SpainSurg
Subjects: Lung Diseases, Male, Internationality, SARS-Cov-2, COVID-19, surgery, pathways, pre-operative isolation, Settore MED/18 - CHIRURGIA GENERALE, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Lung Disease, ESTUDOS PROSPECTIVOS, Cohort Studies, Patient Isolation, Postoperative Complications, 80 and over, Prospective Studies, Prospective cohort study, 610 Medicine & health, Aged, 80 and over, Incidence (epidemiology), Treatment Outcome, Elective Surgical Procedures, Female, Elective Surgical Procedure, Cohort study, Human, medicine.medical_specialty, Isolation (health care), Preoperative care, NO, Anesthesiology, Preoperative Care, medicine, Humans, Elective surgery, LS7_4, Aged, business.industry, pathway, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Prospective Studie, Anesthesiology and Pain Medicine, Human medicine, Postoperative Complication, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.
Published: 2021
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32. Gaia Early Data Release 3 The Gaia Catalogue of Nearby Stars

Author: Zoltan Balog, G. Tauran, Vincenzo Ripepi, Gerry Gilmore, M. Barros, Łukasz Wyrzykowski, Alberto Cellino, E. Poggio, P. Gavras, Simchon Faigler, Marc Audard, C. Nicolas, M. Vaillant, A. Mora, Paolo Tanga, Silvio Leccia, Despina Hatzidimitriou, A. Dapergolas, Eva Sciacca, Alberto Krone-Martins, N. Cheek, M. Hauser, Ulrike Heiter, S. Managau, L. Rohrbasser, Mathias Schultheis, E. Utrilla, Minia Manteiga, Marcella Marconi, Xavier Luri, F. De Angeli, Shay Zucker, Paolo Giacobbe, J. Juaristi Campillo, H. I. Siddiqui, J. Torra, F. X. Pineau, Roy Gomel, Thierry Morel, T. Cornez, Eric Gosset, Mario Gai, Jose M Hernandez, G. Giuffrida, A. de Torres, Laszlo Szabados, S. Ragaini, E. van Dillen, D. Semeux, Leanne P. Guy, R. Drimmel, L. M. Sarro, S. Voutsinas, Johannes Sahlmann, Damien Ségransan, S. Liao, Derek W. Morris, Jan Rybizki, André Moitinho, T. Roegiers, Bengt Edvardsson, Tristan Cantat-Gaudin, Martin Altmann, C. Turon, Laurent Chemin, K. Janßen, D. Garabato, Alejandra Recio-Blanco, Michał Pawlak, Lorenzo Rimoldini, Sergei A. Klioner, F. Torra, Carine Babusiaux, Alfred Castro-Ginard, G. Plum, Mariateresa Crosta, Iain A. Steele, A. Yoldas, Alex Lobel, J.-L. Bassilana, Harry Enke, Rosanna Sordo, Francesca Fragkoudi, F. De Luise, M. Bernet, Alessandro Sozzetti, M. Kontizas, Roberto Molinaro, C. Diener, S. Regibo, D. Barbato, T. Pauwels, R. E. de Souza, C. Fabricius, D. Souami, L. Martin Polo, M. Ramos-Lerate, Douglas J. Marshall, A. G. Butkevich, P. Madrero Pardo, P. Re Fiorentin, J. F. Le Campion, Jérôme Berthier, N. Tonello, Ummi Abbas, Y. Lebreton, M. Biermann, D. Munoz, N. Brouillet, David Teyssier, O. Vanel, P. A. Palicio, A. Jean-Antoine Piccolo, A. F. Lanza, Jesus Salgado, E. del Pozo, Antti Penttilä, R. Geyer, Ramachrisna Teixeira, L. Chaoul, Mike Smith, Rossella Cancelliere, J. M. Martín-Fleitas, D. Baines, M. Romero-Gómez, E. Anglada Varela, E. Livanou, X. Peñalosa Esteller, S. Diakite, Alberto Vecchiato, Thomas Wevers, Daniel Hestroffer, Sebastian L. Hidalgo, M. David, Angela Bragaglia, J. De Ridder, Mark Taylor, Roberto Morbidelli, A. Sagristà Sellés, Nigel Hambly, Arnaud Siebert, R. L. Smart, P. Burgess, Y. Le Fustec, Alessandro Bressan, H. Steidelmüller, Alberto Riva, H. E. Huckle, Morgan Fouesneau, N. Bauchet, P. Osborne, S. Marinoni, Krzysztof A. Rybicki, A. Masip, Laia Casamiquela, R. Messineo, A. Garofalo, Antonella Vallenari, R. Mor, Sahar Shahaf, P. de Laverny, G. Sadowski, Peter G. Jonker, A. Kochoska, F. Taris, A. F. Mulone, M. Ajaj, C. Ducourant, T. A. Lister, F. A. Jansen, Ruth Carballo, J. M. Carrasco, Tatiana Muraveva, W. van Reeven, P. Sartoretti, Jordi Portell, Andreas Korn, E. Salguero, Ana Ulla, P. Di Matteo, Coryn A. L. Bailer-Jones, J. Bakker, F. Riclet, G. Altavilla, Ulrich Bastian, P. Esquej, R. Buzzi, M. Segol, A. C. Lanzafame, L. Balaguer-Núñez, Beatrice Bucciarelli, C. Panem, E. Balbinot, T. Carlucci, Davide Massari, P. de Teodoro, Sébastien Lambert, M. I. Carnerero, Amina Helmi, F. Solitro, C. Robin, Carlos Dafonte, Tsevi Mazeh, A. Panahi, C. Fabre, Sergi Blanco-Cuaresma, Deborah Busonero, Maroussia Roelens, O. Marchal, Tomaz Zwitter, B. Holl, G. Holland, William Thuillot, Michael Davidson, E. Licata, Michele Bellazzini, Teresa Antoja, E. Szegedi-Elek, Francesca Figueras, Eric Slezak, Sergio Messina, N. Samaras, E. Poujoulet, Mark Cropper, A. Burlacu, R. Blomme, Elmé Breedt, Annie C. Robin, H. E. Delgado, Z. Kostrzewa-Rutkowska, Georges Kordopatis, Conny Aerts, L. Noval, Daniel Michalik, P. J. Richards, L. Karbevska, Grigori Fedorets, Maria Süveges, F. Crifo, J. Guiraud, D. Eappachen, K. Kruszyńska, Gisella Clementini, P. Yvard, Carme Jordi, L. Bramante, G. Busso, P. David, E. Fraile, Ugo Becciani, A. Lorca, Sanjeev Khanna, Alex Bombrun, Isabella Pagano, C. Dolding, A. M. Piersimoni, Paolo Montegriffo, A. Abreu Aramburu, Anthony G. A. Brown, Simon Hodgkin, Ennio Poretti, M. Fabrizio, I. Gonzalez-Santamaria, N. A. Walton, P. Panuzzo, Benoit Carry, Raphael Guerra, J. J. González-Vidal, T. Lebzelter, Nami Mowlavi, C. Barache, M. M. S. Marcos Santos, S. Cowell, Marco Castellani, J. J. Aguado, N. R. Millar, A. Baudesson-Stella, N. Leclerc, S. Bartolomé, J. Álvarez Cid-Fuentes, F. van Leeuwen, S. Bouquillon, Uwe Lammers, D. W. Evans, L. Eyer, M. van Leeuwen, A. Guerrier, J. González-Núñez, H. E. P. Lindstrøm, Miguel García-Torres, Ilaria Musella, L. Palaversa, W. Roux, W. Löffler, J.-B. Delisle, Dimitri Pourbaix, Timo Prusti, J. Osinde, M. Riello, G. Orrù, C. Crowley, Alessandra Mastrobuono-Battisti, Hector Canovas, D. L. Harrison, Y. Lasne, E. F. del Peloso, Laurent Galluccio, N. Hładczuk, T. Boch, Martin A. Barstow, László Molnár, Aldo Dell'Oro, C. Pagani, Krzysztof Nienartowicz, Stefano Bertone, Patrick Charlot, Eduard Masana, Elisabetta Caffau, N. Robichon, Luciana Bianchi, Federica Spoto, Felix Franke, J. L. Halbwachs, R. Gutiérrez-Sánchez, L. Pulone, Yassine Damerdji, Frédéric Arenou, Richard I. Anderson, Elena Pancino, David Hobbs, P. Castro Sampol, Yves Fremat, Pierre Kervella, C. Zurbach, Sofia Randich, Robert G. Mann, J. C. Segovia, Diego Bossini, D. Katz, Nicholas Rowell, P. Ramos, E. Racero, G. Gracia-Abril, R. Santoveña, R. Haigron, N. Unger, Enrique Solano, S. G. Baker, W. J. Cooper, F. Royer, S. Accart, George M. Seabroke, João Alves, Emese Plachy, Thomas Hilger, Pedro García-Lario, Gérard Jasniewicz, Kevin Benson, Christos Siopis, J. Souchay, Agnes Fienga, Giovanni Comoretto, F. Julbe, A. Hutton, Pierre Fernique, Céline Reylé, F. Pailler, Stefan Jordan, J. H. J. de Bruijne, C. A. Stephenson, E. Gerlach, Elisa Distefano, Karri Muinonen, Y. Viala, H. Zhao, L. Siltala, C. P. Murphy, Maria-Rosa L. Cioni, Andrea Chiavassa, D. Molina, J. Fernández-Hernández, G. Jevardat de Fombelle, Federico Marocco, Nicoletta Sanna, Alexey Mints, Juan Zorec, Ángel Gómez, I. Bellas-Velidis, M. G. Lattanzi, C. M. Raiteri, E. Brugaletta, Mikael Granvik, O. L. Creevey, Guy Rixon, Francois Mignard, P. M. Marrese, M. A. Álvarez, Caroline Soubiran, Rene Andrae, C. Ordénovic, A. Delgado, V. Sanchez Gimenez, J. Castañeda, D. Vicente, R. De March, A. Garcia-Gutierrez, M. Weiler, F. Thévenin, Lennart Lindegren, Isabelle Lecoeur-Taïbi, Jon Marchant, Monica Rainer, Alessandro Spagna, Andrej Prsa, M. Sarasso, Nicolas Rambaux, Paul J. McMillan, Ludovic Delchambre, M. Garcia-Reinaldos, M. Haywood, C. Fouron, S. Girona, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Universidad de Barcelona, Xunta de Galicia, Generalitat de Catalunya, INAF - Osservatorio Astrofisico di Torino (OATo), Istituto Nazionale di Astrofisica (INAF), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Joseph Louis LAGRANGE (LAGRANGE), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National d'Études Spatiales [Toulouse] (CNES), Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Astronomische Rechen-Institut [Heidelberg] (ARI), Zentrum für Astronomie der Universität Heidelberg (ZAH), Universität Heidelberg [Heidelberg]-Universität Heidelberg [Heidelberg], Systèmes de Référence Temps Espace (SYRTE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Observatoire astronomique de Strasbourg (ObAS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Mésocentre de calcul (MESOCENTRE), Université de Franche-Comté (UFC), Centre de Données Astronomiques de Strasbourg, Partenaires INRAE, Géoazur (GEOAZUR 7329), Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratoire Univers et Particules de Montpellier (LUPM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Montpellier 2 - Sciences et Techniques (UM2), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), THALES, Université de Namur [Namur] (UNamur), Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University-Universität Heidelberg [Heidelberg] = Heidelberg University, Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), THALES [France], Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Cantabria, Gaia Collaboration, Planetary-system research, Department of Physics, Particle Physics and Astrophysics, Astronomy, and ITA
Subjects: trigonometric parallaxes, Solar neighborhood, Stars: luminosity function, mass function, Astronomy, Astrophysics, 01 natural sciences, luminosity function, mass function [Stars], Astronomi, astrofysik och kosmologi, luminosity: mass function [Stars], Astronomy, Astrophysics and Cosmology, MAIN-SEQUENCE, Hertzsprung-Russell-diagram, 010303 astronomy & astrophysics, Stars:low-mass brown-dwarfs, wide binaries, Physics, education.field_of_study, north galactic pole, Astrophysics::Instrumentation and Methods for Astrophysics, Astrometry, BROWN DWARF, Astrophysics - Solar and Stellar Astrophysics, mass function, NORTH GALACTIC POLE, Physical Sciences, symbols, CIRCULAR-VELOCITY CURVE, Halo, astro-ph.SR, Hertzsprung–Russell diagram, stars: luminosity function, astro-ph.GA, Posterior probability, Population, main-sequence, Luminosity-Function, FOS: Physical sciences, Mass-Function, Astronomy & Astrophysics, Computer Science::Digital Libraries, Photometry (optics), DWARF LUMINOSITY-FUNCTION, dwarf luminosity-function, sky-survey, symbols.namesake, Settore FIS/05 - Astronomia e Astrofisica, luminosity function [stars], low-mass [Stars], 0103 physical sciences, Stars: luminosity: mass function, Stars: low-mass, WHITE-DWARFS, education, Solar and Stellar Astrophysics (astro-ph.SR), brown dwarf, catalogs, astrometry, Hertzsprung-Russell and C-M diagrams, stars: low-mass, solar neighborhood, Astrophysics - Astrophysics of Galaxies, SKY-SURVEY, white-dwarfs, Science & Technology, 010308 nuclear & particles physics, Luminosity function, White dwarf, TRIGONOMETRIC PARALLAXES, Astronomy and Astrophysics, Low-mass, 115 Astronomy, Space science, WIDE BINARIES, Stars, Physics::History of Physics, 13. Climate action, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), solar-neighborhood, Catalogs, circular-velocity curve, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph]
Abstract: Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use., Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue., Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun., Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
Published: 2021
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33. Cytoreductive surgery and HIPEC in colorectal cancer—did we get hold of the wrong end of the stick?

