المؤلفون: Henning Plage, Kira Furlano, Jörg Neymeyer, Sarah Weinberger, Benedikt Gerdes, Mandy Hubatsch, Bernhard Ralla, Antonia Franz, Annika Fendler, Michela deMartino, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Martina Kluth, Maximilian Lennartz, Niclas C. Blessin, Andreas H. Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Krystian Kaczmarek, Thorsten Ecke, Steffen Hallmann, Stefan Koch, Nico Adamini, Sarah Minner, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Henrik Zecha, Marcin Slojewski

المصدر: BJUI Compass, Vol 5, Iss 6, Pp 585-592 (2024)

مصطلحات موضوعية: bladder cancer, CEA, CEACAM5, immunohistochemistry, prognosis, tissue microarray, Diseases of the genitourinary system. Urology, RC870-923

الوصف: Abstract Objectives Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low‐grade, 32.0% of 178 pTaG2 high‐grade, and 43.0% of 93 pTaG3 tumours (p 0.25). Conclusion CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2–4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2–4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti‐CEA drugs.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2688-4526Test

الوصول الحر: https://doaj.org/article/81a61db9b6264355b1ed85e97fb6d1feTest

المؤلفون: Henning Plage, Kira Furlano, Sebastian Hofbauer, Sarah Weinberger, Bernhard Ralla, Antonia Franz, Annika Fendler, Michela de Martino, Florian Roßner, Sefer Elezkurtaj, Martina Kluth, Maximilian Lennartz, Niclas C. Blessin, Andreas H. Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Steffen Hallmann, Stefan Koch, Nico Adamini, Henrik Zecha, Sarah Minner, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Simon Schallenberg

المصدر: BMC Urology, Vol 24, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: PD-L1, Urothelial bladder carcinomas, Tissue microarray, Immunohistochemistry, Diseases of the genitourinary system. Urology, RC870-923

الوصف: Abstract Background A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. Methods To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. Results Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2–4) carcinomas (29.3%; p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2490Test

الوصول الحر: https://doaj.org/article/2e11c11592e44f26b250abef630710aaTest

المؤلفون: Tonina T. Mueller, Mona Pilartz, Manovriti Thakur, Torben LangHeinrich, Junfu Luo, Rebecca Block, Jonathan K.L. Hoeflinger, Sarah Meister, Flavio Karaj, Laura Garcia Perez, Rupert Öllinger, Thomas Engleitner, Jakob Thoss, Michael Voelkl, Claudia Tersteeg, Uwe Koedel, Alexander Zigman Kohlmaier, Daniel Teupser, Malgorzata Wygrecka, Haifeng Ye, Klaus T. Preissner, Helena Radbruch, Sefer Elezkurtaj, Matthias Mack, Philipp von Hundelshausen, Christian Weber, Steffen Massberg, Christian Schulz, Roland Rad, Samuel Huber, Hellen Ishikawa-Ankerhold, Bernd Engelmann

المصدر: Haematologica, Vol 999, Iss 1 (2024)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.

وصف الملف: electronic resource

العلاقة: https://haematologica.org/article/view/11539Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test

الوصول الحر: https://doaj.org/article/4839f9e3a00e42f59cb668d05a73ce41Test

المؤلفون: Jan H. Müller, Henning Plage, Sefer Elezkurtaj, Tim Mandelkow, Zhihao Huang, Magalie C. J. Lurati, Jonas B. Raedler, Nicolaus F. Debatin, Eik Vettorazzi, Henrik Samtleben, Sebastian Hofbauer, Kira Furlano, Jörg Neymeyer, Irena Goranova, Bernhard Ralla, Sarah Weinberger, David Horst, Florian Roßner, Simon Schallenberg, Andreas H. Marx, Margit Fisch, Michael Rink, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Steffen Hallmann, Stefan Koch, Nico Adamini, Maximilian Lennartz, Sarah Minner, Ronald Simon, Guido Sauter, Henrik Zecha, Thorsten Schlomm, Elena Bady

المصدر: Frontiers in Oncology, Vol 13 (2024)

مصطلحات موضوعية: TROP2, EpCAM, muscle invasive urothelial cancer, multiplex fluorescence immunohistochemistry, bladder cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: IntroductionTrophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. MethodsTo evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. ResultsThe staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2023.1342367/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/e1665b34d1bc44738c48bdeeea0208d5Test

المؤلفون: Ronja Mothes, Anna Pascual-Reguant, Ralf Koehler, Juliane Liebeskind, Alina Liebheit, Sandy Bauherr, Lars Philipsen, Carsten Dittmayer, Michael Laue, Regina von Manitius, Sefer Elezkurtaj, Pawel Durek, Frederik Heinrich, Gitta A. Heinz, Gabriela M. Guerra, Benedikt Obermayer, Jenny Meinhardt, Jana Ihlow, Josefine Radke, Frank L. Heppner, Philipp Enghard, Helena Stockmann, Tom Aschman, Julia Schneider, Victor M. Corman, Leif E. Sander, Mir-Farzin Mashreghi, Thomas Conrad, Andreas C. Hocke, Raluca A. Niesner, Helena Radbruch, Anja E. Hauser

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-16 (2023)

مصطلحات موضوعية: Science

الوصف: Infection with SARS-CoV-2 has been linked with substantive inflammation, lung pathology and development of COVID-19. Here the authors spatially associate CCL18 and CCL21 in distinct tissue niches with lung pathology of severe COVID-19.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/1b2247b6d5234d329b89d09ddd2a8d84Test

المؤلفون: Janine Büttner, Elisabeth Blüthner, Sophie Greif, Anja Kühl, Sefer Elezkurtaj, Jan Ulrich, Sebastian Maasberg, Christoph Jochum, Frank Tacke, Ulrich-Frank Pape

المصدر: Nutrients, Vol 15, Iss 19, p 4220 (2023)

مصطلحات موضوعية: short bowel syndrome, chronic intestinal failure, glucagon-like peptide-2, teduglutide, intestinal permeability, Nutrition. Foods and food supply, TX341-641

الوصف: Introduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Methods: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. Results: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Conclusions: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6643/15/19/4220Test; https://doaj.org/toc/2072-6643Test

الوصول الحر: https://doaj.org/article/e417db28f76b45a58f4977d202090119Test

المؤلفون: Jana Ihlow, Alexander Seelhoff, Victor M. Corman, Achim D. Gruber, Simon Dökel, Jenny Meinhardt, Helena Radbruch, Ernst Späth-Schwalbe, Sefer Elezkurtaj, David Horst, Hermann Herbst

المصدر: BMC Infectious Diseases, Vol 21, Iss 1, Pp 1-6 (2021)

مصطلحات موضوعية: COVID-19, SARS-CoV-2, Bile duct, Hepatitis, Case report, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presentation Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). Conclusion Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2334Test

الوصول الحر: https://doaj.org/article/f9220960827e48ff8c273fe345decd0eTest

المؤلفون: Jan Matthias Kruse, Daniel Zickler, Willie M. Lüdemann, Sophie K. Piper, Inka Gotthardt, Jana Ihlow, Selina Greuel, David Horst, Andreas Kahl, Kai-Uwe Eckardt, Sefer Elezkurtaj

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25–17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35–58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/2b1cbf31a5a947619e2f08ce4ee8cea0Test

المؤلفون: Susanne Krasemann, Carsten Dittmayer, Saskia von Stillfried, Jenny Meinhardt, Fabian Heinrich, Kristin Hartmann, Susanne Pfefferle, Edda Thies, Regina von Manitius, Tom Alex David Aschman, Josefine Radke, Anja Osterloh, Simone Schmid, Eva Miriam Buhl, Jana Ihlow, Frank Dubois, Viktor Arnhold, Sefer Elezkurtaj, David Horst, Andreas Hocke, Sara Timm, Sebastian Bachmann, Victor Corman, Hans-Hilmar Goebel, Jakob Matschke, Stephanie Stanelle-Bertram, Gülsah Gabriel, Danielle Seilhean, Homa Adle-Biassette, Benjamin Ondruschka, Matthias Ochs, Werner Stenzel, Frank L. Heppner, Peter Boor, Helena Radbruch, Michael Laue, Markus Glatzel