Author: Can Yurttas, Delia Cortés-Guiral, Haen Sebastian, Markus W. Löffler, Ingmar Königsrainer, Oliver M. Fisher, Alfred Königsrainer, Winston Liauw, and Stefan Beckert
Subjects: medicine.medical_specialty, business.industry, Colorectal cancer, Hematology, 030230 surgery, medicine.disease, law.invention, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, Randomized controlled trial, law, Basic research, 030220 oncology & carcinogenesis, medicine, Cytostatic drugs, Therapeutic failure, Hyperthermic intraperitoneal chemotherapy, Intensive care medicine, business, Cytoreductive surgery
Abstract: SummaryCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a multimodal treatment approach combining surgical interventions of varying extent with administration of heated cytostatic drugs flushed through the abdominal cavity. Hitherto, this treatment has been popular for peritoneal metastasis (PM), e.g. from colorectal cancer (CRC). Recent randomized controlled trials (RCT) question the benefit of HIPEC in its present form for CRC treatment and raise fundamental issues, eliciting discussions and expert statements regarding HIPEC relevance and interpretation of these results. Unfortunately, such discussions have to remain uninformed, due to the lacking publication of crucial peer reviewed RCT results. Novel basic research aware of HIPEC futility suggests there may be systematic limitations. Innovative modelling approaches for HIPEC may shed light on the reasons for therapeutic failure of frequently used drugs and may lead the way to select better alternatives and/or more rational approaches for the design of HIPEC procedures (e.g. regarding exposure time or temperature). Available evidence strongly supports the notion that CRS is the mainstay for the treatment effects observed in PM from CRC. Unfortunately, HIPEC has become a surrogate for surgical expertise in the field and optimal surgery may therefore outweigh the potentially harmful effects of HIPEC treatment, particularly in lieu of modern systemic chemotherapies. The current situation which frequently is assumed to be deadlocked should be regarded as a challenge to investigate HIPEC with well-designed prospective clinical trials, potentially even constituting an opportunity for introducing innovative trial designs that solve the multifaceted issues of a very heterogeneous treatment approach.
Published: 2020
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34. Individualisierte Immuntherapie von Tumorerkrankungen mittels Peptidimpfstoffen – Funktioniert das vielleicht doch?

Author: Hans-Georg Rammensee and Markus W. Löffler
Subjects: Gynecology, 0303 health sciences, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Hla molecules, 030220 oncology & carcinogenesis, Political science, Public Health, Environmental and Occupational Health, medicine, 030304 developmental biology
Abstract: ZusammenfassungBereits der Arzt und Forscher Paul Ehrlich stellte die These auf, dass das Immunsystem nicht nur Infektionen bekämpft, sondern auch gegen Krebs vorgehen kann. Über die möglichen positiven Auswirkungen einer simultanen Infektion auf den Verlauf einer Krebserkrankung wurde bereits im alten Ägypten ca. 2600 v. Chr. berichtet. Jedoch wurde erst ab den 1960er-Jahren klar, dass das Immunsystem Krebszellen gezielt bekämpfen kann, und erst ab den 1990er-Jahren wurde langsam aufgeklärt, wie dies vor sich geht.Vor diesem Hintergrund sollen deshalb die Bemühungen der letzten 30 Jahre hinsichtlich der Entwicklung therapeutischer Impfungen gegen Krebserkrankungen kurz zusammengefasst und deren bisherige Erfolglosigkeit beleuchtet werden. Außerdem werden in einem Ausblick zukünftige eventuell Erfolg versprechende Entwicklungen in diesem Kontext diskutiert. Dabei werden die verfügbare wissenschaftliche Literatur, aber auch eigene Ergebnisse berücksichtigt.Es ergeben sich ganz zentrale Fragen, etwa: Wie unterscheiden sich Krebszellen von normalen Zellen? Wie kann das Immunsystem diese Unterschiede erkennen? Was sind tumorspezifische Antigene? Warum müssen tumorspezifische Antigene in individueller Weise ausgesucht und angewendet werden? Wie induziert man eine effiziente Immunantwort? Welche pharmazeutischen Formulierungen, Adjuvanzien und Impfrouten sind effektiv?Letztlich stellen wir dar, warum es sich möglicherweise doch lohnt, die bisher völlig erfolglose Peptidimpfung (gemessen an bisher zugelassenen Therapeutika) weiterzuverfolgen.
Published: 2020
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35. Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire

Author: Hans-Georg Rammensee, Peter Brossart, Markus W. Löffler, and Sebastian P. Haen
Subjects: 0301 basic medicine, New horizons, medicine.medical_treatment, T-Lymphocytes, Antigen presentation, Cancer immunotherapy, Computational biology, Review Article, 03 medical and health sciences, 0302 clinical medicine, Antigen, Immunoediting, Antigens, Neoplasm, HLA Antigens, Neoplasms, medicine, Humans, Exome, Immune Checkpoint Inhibitors, Antigen Presentation, business.industry, Repertoire, Immunotherapy, Evidence-based medicine, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Tumour vaccines, Tumour immunology, Identification (biology), business
Abstract: Immune-checkpoint inhibition provides an unmatched level of durable clinical efficacy in various malignancies. Such therapies promote the activation of antigen-specific T cells, although the precise targets of these T cells remain unknown. Exploiting these targets holds great potential to amplify responses to treatment, such as by combining immune-checkpoint inhibition with therapeutic vaccination or other antigen-directed treatments. In this scenario, the pivotal hurdle remains the definition of valid HLA-restricted tumour antigens, which requires several levels of evidence before targets can be established with sufficient confidence. Suitable antigens might include tumour-specific antigens with alternative or wild-type sequences, tumour-associated antigens and cryptic antigens that exceed exome boundaries. Comprehensive antigen classification is required to enable future clinical development and the definition of innovative treatment strategies. Furthermore, clinical development remains challenging with regard to drug manufacturing and regulation, as well as treatment feasibility. Despite these challenges, treatments based on diligently curated antigens combined with a suitable therapeutic platform have the potential to enable optimal antitumour efficacy in patients, either as monotherapies or in combination with other established immunotherapies. In this Review, we summarize the current state-of-the-art approaches for the identification of candidate tumour antigens and provide a structured terminology based on their underlying characteristics., Immune-checkpoint inhibition has transformed the treatment of patients with advanced-stage cancers. Nonetheless, the specific antigens targeted by T cells that are activated or reactivated by these agents remain largely unknown. In this Review, the authors describe the characterization and classification of tumour antigens including descriptions of the most appropriate detection methods, and discuss potential regulatory issues regarding the use of tumour antigen-based therapeutics., Key points Immune-checkpoint inhibition has profoundly changed the paradigm for the care of several malignancies. Although these therapies activate antigen-specific T cells, the precise mechanisms of action and their specific targets remain largely unknown.Anticancer immunotherapies encompass two fundamentally different therapeutic principles based on knowledge of their therapeutic targets, that either have been characterized (antigen-aware) or have remained elusive (antigen-unaware).HLA-presented tumour antigens of potential therapeutic relevance can comprise alternative or wild-type amino acid sequences and can be subdivided into different categories based on their mechanisms of formation.The available methods for the detection of HLA-presented antigens come with intrinsic challenges and limitations and, therefore, warrant multiple lines of evidence of robust tumour specificity before being considered for clinical use.Knowledge obtained using various antigen-detection strategies can be combined with different therapeutic platforms to create individualized therapies that hold great promise, including when combined with already established immunotherapies.Tailoring immunotherapies while taking into account the substantial heterogeneity of malignancies as well as that of HLA loci not only requires innovative science, but also demands innovative approaches to trial design and drug regulation.
Published: 2020