المصدر: EBioMedicine, Vol 83, Iss , Pp 104193- (2022)

مصطلحات موضوعية: SARS-CoV-2, COVID-19, Autopsy, Immunohistochemistry, Electron microscopy, Pathology, Medicine, Medicine (General), R5-920

الوصف: Summary: Background: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing. Methods: We assessed publications using IHC and EM for SARS-CoV-2 detection in autopsy tissues. We systematically evaluated commercially available antibodies against the SARS-CoV-2 proteins in cultured cell lines and COVID-19 autopsy tissues. In a multicentre study, we evaluated specificity, reproducibility, and inter-observer variability of SARS-CoV-2 IHC. We correlated RT-qPCR viral tissue loads with semiquantitative IHC scoring. We used qualitative and quantitative EM analyses to refine criteria for ultrastructural identification of SARS-CoV-2. Findings: Publications show high variability in detection and interpretation of SARS-CoV-2 abundance in autopsy tissues by IHC or EM. We show that IHC using antibodies against SARS-CoV-2 nucleocapsid yields the highest sensitivity and specificity. We found a positive correlation between presence of viral proteins by IHC and RT-qPCR-determined SARS-CoV-2 viral RNA load (N= 35; r=-0.83, p-value

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396422003747Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/8c3f588c9dc544439b18fd7f7d5e9f6bTest

المؤلفون: Selina Greuel, Jana Ihlow, Mihnea-Paul Dragomir, Simon Streit, Victor Max Corman, Linus Haberbosch, David Winkler, Jenny Meinhardt, Tom Aschman, Julia Schneider, Iryna Trotsyuk, Catarina Alisa Kunze, Lukas Maurer, Helena Radbruch, Frank L. Heppner, David Horst, Sefer Elezkurtaj

المصدر: International Journal of Infectious Diseases, Vol 108, Iss , Pp 274-281 (2021)

مصطلحات موضوعية: COVID-19, SARS-CoV-2, Cause of death, Autopsy, Younger, Infectious and parasitic diseases, RC109-216

الوصف: Objectives: Studies on coronavirus disease 2019 (COVID-19) usually focus on middle-aged and older adults. However, younger patients may present with severe COVID-19 with potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of the underlying pathomechanisms is of utmost importance. Methods: Our study investigated relevant, pre-existing medical conditions, clinical histories, and autopsy findings, together with SARS-CoV-2-RNA, determined by qPCR, and laboratory data in six COVID-19 decedents aged 50 years or younger, who were autopsied at the Charité University Hospital. Results: From a total of 76 COVID-19 patients who underwent an autopsy at our institution, six (7.9%) were 50 years old or younger. Most of these younger COVID-19 decedents presented with pre-existing medical conditions prior to SARS-CoV-2 infection. These included overweight and obesity, arterial hypertension, asthma, and obstructive sleep apnea, as well as graft-versus-host disease following cancer and bone marrow transplantation. Furthermore, clinical histories and autopsy results revealed a disproportionally high prevalence of thromboembolism and ischemic organ damage in this patient cohort. Histopathology and laboratory results indicated coagulopathies, signs of immune dysregulation, and liver damage. Conclusions: In conclusion, pre-existing health conditions may increase the risk of severe and fatal COVID-19 in younger patients, who may be especially prone to developing thromboembolic complications, immune dysregulation, and liver damage.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1201971221004720Test; https://doaj.org/toc/1201-9712Test

الوصول الحر: https://doaj.org/article/0595539e3f164cfe9a2ebafdf53c9a07Test