36. Tumorvakzinierung – therapeutische Vakzinierung gegen Krebs

Author: Cécile Gouttefangeas, Hans-Georg Rammensee, Juliane S. Walz, Markus W. Löffler, C. Bokemeyer, and S. P. Haen
Subjects: Gynecology, 0303 health sciences, medicine.medical_specialty, business.industry, Cancer, Hepatology, Tumor vaccines, medicine.disease, Vaccination, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Internal Medicine, medicine, Antigens neoplasm, business, 030304 developmental biology
Abstract: ZusammenfassungTumorzellen weisen immer Veränderungen im Vergleich zu normalen Zellen auf. Die Veränderungen können vom Immunsystem erkannt werden, was zur Zerstörung der Tumorzellen durch T‑Zellen führen kann. Der Erfolg der Immuncheckpointinhibition beispielsweise beim malignen Melanom hat dies eindrucksvoll gezeigt. Viele Tumorerkrankungen sprechen jedoch nicht auf eine solche Therapie an. Hier könnte eine Vakzinierung gegen Tumorantigene hilfreich sein. Allerdings waren alle Bestrebungen in den letzten 30 Jahren praktisch erfolglos. Mit den heutigen Kenntnissen besteht jedoch neue Hoffnung.
Published: 2020
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37. Orf Virus-Based Vectors Preferentially Target Professional Antigen-Presenting Cells, Activate the STING Pathway and Induce Strong Antigen-Specific T Cell Responses

Author: Melanie, Müller, Alena, Reguzova, Markus W, Löffler, and Ralf, Amann
Subjects: T-Lymphocytes, Leukocytes, Mononuclear, Antigen-Presenting Cells, Humans, Membrane Proteins, Orf virus, Transgenes
Abstract: Orf virus (ORFV)-based vectors are attractive for vaccine development as they enable the induction of potent immune responses against specific transgenes. Nevertheless, the precise mechanisms of immune activation remain unknown. This study therefore aimed to characterize underlying mechanisms in human immune cells.Peripheral blood mononuclear cells were infected with attenuated ORFV strain D1701-VrV and analyzed for ORFV infection and activation markers. ORFV entry in susceptible cells was examined using established pharmacological inhibitors. Using the THP1-Dual™ reporter cell line, activation of nuclear factor-κB and interferon regulatory factor pathways were simultaneously evaluated. Infection with an ORFV recombinant encoding immunogenic peptides (PepTrio-ORFV) was used to assess the induction of antigen-specific CD8+ T cells.ORFV was found to preferentially target professional antigen-presenting cells (APCs)Our findings confirm that ORFV induces a strong antigen-specific immune response dependent on APC uptake and activation. These data support the notion that ORFV D1701-VrV is a promising vector for vaccine development and the design of innovative immunotherapeutic applications.
Published: 2022

38. Quantum detector tomography applied to the human visual system: a feasibility study

Author: T. H. A. van der Reep, D. Molenaar, W. Löffler, and Y. Pinto
Subjects: FOS: Computer and information sciences, Quantum Physics, Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, FOS: Physical sciences, Neurons and Cognition (q-bio.NC), Applications (stat.AP), Computer Vision and Pattern Recognition, Quantum Physics (quant-ph), Statistics - Applications, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials
Abstract: We show that quantum detector tomography can be applied to the human visual system to explore human perception of photon number states. In detector tomography, instead of using very hard to produce photon number states, the response of a detector to light pulses with known photon statistics of varying intensity is recorded, and a model is fitted to the experimental outcomes thereby inferring the detector's photon number state response. Generally, light pulses containing a Poisson-distributed number of photons are utilised, which are very easy to produce in the lab. This technique has not been explored to study the human visual system before, because it usually requires a very large number of repetitions not suitable for experiments on humans. Yet, in the present study we show that detector tomography is feasible for human experiments. Assuming a simple model for this accuracy, the results of our simulations show that detector tomography is able to reconstruct the model using Bayesian inference with as little as $5000$ trials. We then optimize the experimental parameters in order to maximise the probability of showing that the single-photon accuracy is above chance. As such, our study opens the road to study human perception on quantum level., Comment: 22 pages, 15 figures (excluding subfigures). Accepted version
Published: 2022
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39. A survey among physicians in surgery and anesthesiology departments after the first surge of SARS-CoV-2 infections in Germany : Preparing for further challenges ahead

Author: Anna Grishina, Fabian Link, Arne Arend, Florentine Kleemann, Pinkus Tober-Lau, Dominik Andree, Friederike Münn, Magdalena Gruendl, Markus Quante, Hans Lederhuber, Markus Albertsmeier, Florian Struller, Robert Grützmann, Alfred Königsrainer, and Markus W. Löffler
Subjects: Work-related dissatisfaction, SARS-CoV-2, Healthcare, Medizin, COVID-19, Working conditions, General Medicine, Cross-Sectional Studies, Anesthesiology, Germany, Physicians, Surveys and Questionnaires, Humans, Original Article, Stress factors
Abstract: Summary Background The SARS-CoV‑2 pandemic has extensively challenged healthcare systems all over the world. Many elective operations were postponed or cancelled, changing priorities and workflows in surgery departments. Aims The primary aim of this cross-sectional study was to assess the workload and psychosocial burden of surgeons and anesthesiologists, working in German hospitals during the first wave of SARS-CoV‑2 infections in 2020. Methods Quantitative online survey on the workplace situation including psychosocial and work-related stress factors among resident and board-certified surgeons and anesthesiologists. Physicians in German hospitals across all levels of healthcare were contacted via departments, professional associations and social media posts. Results Among 154 total study participants, 54% of respondents stated a lack of personal protective equipment in their own wards and 56% reported increased staff shortages since the onset of the pandemic. While routine practice was reported as fully resumed in 71% of surgery departments at the time of the survey, work-related dissatisfaction among responding surgeons and anesthesiologists increased from 24% before the pandemic to 36% after the first wave of infections. As a countermeasure, 94% of participants deemed the establishment of action plans to increase pandemic preparedness and strengthening German public health systems a useful measure to respond to current challenges. Conclusion The aftermath of the first wave of SARS-CoV‑2 infections in Germany has left the surgical staff strained, despite temporarily decreased workloads. Overall, a critical review of the altered conditions is indispensable to identify and promote effective solutions and prudent action plans required to address imminent challenges.
Published: 2022

40. Phase I/II multicenter trial of a novel therapeutic cancer vaccine, HepaVac-101, for hepatocellular carcinoma

Author: Markus W. Löffler, Stefania Gori, Francesco Izzo, Andrea Mayer-Mokler, Paolo A. Ascierto, Alfred Königsrainer, Yuk Ting Ma, Bruno Sangro, Sven Francque, Luisa Vonghia, Alessandro Inno, Antonio Avallone, Jörg Ludwig, Diego Duarte Alcoba, Christian Flohr, Katrin Aslan, Regina Mendrzyk, Heiko Schuster, Marco Borrelli, Danila Valmori, Tanguy Chaumette, Regina Heidenreich, Cécile Gouttefangeas, Greta Forlani, Maria Tagliamonte, Caterina Fusco, Roberta Penta, Mercedes Iñarrairaegui, Ulrike Gnad-Vogt, Carsten Reinhardt, Toni Weinschenk, Roberto S. Accolla, Harpreet Singh-Jasuja, Hans-Georg Rammensee, and Luigi Buonaguro
Subjects: Cancer Research, Tumor-associated antigens, Carcinoma, Hepatocellular, cancer immunotherapy, HLA-A Antigens, Hepatocellular carcinoma, Liver Neoplasms, Cancer Vaccines, Adjuvants, Immunologic, Oncology, Humans, Immunotherapy, Human medicine, Peptides, cancer vaccine
Abstract: Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. Patients and Methods: A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints. Results: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. Conclusions: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I– and class II–restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.
Published: 2022

41. Release of the Pre-Assembled naRNA-LL37 Composite DAMP Re-Defines Neutrophil Extracellular Traps (NETs) as Intentional DAMP Webs

Author: Francesca Bork, Carsten L. Greve, Christine Youn, Sirui Chen, Yu Wang, Masoud Nasri, Jule Focken, Jasmin Scheurer, Pujan Engels, Marissa Dubbelaar, Katharina Hipp, Birgit Schittek, Stefanie Bugl, Markus W. Löffler, Julia Skokowa, Nathan K. Archer, and Alexander N.R. Weber
Subjects: History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Abstract: Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs), the primary human leukocyte population. NETs trap and kill microbes but have also been linked to inflammation, e.g. atherosclerosis, arthritis or psoriasis by unknown mechanisms. We here characterize naRNA (NET-associated RNA), as a new canonical, abundant, and unexplored inflammatory NET component. naRNA, upon release by NET formation, drove further NET formation in naïve PMN, and induced macrophage and keratinocyte activation via TLR8 in humans and Tlr13 in mice, in vitro and in vivo. Importantly, in vivo naRNA strongly drove skin inflammation, whereas genetic ablation of RNA sensing drastically ameliorated psoriatic skin inflammation. Rather than accidentally assembling with LL37 on the NET, naRNA was intracellularly pre-associated in resting neutrophils as a ‘composite DAMP’, thus highlighting NET formation as a DAMP release process. This re-defines sterile NETs as an intentionally inflammatory agent, signaling and amplifying neutrophil activation. Moreover, in the many conditions previously linked to NETs and extracellular RNA, TLR-mediated naRNA sensing emerges as both potential cause and new intervention target.Graphical abstractCreated with biorender.com
Published: 2022
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42. Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study

Author: Christina Fotopoulou, Tabassum Khan, Juraj Bracinik, James Glasbey, Nadeem Abu-Rustum, Luis Chiva, Anna Fagotti, Keiichi Fujiwara, Rahel Ghebre, Murat Gutelkin, Thomas O. Konney, Joseph Ng, Rene Pareja, Rajkumar Kottayasamy Seenivasagam, Jalid Sehouli, Shylasree T.S. Surappa, Aneel Bhangu, Elaine Leung, Sudha Sundar, Dmitri Nepogodiev, Kwabena Siaw-Acheampong, Ruth A. Benson, Edward Bywater, Daoud Chaudhry, Brett E. Dawson, Jonathan P. Evans, James C. Glasbey, Rohan R. Gujjuri, Emily Heritage, Conor S. Jones, Sivesh K. Kamarajah, Chetan Khatri, Rachel A. Khaw, James M. Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S. Mann, Ella J. Marson, Kenneth A. McLean, Siobhan C. Mckay, Emily C. Mills, Gianluca Pellino, Maria Picciochi, Elliott H. Taylor, Abhinav Tiwari, Joana FF. Simoes, Isobel M. Trout, Mary L. Venn, Richard JW. Wilkin, Tom EF. Abbott, Sadi Abukhalaf, Michel Adamina, Adesoji O. Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeier, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P. Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K. Bankhead-Kendall, Emma Barlow, David Beard, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A. Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J. Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F. Cunha, Giana H. Davidson, Anant Desai, Salomone Di Saverio, Thomas M. Drake, John G. Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Gallo, Dhruva Ghosh, Gustavo Mendonça Ataíde Gomes, Gustavo Grecinos, Ewen A. Griffiths, Magdalena Gruendl, Constantine Halkias, Ewen M. Harrison, Intisar Hisham, Peter J. Hutchinson, Shelley Hwang, Arda Isik, Michael D. 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Barrett-Brown, Coonar A, Durio Yates H, Gearon D, Hogan J, King M, Peryt A, Pradeep IS, Adishesh M, Atherton R, Baxter K, Brocklehurst M, Chaudhury M, Krishnamohan N, McAleer J, Owens G, Parkin E, Patkar P, Phang I, Aladeojebi A, Ali M, Barmayehvar B, Gaunt A, Gowda M, Halliday E, Kitchen M, Mansour F, Nanjaiah P, Zakai D, N. Abbassi-Ghadi, Assalaarachchi H, Currie A, Flavin M, Frampton A, Hague M, Hammer C, Hopper J, Horsnell J, Humphries S, Kamocka A, Madhuri TK, Preston S, Singh P, Stebbing J, Tailor A, Walker D, Coomber E, Jaunoo S, Kennedy L, Airey A, Bunni J, Crowley R, Fairhurst K, Frost J, George R, Lee S, Mitchell S, Phull J, Richards S, Aljanadi F, Campbell A, Glass A, Hraishawi I, Jones M, McIlmunn C, McIntosh S, Mhandu P, O’Donnell C, Turkington R, Z. Al-Ishaq, Bhasin S, Bodla AS, Burahee A, Crichton A, A. El-Ghobashy, Fossett R, Pigadas N, Rahman E, Snee D, Vidya R, Yassin N, Fountain D, M.T. Hasan, Karabatsou K, Laurente R, Pathmanaban O, Barlow C, Ding D, Foster J, Longstaff L, C. Brett-Miller, Buruiana FE, Al-mukhtar A, Edwards J, Giblin A, Kelty C, Lee M, Lye G, Newman T, Sharkey A, Steele C, Sureshkumar Shah N, Whitehall E, Blair J, Lakhiani A, W. Parry-Smith, Sahu B, Athwal R, Baker A, Jones L, Konstantinou C, Ramcharan S, Vatish J, Wilkin R, Alzetani A, Amer K, Badran A, Colvin HV, Ethunandan M, Sekhon GK, Shakoor Z, Shields H, Singh R, Talbot T, Wensley F, Lawday S, Lyons A, Newman S, Chung E, Hagger R, Hainsworth A, Hunt I, Karim A, Owen H, Ramwell A, Santhirakumaran G, Smelt J, Tan C, Vaughan P, Williams K, Baker C, Davies A, Gossage J, Kelly M, Knight W, Bromage S, Hall J, Kaushik V, Rudic M, Vallabh N, Zhang Y, Harris G, James G, Kang C, Lin DJ, Rajgor AD, Royle T, Scurrah R, Steel B, Watson LJ, Choi D, Hutchison R, Luoma V, Marcus HJ, May R, Menon A, Pramodana B, Webber L, Hayes A, Jones R, Sivarajah G, Smith M, Smrke A, Strauss D, Abouelela FAM, Aneke IA, Asaad P, Brown B, Collis J, Duff S, Khan A, Moura F, Taylor M, Wadham B, Warburton H, Elmoslemany T, M.D. Jenkinson, Millward CP, Zakaria R, Mccluney S, Parmar C, Shah S, Allison J, M.S. Babar, Bowen J, Collard B, Goodrum S, Lau K, Sargent M, Scott R, Thomas E, Whitmore H, Balasubramaniam D, Jayasankar B, Kapoor S, Ramachandran A, Semple C, Elhamshary A, Imam SMB, Kapriniotis K, Kasivisvanathan V, Lindsay J, S. Rakhshani-Moghadam, Beech N, Chand M, Green L, Kalavrezos N, Kiconco H, McEwen R, Schilling C, Sinha D, Pereca J, Chopra S, Egbeare D, Thomas R, Arumugam S, Ibrahim B, Khan K, Combellack T, Hill G, Jones S, Kornaszewska M, Mohammed M, Tahhan G, Valtzoglou V, Blencowe N, Eskander P, Gash K, Gourbault L, Hanna M, Maccabe TA, Main B, Olivier J, Newton C, Roswadowski S, Ryan N, Teh E, West D, Al-omishy H, Baig M, Bates H, Di Taranto G, Dickson K, Dunne N, Gill C, Howe D, Jeevan D, Khajuria A, A. Martin-Ucar, McEvoy K, Naredla P, Robertson S, Sait M, Sarma DR, Shanbhag S, Shortland T, Simmonds S, Skillman J, Tewari N, Walton G, M.A. Akhtar, Brunt A, McIntyre J, Milne K, Rashid MM, Sgrò A, Stewart KE, Turnbull A, A.K. Abou-Foul, Gossedge G, O’Donnell S, Oldfield F, Thomson S, Aguilar Gonzalez M, Talukder S, Boyle C, Fernando D, Gallagher K, Laird A, Tham D, Bath M, Basnyat P, Davis H, Montauban P, Shrestha A, Agarwal K, Arif T, Magee C, Nambirajan T, Powell S, Vinayagam R, Flindall I, Hanson A, Mahendran V, Green S, Lim M, MacDonald L, Miu V, Onos L, Sheridan K, Young R, Alam F, Griffiths O, Houlden C, Kolli VS, Lala AK, Leeson S, Peevor R, Seymour Z, Consorti E, Gonzalez R, Grolman R, R. Kwan-Feinberg, Liu T, Merzlikin O, San Francisco, Brown A, Cooper Z, Hirji S, Jolissaint J, Mahvi D, Okafor B, Raut CP, Roxo V, Salim A, Bessen S, Chen L, Dagrosa L, Fay K, Fleischer C, Hasson R, Henderson E, Leech M, Loehrer A, Markey C, Paydarfar J, Rosenkranz K, Telma K, Tocci N, I. Wilkinson-Ryan, Bokenkamp M, Brown K, Fleming D, Heron C, Hill C, Kay H, Leede E, McElhinney K, Olson KA, Osterberg EC, Riley C, Srikanth P, Barbour J, Blazer D, DiLalla GA, Fayanju O, Hwang ES, Kahmke R, Kazaure H, Lazarides A, Lee W, Lidsky M, Menendez C, Moris D, Plichta J, Pradhan MC, Puscas L, Rice HE, Rocke D, Rosenberger L, Scheri R, B.D. Smith, M.T. Stang, Tolnitch L, Turnage K, Visgauss J, Walton FS, Watts T, Zani S, Farma J, Cardona K, Russell MC, Clark J, Kwon D, Goel N, Kronenfeld J, Bigelow B, Etchill E, A. Gabre-Kidan, Jenny H, Kent A, Ladd MR, Long C, Malapati H, Margalit A, Rapaport S, Rose J, Stevens K, Tsai L, Vervoort D, Yesantharao P, Dehal A, Klaristenfeld D, Huynh K, Kaafarani H, Naar L, Qadan M, Brown L, Ganly I, Mullinax JE, Alpert N, Gillezeau C, F.A.C.S.B.A. Miles DDS MD, Taioli E, Cha DE, Gleeson E, Horn C, Sarpel U, Gusani N, Hazelton J, Maines J, Oh JS, Ssentongo A, Ssentongo P, Bhama A, Colling K, Najarian M, Azam M, Choudhry A, Marx W, Abedin Y, Arzumanov G, Chokshi R, Gabrilovich S, Glass N, Kalyoussef E, F.P. Parvin-Nejad, Roden D, Stein J, A. Suarez-Ligon, Tsui G, Zhao K, Fleming J, Fuson A, Gigliotti J, Ovaitt A, Ying Y, Abel MK, Andaya V, Bigay K, M.A. Boeck, Chern H, Corvera C, I. El-Sayed, Glencer A, Ha P, B.C.S. Hamilton, Heaton C, Hirose K, D.M. Jablons, Kirkwood KS, Kornblith LZ, Kratz JR, Lee RH, Miller PN, Nakakura EK, B. Nunez-Garcia, O’Donnell RJ, Ozgediz D, Park P, Robinson B, Sarin A, Sheu B, Varma MG, Wai KC, Wustrack R, Xu MJ, Zimel M, CA) Beswick D, Goddard J, Manor J, Song J, Denver/Colorado Springs/Loveland, Cioci A, Pavlis W, Rakoczy K, Ruiz G, Saberi R, Fullmer T, Gaskill C, Gross N, Kiong K, Roland CL, Zafar SN, Abdallah M, Abouassi A, Aigbivbalu E, Almasri M, Eid J, George B, Kulkarni G, Marwan H, Mehdi M, San Andrés M, Sundaresan J, Aoun SG, Ban VS, Batjer HH, Bosler K, Caruso J, Sumer B, Abbott D, Acher A, Aiken T, Barrett J, Foley E, Schwartz PB, Hawkins AT, Maiga A, Ruzgar NM, Sion M, Ullrich S, Laufer J, Scasso S, H. Al-Naggar, M. Al-Shehari, Almassaudi A, Alsayadi M, Alsayadi R, Nahshal M, Shream S, AL-Ameri S, Aldawbali M, Fotopoulou, C, Khan, T, Bracinik, J, Glasbey, J, Abu-Rustum, N, Chiva, L, Fagotti, A, Fujiwara, K, Ghebre, R, Gutelkin, M, Konney, T, Ng, J, Pareja, R, Kottayasamy Seenivasagam, R, Sehouli, J, Surappa, S, Bhangu, A, Leung, E, Sundar, S, Fruscio, R, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genital Neoplasms, Female/epidemiology/surgery, complications, SARS-CoV-2, delay, pandemic, Obstetrics and Gynecology, COVID-19, [SDV.CAN]Life Sciences [q-bio]/Cancer, complication, General Medicine, Covid-19, surgery, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Humans, Female, gynecologic cancer, Prospective Studies, complicationsCOVID-19delaygynecologic cancerpandemicsurgery, Pandemics
Abstract: Background: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear. Objective: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes. Study design: This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19- related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death. Results: We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355 ; 15.7% ; P
Published: 2022
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43. A comprehensive quality control workflow for paired tumor-normal NGS experiments.

Author: Christopher M. Schroeder, Franz J. Hilke, Markus W. Löffler, Michael Bitzer, Florian Lenz, and Marc Sturm
Published: 2017
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44. Prolonged Exposure to Oxaliplatin during HIPEC Improves Effectiveness in a Preclinical Micrometastasis Model

Author: Nick, Seyfried, Can, Yurttas, Markus, Burkard, Benedikt, Oswald, Alexander, Tolios, Franziska, Herster, Joseph, Kauer, Tarkan, Jäger, Ingmar, Königsrainer, Karolin, Thiel, Markus, Quante, Hans-Georg, Rammensee, Sascha, Venturelli, Matthias, Schwab, Alfred, Königsrainer, Stefan, Beckert, and Markus W, Löffler
Abstract: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients' samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.
Published: 2021

45. Integrin activation enables rapid detection of functional Vδ1

Author: Nicola, Herold, Anna, Schöllhorn, Adrian, Feile, Andrea, Gaißler, Anne, Mohrholz, Graham, Pawelec, Markus W, Löffler, Stoyan, Dimitrov, Cécile, Gouttefangeas, and Kilian, Wistuba-Hamprecht
Subjects: Integrins, T-Lymphocyte Subsets, Cytokines, Receptors, Antigen, T-Cell, gamma-delta, CD8-Positive T-Lymphocytes, Lymphocyte Activation
Abstract: Conformational change of the β2 integrin lymphocyte function-associated antigen 1 (LFA-1) is an early marker of T cell activation. A protocol using the mAb clone m24 recognizing the active, extended high-affinity conformation has been previously described for the assessment of functional CD4
Published: 2021

46. Can Any Drug Be Repurposed for Cancer Treatment? A Systematic Assessment of the Scientific Literature

Author: Nicolai Stransky, Peter Ruth, Matthias Schwab, and Markus W. Löffler
Subjects: repositioning, Perspective, systematic assessment, repurposing, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cancer, meta research, RC254-282
Abstract: Simple Summary Drug repurposing strategies utilize drugs, already approved by regulatory authorities, to test their efficacy against different diseases. While this approach is increasingly used, according to the literature, there are few systematic assessments of these efforts so far. In this work, we tried to answer the question: How many approved drugs show anti-cancer effects according to the literature? We found that the majority (69%) of the approved drugs we analyzed did show anti-cancer effects in preclinical studies. The assessment of the methodological quality of the reports, namely, the reporting quality and usage of bias-reducing methods, showed that the methodological quality of the articles was by and large moderate, while many items of the quality assessment were lacking in most reports (for example, blinding, preregistration, power calculations, and detailed information on lab animals). We hypothesize that the current reward systems favor positive results over high methodological quality, probably leading to many false-positive results. Abstract Drug repurposing is a complementary pathway for introducing new drugs against cancer. Broad systematic assessments of ongoing repurposing efforts in oncology are lacking, but may be helpful to critically appraise current and future efforts. Hence, we conducted a systematic PubMed search encompassing 100 frequently prescribed and 100 randomly selected drugs, and assessed the published preclinical anti-cancer effects. Furthermore, we evaluated all the identified original articles for methodological quality. We found reports indicating anti-cancer effects for 138/200 drugs, especially among frequently prescribed drugs (81/100). Most were reports suggesting single-agent activity of the drugs (61%). Basic information, such as the cell line used or control treatments utilized, were reported consistently, while more detailed information (e.g., excluded data) was mostly missing. The majority (56%) of in vivo studies reported randomizing animals, while only few articles stated that the experiments were conducted in a blinded fashion. In conclusion, we found promising reports of anti-cancer effects for the majority of the assessed drugs, but speculate that many of them are false-positive findings. Reward systems should be adjusted to encourage the widespread usage of high reporting quality and bias-reducing methodologies, aiming to decrease the rate of false-positive results, and thereby increasing the trust in the findings.
Published: 2021

47. Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy

Author: Thomas K Eigentler, Teresa Amaral, Benjamin Weide, Graham Pawelec, Tobias Sinnberg, Claus Garbe, Lukas Flatz, Friedegund Meier, Kilian Wistuba-Hamprecht, Alfred Königsrainer, Oltin T Pop, Jonas Bochem, Henning Zelba, Janine Spreuer, Andrea Gaissler, Karolin Thiel, Can Yurttas, Daniel Soffel, Stephan Forchhammer, Heike Niessner, and Markus W Löffler
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2021

48. Elective cancer surgery in COVID-19–Free surgical pathways during the SARS-cov-2 pandemic: An international, multicenter, comparative cohort study

Author: James C Glasbey, Dmitri Nepogodiev, Joana Ff Simoes, Omar Omar, Elizabeth Li, Mary L Venn, Mohammad Abou Chaar, Vita Capizzi, Daoud Chaudhry, Anant Desai, Jonathan G Edwards, Jonathan P Evans, Marco Fiore, Jose Flavio Videria, Samuel J Ford, Ian Ganyli, Ewen A Griffiths, Rohan R Gujjuri, Angelos G Kolias, Haytham Ma Kaafarani, Ana Minaya-Bravo, Siobhan C McKay, Helen M Mohan, Keith Roberts, Carlos San Miguel-Méndez, Peter Pockney, Richard Shaw, Neil J Smart, Grant D Stewart, Sudha Sundar, Raghavan Vidya, Aneel A Bhangu, James C Glasbey, Omar Omar, Aneel A Bhangu, Kwabena Siaw-Acheampong, Ruth A Benson, Edward Bywater, Daoud Chaudhry, Brett E Dawson, Jonathan P Evans, James C Glasbey, Rohan R Gujjuri, Emily Heritage, Conor S Jones, Sivesh K Kamarajah, Chetan Khatri, Rachel A Khaw, James M Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S Mann, Ella J Marson, Kenneth A McLean, Siobhan C McKay, Emily C Mills, Dmitri Nepogodiev, Gianluca Pellino, Maria Picciochi, Elliott H Taylor, Abhinav Tiwari, Joana Ff Simoes, Isobel M Trout, Mary L Venn, Richard Jw Wilkin, Aneel A Bhangu, James C Glasbey, Neil J Smart, Ana Minaya-Bravo, Jonathan P Evans, Gaetano Gallo, Susan Moug, Francesco Pata, Peter Pockney, Salomone Di Saverio, Abigail Vallance, Dale Vimalchandran, Ewen A Griffiths, Sivesh K Kamarajah, Richard Pt Evans, Philip Townend, Keith Roberts, Siobhan McKay, John Isaac, Sohei Satoi, John Edwards, Aman S Coonar, Adrian Marchbank, Edward J Caruana, Georgia R Layton, Akshay Patel, Alessandro Brunelli, Samuel Ford, Anant Desai, Alessandro Gronchi, Marco Fiore, Max Almond, Fabio Tirotta, Sinziana Dumitra, Angelos Kolias, Stephen J Price, Daniel M Fountain, Michael D Jenkinson, Peter Hutchinson, Hani J Marcus, Rory J Piper, Laura Lippa, Franco Servadei, Ignatius Esene, Christian Freyschlag, Iuri Neville, Gail Rosseau, Karl Schaller, Andreas K Demetriades, Faith Robertson, Alex Alamri, Richard Shaw, Andrew G Schache, Stuart C Winter, Michael Ho, Paul Nankivell, Juan Rey Biel, Martin Batstone, Ian Ganly, Raghavan Vidya, Alex Wilkins, Jagdeep K Singh, Dinesh Thekinkattil, Sudha Sundar, Christina Fotopoulou, Elaine Leung, Tabassum Khan, Luis Chiva, Jalid Sehouli, Anna Fagotti, Paul Cohen, Murat Gutelkin, Rahel Ghebre, Thomas Konney, Rene Pareja, Rob Bristow, Sean Dowdy, T S Shylasree, R Kottayasamy Seenivasagam, Joe Ng, Keiiji Fujiwara, Grant D Stewart, Benjamin Lamb, Krishna Narahari, Alan McNeill, Alexandra Colquhoun, John McGrath, Steve Bromage, Ravi Barod, Veeru Kasivisvanathan, Tobias Klatte, Joana Ff Simoes, Tom Ef Abbott, Sadi Abukhalaf, Michel Adamina, Adesoji O Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeiers, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K Bankhead-Kendall, Emma Barlow, David Beard, Ruth A Benson, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F Cunha, Giana H Davidson, Anant Desai, Salomone Di Saverio, Thomas M Drake, John G Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Gallo, Dhruv Ghosh, Gustavo Mendonça Ataíde Gomes, Gustavo Grecinos, Ewen A Griffiths, Madalegna GrÜndl, Constantine Halkias, Ewen M Harrison, Intisar Hisham, Peter J Hutchinson, Shelley Hwang, Arda Isik, Michael D Jenkinson, Pascal Jonker, Haytham Ma Kaafarani, Debby Keller, Angelos Kolias, Schelto Kruijff, Ismail Lawani, Hans Lederhuber, Sezai Leventoglu, Andrey Litvin, Andrew Loehrer, Markus W Löffler, Maria Aguilera Lorena, Maria Marta Modolo, Piotr Major, Janet Martin, Hassan N Mashbari, Dennis Mazingi, Symeon Metallidis, Ana Minaya-Bravo, Helen M Mohan, Rachel Moore, David Moszkowicz, Susan Moug, Joshua S Ng-Kamstra, Mayaba Maimbo, Ionut Negoi, Milagros Niquen, Faustin Ntirenganya, Maricarmen Olivos, Kacimi Oussama, Oumaima Outani, Marie Dione Parreno-Sacdalanm, Francesco Pata, Carlos Jose Perez Rivera, Thomas D Pinkney, Willemijn van der Plas, Peter Pockney, Ahmad Qureshi, Dejan Radenkovic, Antonio Ramos-De la Medina, Keith Roberts, April C Roslani, Martin Rutegård, Juan José Segura-Sampedro, Irène Santos, Sohei Satoi, Raza Sayyed, Andrew Schache, Andreas A Schnitzbauer, Justina O Seyi-Olajide, Neil Sharma, Richard Shaw, Sebastian Shu, Kjetil Soreide, Antonino Spinelli, Grant D Stewart, Malin Sund, Sudha Sundar, Stephen Tabiri, Philip Townend, Georgios Tsoulfas, Gabrielle H van Ramshorst, Raghavan Vidya, Dale Vimalachandran, Oliver J Warren, Duane Wedderburn, Naomi Wright, C Allemand, L Boccalatte, M Figari, M Lamm, J Larrañaga, C Marchitelli, F Noll, D Odetto, M Perrotta, J Saadi, L Zamora, C Alurralde, E L Caram, D Eskinazi, J P Mendoza, M Usandivaras, R Badra, A Esteban, J S García, P M García, J I Gerchunoff, S M Lucchini, M A NIgra, L Vargas, T Hovhannisyan, A Stepanyan, T Gould, R Gourlay, B Griffiths, S Gananadha, M McLaren, J Cecire, N Joshi, S Salindera, A Sutherland, J H Ahn, G Charlton, S Chen, N Gauri, R Hayhurst, S Jang, F Jia, C Mulligan, W Yang, G Ye, H Zhang, M Ballal, D Gibson, D Hayne, J Moss, T Richards, P Viswambaram, U G Vo, J Bennetts, T Bright, M Brooke-Smith, R Fong, B Gricks, Y H Lam, B S Ong, M Szpytma, D Watson, K Bagraith, S Caird, E Chan, C Dawson, D Ho, E Jeyarajan, S Jordan, A Lim, G J Nolan, A Oar, D Parker, H Puhalla, A Quennell, L Rutherford, P Townend, M Von Papen, M Wullschleger, A Blatt, D Cope, N Egoroff, M Fenton, J Gani, N Lott, P Pockney, N Shugg, M Elliott, D Phung, D Phan, D Townend, C Bong, J Gundara, A Frankel, S Bowman, G R Guerra, J Bolt, K Buddingh, N N Dudi-Venkata, S Jog, H M Kroon, T Sammour, R Smith, C Stranz, M Batstone, K Lah, W McGahan, D Mitchell, A Morton, A Pearce, M Roberts, G Sheahan, B Swinson, N Alam, S Banting, L Chong, P Choong, S Clatworthy, D Foley, A Fox, M W Hii, B Knowles, J Mack, M Read, A Rowcroft, S Ward, G Wright, M Lanner, I Königsrainer, M Bauer, C Freyschlag, M Kafka, F Messner, D Öfner, I Tsibulak, K Emmanuel, M Grechenig, R Gruber, M Harald, L Öhlberger, J Presl, A Wimmer, I Namazov, E Samadov, D Barker, R Boyce, S Corbin, A Doyle, A Eastmond, R Gill, A Haynes, S Millar, M O'Shea, G Padmore, N Paquette, E Phillips, S St John, K Walkes, N Flamey, P Pattyn, W Oosterlinck, J Van den Eynde, R Van den Eynde, A Gatti, C Nardi, R Oliva, R De Cicco, I Cecconello, P Gregorio, L Pontual Lima, U Ribeiro Junior, F Takeda, R M Terra, M Sokolov, B Kidane, S Srinathan, M Boutros, N Caminsky, G Ghitulescu, G Jamjoum, J Moon, J Pelletier, T Vanounou, S Wong, M Boutros, S Dumitra, A Kouyoumdjian, B Johnston, C Russell, M Boutros, S Demyttenaere, R Garfinkle, J Abou-Khalil, C Nessim, J Stevenson, F Heredia, A Almeciga, A Fletcher, A Merchan, L O Puentes, J Mendoza Quevedo, G Bacic, D Karlovic, D Krsul, M Zelic, I Luksic, M Mamic, B Bakmaz, I Coza, E Dijan, Z Katusic, J Mihanovic, I Rakvin, K Frantzeskou, N Gouvas, G Kokkinos, P Papatheodorou, I Pozotou, O Stavrinidou, A Yiallourou, L Martinek, M Skrovina, I Szubota, J Žatecký, V Javurkova, J Klat, T Avlund, P Christensen, J L Harbjerg, L H Iversen, D W Kjaer, Hø Kristensen, M Mekhael, A L Ebbehøj, P Krarup, N Schlesinger, H Smith, A Abdelsamed, A Y Azzam, H Salem, A Seleim, A Abdelmajeed, M Abdou, N E Abosamak, M Al Sayed, F Ashoush, R Atta, E Elazzazy, M Elhoseiny, M Elnemr, M S Elqasabi, M E Elsayed Hewalla, I Elsherbini, E Essam, M Eweda, I Ghallab, E Hassan, M Ibrahim, M Metwalli, M Mourad, M S Qatora, M Ragab, A Sabry, H Saifeldin, M Saleh Mesbah Mohamed Elkaffas, A Samih, A Samir Abdelaal, S Shehata, K Shenit, D Attia, N Kamal, N Osman, A M Abbas, Has Abd Elazeem, M M Abdelkarem, S Alaa, A K Ali, A Ayman, M G Azizeldine, H Elkhayat, S M Elghazaly, F A Monib, M A Nageh, M M Saad, M Salah, M Shahine, E A Yousof, A Youssef, A Eldaly, M ElFiky, A Nabil, G Amira, I Sallam, M Sherief, A Sherif, A Abdelrahman, H Aboulkassem, G Ghaly, R Hamdy, A Morsi, H Salem, G Sherif, H Abdeldayem, I Abdelkader Salama, M Balabel, Y Fayed, A E Sherif, D Bekele, J Kauppila, E Sarjanoja, O Helminen, H Huhta, J H Kauppila, C Beyrne, L Jouffret, L Lugans, L Marie-Macron, E Chouillard, B De Simone, J Bettoni, S Dakpé, B Devauchelle, N Lavagen, S Testelin, S Boucher, R Breheret, A Gueutier, A Kahn, J KÜn-Darbois, A Barrabe, Z Lakkis, A Louvrier, S Manfredelli, P Mathieu, A Chebaro, V Drubay, M El Amrani, C Eveno, K Lecolle, G Legault, L Martin, G Piessen, F R Pruvot, S Truant, P Zerbib, Q Ballouhey, B Barrat, J Laloze, H Salle, A Taibi, J Usseglio, D Bergeat, A Merdrignac, Roy B Le, L O Perotto, A Scalabre, A Aimé, A Ezanno, B Malgras, P Bouche, S Tzedakis, E Cotte, O Glehen, V Kepenekian, J Lifante, G Passot, A D'Urso, E Felli, D Mutter, P Pessaux, B Seeliger, J Bardet, R Berry, G Boddaert, S Bonnet, E Brian, C Denet, D Fuks, D Gossot, M Grigoroiu, A Laforest, Y Levy-Zauberman, C Louis-Sylvestre, A Moumen, G Pourcher, A Seguin-Givelet, E Tribillon, E Duchalais, F Espitalier, C Ferron, O Malard, U Bork, M Distler, J Fritzmann, J Kirchberg, C Praetorius, C Riediger, J Weitz, T Welsch, P Wimberger, K Beyer, C Kamphues, J Lauscher, F N Loch, C Schineis, M Albertsmeier, M Angele, A Kappenberger, H Niess, T Schiergens, J Werner, R Becker, J Jonescheit, I Pergolini, D Reim, C Boeker, I Hakami, J Mall, P Liokatis, W Smolka, K Nowak, T Reinhard, F Hölzle, A Modabber, P Winnand, M Knitschke, P Kauffmann, S Wolfer, J Kleeff, K Lorenz, C Michalski, U Ronellenfitsch, R Schneider, E Bertolani, A Königsrainer, M W Löffler, M Quante, C Steidle, L ÜberrÜck, C Yurttas, C S Betz, J Bewarder, A Böttcher, S Burg, C Busch, M Gosau, A Heuer, J Izbicki, T O Klatte, D Koenig, N Moeckelmann, C Nitschke, M Priemel, R Smeets, U Speth, S Thole, F G Uzunoglu, T Vollkommer, N Zeller, M J Battista, K Gillen, A Hasenburg, S Krajnak, V Linz, R Schwab, K Angelou, D Haidopoulos, A Rodolakis, P Antonakis, K Bramis, L Chardalias, I Contis, N Dafnios, D Dellaportas, G Fragulidis, A Gklavas, M Konstadoulakis, N Memos, I Papaconstantinou, A Polydorou, T Theodosopoulos, A Vezakis, M I Antonopoulou, D K Manatakis, N Tasis, N Arkadopoulos, N Danias, P Economopoulou, P Kokoropoulos, A Larentzakis, N Michalopoulos, J Selmani, T Sidiropoulos, V Tsaousis, P Vassiliu, K Bouchagier, S Klimopoulos, D Paspaliari, G Stylianidis, K Baxevanidou, K Bouliaris, P Chatzikomnitsa, M Efthimiou, A Giaglaras, C Kalfountzos, G Koukoulis, A M Ntziovara, K Petropoulos, K Soulikia, I Tsiamalou, K Zervas, S Zourntou, I Baloyiannis, A Diamantis, E Gkrinia, J Hajiioannou, C Korais, O Koukoura, K Perivoliotis, A Saratziotis, C Skoulakis, D Symeonidis, K Tepetes, G Tzovaras, D Zacharoulis, V Alexoudi, K Antoniades, I Astreidis, P Christidis, D Deligiannidis, T Grivas, O Ioannidis, I Kalaitsidou, L Loutzidou, A Mantevas, D Michailidou, K Paraskevopoulos, S Politis, A Stavroglou, D Tatsis, I Tilaveridis, K Vahtsevanos, G Venetis, I Karaitianos, T Tsirlis, A Charalabopoulos, T Liakakos, E Mpaili, D Schizas, E Spartalis, A Syllaios, C Zografos, C Anthoulakis, C Christou, V Papadopoulos, A Tooulias, D Tsolakidis, G Tsoulfas, D Zouzoulas, E Athanasakis, E Chrysos, J Tsiaoussis, S Xenaki, E Xynos, K Futaba, M F Ho, S F Hon, Twc Mak, Ssm Ng, C C Foo, B Banky, N Suszták, M Aremu, A Canas-Martinez, O Cullivan, C Murphy, P Owens, L Pickett, L Akmenkalne, J Byrne, M Corrigan, C Cullinane, A Daly, C Fleming, P Jordan, S Killeen, N Lynch, A McCarthy, H Mustafa, S O'Brien, P O'Leary, Was Syed, L Vernon, D Callanan, L Huang, A Ionescu, P Sheahan, I Balasubramanian, M Boland, K Conlon, D Evoy, N Fearon, T Gallagher, J Geraghty, H Heneghan, N Kennedy, D Maguire, D McCartan, E W McDermott, R S Prichard, D Winter, D Alazawi, C Barry, T Boyle, W Butt, E M Connolly, N Donlon, C Donohue, B A Fahey, R Farrell, C Fitzgerald, J Kinsella, J O Larkin, P Lennon, P 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Cossu, P Cottu, A Fancellu, C F Feo, G C Ginesu, G Giuliani, M Madonia, T Perra, A Piras, A Porcu, D Rizzo, A M Scanu, A Tedde, M Tedde, P Delrio, D Rega, G Badalamenti, G Campisi, A Cordova, M Franza, G Maniaci, G Rinaldi, F Toia, M Calabrò, F Farnesi, E G Lunghi, A Muratore, N S Pipitone Federico, F Bàmbina, G D'Andrea, P Familiari, V Picotti, G De Palma, G Luglio, G Pagano, F P Tropeano, L Baldari, G A Beltramini, L Boni, E Cassinotti, A Gianni, L Pignataro, S Torretta, C Abatini, M Baia, D Biasoni, G Bogani, P Cadenelli, V Capizzi, Spb Cioffi, D Citterio, L V Comini, M Cosimelli, M Fiore, S Folli, M Gennaro, L Giannini, A Gronchi, M Guaglio, A Macchi, F Martinelli, V Mazzaferro, A Mosca, S Pasquali, C Piazza, F Raspagliesi, L Rolli, R Salvioni, G Sarpietro, C Sarre, L Sorrentino, A Agnes, S Alfieri, F Belia, A Biondi, V Cozza, A D'Amore, D D'Ugo, V De Simone, A Fagotti, G Gasparini, L Gordini, F Litta, C P Lombardi, L Lorenzon, A A Marra, F Marzi, A Moro, A Parello, E Perrone, R Persiani, C Ratto, F Rosa, G Saponaro, G Scambia, O Scrima, G Sganga, R Tudisco, A Belli, V Granata, F Izzo, R Palaia, R Patrone, F M Carrano, M M Carvello, A De Virgilio, F Di Candido, F Ferreli, F Gaino, G Mercante, V Rossi, A Spinelli, G Spriano, D M Donati, T Frisoni, E Palmerini, A Aprile, F Barra, P Batistotti, S Ferrero, P Fregatti, S Scabini, M Sparavigna, E Asti, D Bernardi, L Bonavina, A Lovece, L Adamoli, M Ansarin, S Cenciarelli, F Chu, R De Berardinis, U Fumagalli Romario, F Mastrilli, G Pietrobon, M Tagliabue, E Badellino, A Ferrero, R Massobrio, A De Manzoni Garberini, P Federico, P Maida, E Marra, G Marte, A Petrillo, T Tammaro, A Tufo, M Berselli, G Borroni, E Cocozza, L Conti, M Desio, L Livraghi, V Quintodei, A Rizzi, A Zullo, C Baldi, C Corbellini, G M Sampietro, P Cellerino, E Baldini, P Capelli, L Conti, S M Isolani, M Ribolla, A Bondurri, F Colombo, L Ferrario, C Guerci, A Maffioli, T Armao, M Ballabio, P Bisagni, A Gagliano, M Longhi, M Madonini, P PizziCni, A M 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Gupta, J Steinke, S Thrumurthy, E Massie, K McGivern, D Rutherford, M Wilson, J Hardie, S Kazzaz, S Handa, M Kaushal, A Kler, P Patel, J Redfern, S Tezas, Y Aawsaj, S Amonkar, C Barry, L Blackwell, D Blake, J Carter, H Emerson, A Fisher, M Katory, P Korompelis, W McCormick, A Mustafa, L Pearce, N Ratnavelu, R Reehal, L Kretzmer, L Lalou, B Manku, I Parwaiz, J Stafford, M Abdelkarim, A Asqalan, T Gala, S Ibrahim, A Maw, R Mithany, R Morgan, G Sundaram Venkatesan, K Ang, E J Caruana, M F Chowdhry, A Mohammad, A Nakas, S Rathinam, M Boal, O Brown, S Dwerryhouse, S Higgs, A Vallance, E Boyd, V Irvine, A Kirk, G Bakolas, A Boulton, A Chandock, T Khan, M Kumar, P Agoston, A Bille, B Challacombe, S Fraser, K Harrison-Phipps, J King, G Mehra, L Mills, M Najdy, R Nath, L Okiror, J Pilling, V Rizzo, T Routledge, A Sayasneh, L Stroman, A Wali, M Fehervari, C Fotopoulou, N Habib, S Hamrang-Yousefi, Z Jawad, L Jiao, M Pai, J Ploski, P Rajagopal, S Saso, M Sodergren, D Spalding, S Laws, C Hardie, C McNaught, R Alam, A Budacan, J Cahill, M Kalkat, S Karandikar, L Kenyon, D Naumann, A Patel, J Ayorinde, T Chase, T Cuming, A Ghanbari, L Humphreys, S Tayeh, A Aboelkassem Ibrahim, R Bichoo, H Cao, Akw Chai, J Choudhury, C Evans, H Fitzjohn, H Ikram, M Langstroth, M Loubani, A McMillan, S Nazir, Ssa Qadri, A Robinson, E Ross, T Sehgal, A Wilkins, J Dixon, J Dunning, K Freystaetter, M Jha, S Lester, A Madhavan, S V Thulasiraman, Y Viswanath, T Curl-Roper, C Delimpalta, Ccl Liao, V Velchuru, E Westwood, E Belcher, G Bond-Smith, S Chidambaram, F Di Chiara, K Fasanmade, L Fraser, H Fu, M Ganau, S Gore, J Graystone, D Jeyaretna, H Khatkar, M Lami, M Maher, S Mastoridis, R Mihai, R Piper, S Prabhu, Obf Risk, U Selbong, K Shah, R Smillie, H Soleymani Majd, S Sravanam, D Stavroulias, G D Tebala, M Vatish, C Verberne, K Wallwork, S Winter, M I Bhatti, H Boyd-Carson, E Elsey, E Gemmill, P Herrod, M Jibreel, E Lenzi, T Saafan, D Sapre, T Sian, N Watson, A Athanasiou, G Bourke, L Bradshaw, A Brunelli, J Burke, P Coe, F Costigan, H Elkadi, M Ho, J Johnstone, A Kanatas, V Kantola, A Kaufmann, A Laios, S Lam, E MacInnes, S Munot, C Nahm, M Otify, C Pompili, I Smith, G Theophilou, G Toogood, R Wade, D Ward, C West, S Annamalai, C Ashmore, A Boddy, T Hossain, A Kourdouli, A Gvaramadze, A Jibril, L Prusty, D Thekkinkattil, A Harky, M Shackcloth, A Askari, C Chan, N Cirocchi, S Kudchadkar, K Patel, J Sagar, S Shaw, R Talwar, M Abdalla, R Edmondson, O Ismail, D Jones, K Newton, N Stylianides, A Aderombi, U Andaleeb, O Bajomo, K Beatson, W Garrett, M Mehmood, V Ng, R Al-Habsi, G S Divya, B Keeler, B Al-Sarireh, R Egan, R Harries, A Henry, M Kittur, Z Li, K Parkins, F Soliman, N Spencer, D Thompson, C Burgess, C Gemmell, C Grieco, M Hollyman, L Hunt, J Morrison, S Ojha, N Ryan, F Abbadessa, S Barnard, C Chan, N Dawe, J Hammond, Ali F Mahmoud, I McPherson, C Mellor, J Moir, S Pandanaboyana, J Powell, B Rai, A Rogers, C Roy, A Sachdeva, C Saleh, S Tingle, T Williams, J Manickavasagam, C McDonald, N McGrath, N McSorley, K Ragupathy, L Ramsay, A Solth, O Kakisi, K Seebah, I Shaikh, L Sreedharan, M Youssef, J Shah, P Ameerally, N McLarty, S Mills, A Shenfine, K Sahnan, J Abu, E Addae-Boateng, D Bratt, L Brock, N Burnside, S Cadwell-Sneath, K Gajjar, C Gan, C Grundy, K Hallam, K Hassell, M Hawari, A Joshi, H Khout, K Konstantinidi, Rxn Lee, D Nunns, R Schiemer, T Walton, H Weaver, L Whisker, K Williamson, J McVeigh, R Myatt, M A Williams, R Kaur, E Leung, S Sundar, M Michel, S Patil, S Ravindran, J Sarveswaran, L Scott, M Edmond, E King, M Almond, A Bhangu, O Breik, L D Cato, A Desai, S Ford, E Griffiths, M Idle, M Kamal, A Kisiel, R Kulkarni, Jkc Mak, T Martin, P Nankivell, A Parente, S Parmar, A M Pathanki, L Phelan, P Praveen, S Saeed, N Sharma, J Singh, F Tirotta, D Vijayan, A Geddes, J McCaul, J McMahon, A H Khan, F Khan, A Mansuri, S Mukherjee, M Patel, M Sarigul, S Singh, K L Tan, A Woodham, A Adiamah, H Brewer, A Chowdhury, J Evans, D Humes, J Jackman, A Koh, C Lewis-Lloyd, O Oyende, J Reilly, D Worku, P Cool, G Cribb, K Shepherd, C Bisset, S Moug, N Elson, G Faulkner, P Saleh, C Underwood, G Brixton, L Findlay, T Klatte, A Majkowska, J Manson, R Potter, A Bhalla, Z Chia, P Daliya, A Goyal, E Grimley, A Hamad, A Kumar, F L Malcolm, E Theophilidou, J Bowden, N Campain, I Daniels, C Evans, G Fowler, J John, L Massey, F McDermott, J McGrath, A McLennan, M Ng, J Pascoe, N Rajaretnam, S Bulathsinhala, B Davidson, G Fusai, C Hidalgo Salinas, N Machairas, T Pissanou, J M Pollok, D A Raptis, F Soggiu, H Tzerbinis, S E Xyda, A Beamish, E Davies, R Foulkes, D Magowan, H Nassa, R Ooi, C Price, L Smith, F Solari, A Tang, G Williams, Y Al-Tamimi, A Bacon, N Beasley, D Chew, M Crank, N Ilenkovan, M Macdonald, B Narice, O Rominiyi, A Thompson, I Varley, T Drake, E Harrison, G Linder, J Mayes, R McGregor, R Skipworth, V Zamvar, E Davies, P Hawkin, T Raymond, O Ryska, R Baron, D Dunne, S Gahunia, C Halloran, N Howes, R McKinney, F McNicol, J Russ, P Szatmary, J R Tan, A Thomas, P Whelan, A Anzak, A Banerjee, O Fuwa, F Hughes, J D Jayasinghe, C Knowles, H Kocher, I Leal Silva, F S Ledesma, A Minicozzi, L Navaratne, R Rahman, R Ramamoorthy, C Sohrabi, M Thaha, B Thakur, M Venn, V Yip, R Baumber, J Parry, S Evans, L Jeys, G Morris, M Parry, J Stevenson, N Ahmadi, G Aresu, Z M Barrett-Brown, A S Coonar, H Durio Yates, D Gearon, J Hogan, M King, A Peryt, I S Pradeep, C Smith, M Adishesh, R Atherton, K Baxter, M Brocklehurst, M Chaudhury, N Krishnamohan, J McAleer, G Owens, E Parkin, P Patkar, I Phang, A Aladeojebi, M Ali, B Barmayehvar, A Gaunt, M Gowda, E Halliday, M Kitchen, F Mansour, M Thomas, D Zakai, N Abbassi-Ghadi, H Assalaarachchi, A Currie, M Flavin, A Frampton, M Hague, C Hammer, J Hopper, J Horsnell, S Humphries, A Kamocka, T K Madhuri, S Preston, P Singh, J Stebbing, A Tailor, D Walker, F Aljanadi, M Jones, P Mhandu, C O'Donnell, R Turkington, Z Al-Ishaq, S Bhasin, A S Bodla, A Burahee, A Crichton, R Fossett, N Pigadas, S Pickford, E Rahman, D Snee, R Vidya, N Yassin, F Colombo, D Fountain, M T Hasan, K Karabatsou, R Laurente, O Pathmanaban, A Al-Mukhtar, S Brown, J Edwards, A Giblin, C Kelty, M Lee, G Lye, T Newman, A Sharkey, C Steele, N Sureshkumar Shah, E Whitehall, R Athwal, A Baker, L Jones, C Konstantinou, S Ramcharan, S Singh, J Vatish, R Wilkin, M Ethunandan, G K Sekhon, H Shields, R Singh, F Wensley, S Lawday, A Lyons, T Abbott, S Anwar, K Ghufoor, C Sohrabi, E Chung, R Hagger, A Hainsworth, A Karim, H Owen, A Ramwell, K Williams, C Baker, A Davies, J Gossage, M Kelly, W Knight, J Hall, G Harris, G James, C Kang, D J Lin, A D Rajgor, T Royle, R Scurrah, B Steel, L J Watson, D Choi, R Hutchison, A Jain, V Luoma, H Marcus, R May, A Menon, B Pramodana, L Webber, I A Aneke, P Asaad, B Brown, J Collis, S Duff, A Khan, F Moura, B Wadham, H Warburton, T Elmoslemany, M Jenkinson, C Millward, R Zakaria, S Mccluney, C Parmar, S Shah, J Allison, M S Babar, B Collard, S Goodrum, K Lau, A Patel, R Scott, E Thomas, H Whitmore, D Balasubramaniam, B Jayasankar, S Kapoor, A Ramachandran, A Elhamshary, Smb Imam, K Kapriniotis, V Kasivisvanathan, J Lindsay, S Rakhshani-Moghadam, N Beech, M Chand, L Green, N Kalavrezos, H Kiconco, R McEwen, C Schilling, D Sinha, J Pereca, J Singh, S Chopra, D Egbeare, R Thomas, T Combellack, Sef Jones, M Kornaszewska, M Mohammed, A Sharma, G Tahhan, V Valtzoglou, J Williams, P Eskander, K Gash, L Gourbault, M Hanna, T Maccabe, C Newton, J Olivier, S Rozwadowski, E Teh, D West, H Al-Omishy, M Baig, H Bates, G Di Taranto, K Dickson, N Dunne, C Gill, D Howe, D Jeevan, A Khajuria, K Martin-Ucar AMcEvoy, P Naredla, V Ng, S Robertson, M Sait, D R Sarma, S Shanbhag, T Shortland, S Simmonds, J Skillman, N Tewari, G Walton, M A Akhtar, A Brunt, J McIntyre, K Milne, M M Rashid, A Sgro, K E Stewart, A Turnbull, M Aguilar Gonzalez, S Talukder, C Boyle, D Fernando, K Gallagher, A Laird, D Tham, M Bath, P Patki, C Sohrabi, C Tanabalan, T Arif, C Magee, T Nambirajan, S Powell, R Vinayagam, I Flindall, A Hanson, V Mahendran, S Green, M Lim, L MacDonald, V Miu, L Onos, K Sheridan, R Young, F Alam, O Griffiths, C Houlden, R Jones, V S Kolli, A K Lala, S Leeson, R Peevor, Z Seymour, L Chen, E Henderson, A Loehrer, K Brown, D Fleming, A Haynes, C Heron, C Hill, H Kay, E Leede, K McElhinney, K Olson, E C Osterberg, C Riley, P Srikanth, M Thornhill, D Blazer, G DiLalla, E S Hwang, W Lee, M Lidsky, J Plichta, L Rosenberger, R Scheri, K Shah, K Turnage, J Visgauss, S Zani, J Farma, J Clark, D Kwon, E Etchill, H E Gabre-Kidan AJenny, A Kent, M Ladd, C Long, H Malapati, A Margalit, S Rapaport, J Rose, K Stevens, L Tsai, D Vervoort, P Yesantharao, A Dehal, D Klaristenfeld, K Huynh, L Brown, I Ganly, J Mullinax, N Gusani, J Hazelton, J Maines, J S Oh, A Ssentongo, P Ssentongo, M Azam, A Choudhry, W Marx, J Fleming, A Fuson, J Gigliotti, A Ovaitt, Y Ying, M K Abel, V Andaya, K Bigay, M A Boeck, L Chen, H Chern, C Corvera, I El-Sayed, A Glencer, P Ha, Bcs Hamilton, C Heaton, K Hirose, D M Jablons, K Kirkwood, L Z Kornblith, J R Kratz, R Lee, P N Miller, E Nakakura, B Nunez-Garcia, R O'Donnell, D Ozgediz, P Park, B Robinson, A Sarin, B Sheu, M Varma, K Wai, R Wustrack, M J Xu, D Beswick, J Goddard, J Manor, J Song, T Fullmer, C Gaskill, N Gross, K Kiong, C L Roland, S N Zafar, M Abdallah, A Abouassi, M Almasri, G Kulkarni, H Marwan, M Mehdi, S Aoun, V S Ban, H H Batjer, J Caruso, D Abbott, A Acher, T Aiken, J Barrett, E Foley, P Schwartz, S N Zafar, A Hawkins, A Maiga, J Laufer, S Scasso
Subjects: Aged, 80 and over, Male, Critical Care, SARS-CoV-2, International Cooperation, COVID-19, Middle Aged, Cohort Studies, Logistic Models, Postoperative Complications, Elective Surgical Procedures, Neoplasms, Outcome Assessment, Health Care, Humans, Female, Epidemics, Aged
Abstract: PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
Published: 2021

49. [SARS-CoV-2 Infections and Clinical Consequences in a Cohort of Solid Organ Transplant Recipients during the first Wave in Germany - a Single Centre Survey and a Case Report]

Author: Linda, Brake, Markus W, Löffler, Magdalena, Gründl, Anna, Grishina, Helene, Haeberle, Christoph, Berg, Martina, Guthoff, Alfred, Königsrainer, Silvio, Nadalin, and Markus, Quante
Subjects: SARS-CoV-2, Germany, Communicable Disease Control, COVID-19, Humans, Organ Transplantation
Abstract: The SARS-CoV-2 pandemic has caused an unprecedented global health crisis, with exceptionally high mortality rates in high-risk groups of affected patients. It is alarming that a steadily increasing number of clinical reports on outcomes of COVID-19 in solid organ transplant (SOT) recipients suggests a detrimental impact linked to high overall mortality. However, systematic data on SARS-CoV-2 infections in SOT recipients in Germany are still scarce.We conducted a survey on SARS-CoV-2 infection status among 387 SOT recipients treated at our centre during the past 5 years - located in a severely affected region in Germany. The survey was sent out two months after the first SARS CoV-2 outbreak in our region had resulted in government-imposed lockdown measures.An incidence rate of 0.4% SARS-CoV-2-positive SOT recipients was determined in our cohort, in line with reported local infection rates in the general population at this time. However, the only SARS CoV-2 infection known to us within this group of patients led to severe morbidity - resulting in prolonged mechanical ventilation, hospitalisation 60 days and finally in irreversible loss of graft function.Our data demonstrate that SOT recipients are at equal risk for SARS-CoV-2 infections when compared to the general population, while SARS-CoV-2 infections in SOT recipients seem to be associated with deleterious clinical consequences.Die SARS-CoV-2-Pandemie hat zu einer globalen Gesundheitskrise mit hohen Mortalitätsraten insbesondere bei Betroffenen in Hochrisikogruppen geführt. Eine stetig wachsende Zahl klinischer Fallberichte zeigt die Folgen von COVID-19 bei Patienten nach solider Organtransplantation (SOT) und deutet auf schwerwiegende klinische Auswirkungen und eine insgesamt hohe Sterblichkeit in dieser Patientengruppe hin. Systematische Daten zu SARS-CoV-2-Infektionen bei SOT-Empfängern in Deutschland fehlten zunächst jedoch weitgehend.Wir führten deshalb eine Umfrage zum SARS-CoV-2-Infektionsstatus unter insgesamt 387 Patienten nach SOT durch, die in den letzten 5 Jahren an unserem Zentrum transplantiert wurden. Die Umfrage wurde 2 Monate nach dem ersten SARS-CoV-2-Ausbruch in unserer relativ stark betroffenen Region und den damit verbundenen staatlich verordneten Einschränkungen durchgeführt.In unserer SOT-Kohorte wurde eine Rate von 0,4% SARS-CoV-2-positiven Patienten ermittelt, was gut mit den lokalen Infektionsraten in der Allgemeinbevölkerung zum damaligen Zeitpunkt übereinstimmt. Allerdings führte die einzige uns in diesem Kollektiv bekannt gewordene SARS-CoV-2-Infektion zu schwerer Morbidität mit verlängerter mechanischer Beatmung, einem Krankenhausaufenthalt 60 Tage und resultierte letztlich im irreversiblen Verlust der Transplantatfunktion.Unsere Daten zeigen, dass SOT-Empfänger im Vergleich zur Allgemeinbevölkerung zwar ein vergleichbares Risiko für eine SARS-CoV-2-Infektion haben, diese jedoch mit der Gefahr von schwerwiegenderen Verläufen assoziiert zu sein scheint.
Published: 2021

50. Revisited Upper Reference Limits for Highly Sensitive Cardiac Troponin T in Relation to Age, Sex, and Renal Function

Author: Ulrich Laufs, Rolf Wachter, Martin Federbusch, Christiane Gärtner, Thorsten Kaiser, Maria Inês Schmidt, Romy Langhammer, Kerstin Wirkner, Markus W. Löffler, and Berend Isermann
Subjects: medicine.medical_specialty, Percentile, Cardiac troponin, Population, Renal function, Article, chemistry.chemical_compound, Internal medicine, medicine, ddc:610, education, Creatinine, education.field_of_study, biology, business.industry, troponin, General Medicine, cardiac markers, reference intervals, Troponin, Highly sensitive, chemistry, Cohort, biology.protein, Cardiology, Medicine, business
Abstract: (1) Background: Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay is generally applied, irrespective of age, renal function, or sex. We aimed to identify age-adjusted and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiac diseases. (2) Methods: We included 5428 subjects of the population-based LIFE-Adult cohort, free of diagnosed cardiac diseases. Sex-adjusted and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained. (3) Results: The hs-cTnT values were higher in men of all age groups. In both sexes, an increasing age positively correlated with higher hs-cTnT values. Hs-cTnT weakly correlated with serum creatinine. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine on hs-cTnT. In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied thresholds. (4) Conclusion: Age and sex have a major impact on the serum concentration of hs-cTnT, while renal function does not. We propose to consider age-adjusted and sex-adjusted reference values.
Published: 2021

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