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Article: Pathologie von Infektionskrankheiten.

Turek, Daniel / Graber, Anne / Nienhold, Ronny / Cathomas, Gieri

Therapeutische Umschau. Revue therapeutique

2020 Volume 76, Issue 7, Page(s) 391–396

Abstract: Pathology of infectious ... ...

Title translation	Pathology of infectious diseases.
Abstract	Pathology of infectious diseases
MeSH term(s)	Communicable Diseases/pathology ; Humans ; Pathology, Molecular
Language	German
Publishing date	2020-01-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	82044-1
ISSN	1664-2864 ; 0040-5930
ISSN (online)	1664-2864
ISSN	0040-5930
DOI	10.1024/0040-5930/a001120
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Article ; Online: Somatic variant profiling in chronic phase pediatric chronic myeloid leukemia.

Behrens, Yvonne Lisa / Gaschler, Laura / Nienhold, Ronny / Reinkens, Thea / Schirmer, Elke / Knöß, Sabine / Strasser, Renate / Sembill, Stephanie / Wotschofsky, Zofia / Suttorp, Meinolf / Krumbholz, Manuela / Schlegelberger, Brigitte / Metzler, Markus / Göhring, Gudrun / Karow, Axel

Haematologica

2024 Volume 109, Issue 3, Page(s) 942–947

MeSH term(s)	Child ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
Language	English
Publishing date	2024-03-01
Publishing country	Italy
Document type	Letter
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283800
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Article ; Online: Impact of Clonal Architecture on Clinical Course and Prognosis in Patients With Myeloproliferative Neoplasms.

Luque Paz, Damien / Bader, Michael S / Nienhold, Ronny / Rai, Shivam / Almeida Fonseca, Tiago / Stetka, Jan / Hao-Shen, Hui / Mild-Schneider, Gabriele / Passweg, Jakob R / Skoda, Radek C

HemaSphere

2023 Volume 7, Issue 5, Page(s) e885

Abstract: Myeloproliferative neoplasms (MPNs) are caused by a somatic gain-of-function mutation in 1 of the 3 disease driver ... ...

Abstract	Myeloproliferative neoplasms (MPNs) are caused by a somatic gain-of-function mutation in 1 of the 3 disease driver genes
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000885
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Article: Pathologie von Infektionskrankheiten

Turek, Daniel / Graber, Anne / Nienhold, Ronny / Cathomas, Gieri

Therapeutische Umschau

2019 Volume 76, Issue 7, Page(s) 391–396

Abstract: Die gewebebasierte histopathologische und molekularpathologische Diagnostik von Infektionskrankheiten ist ein sehr spannendes interdisziplinäres Feld, das in der Wahrnehmung nicht nur der fachfremden Kolleginnen und Kollegen manchmal etwas im Schatten ... ...

Abstract	Die gewebebasierte histopathologische und molekularpathologische Diagnostik von Infektionskrankheiten ist ein sehr spannendes interdisziplinäres Feld, das in der Wahrnehmung nicht nur der fachfremden Kolleginnen und Kollegen manchmal etwas im Schatten der Tumordiagnostik steht.
Keywords	Diagnostik ; Zusatzuntersuchungen ; Patientenbetreuung
Language	German
Document type	Article
ZDB-ID	82044-1
ISSN	1664-2864 ; 0040-5930
ISSN (online)	1664-2864
ISSN	0040-5930
Database	bibnet.org

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Article: Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach.

Daun, Till / Nienhold, Ronny / Paasinen-Sohns, Aino / Frank, Angela / Sachs, Melanie / Zlobec, Inti / Cathomas, Gieri

Cancers

2021 Volume 13, Issue 15

Abstract: Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote ...

Abstract	Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes only partially overlap. In addition, the classifications are based on complex and cost-intensive technologies, which are hardly feasible for everyday practice. Therefore, simplified approaches using immunohistochemistry (IHC), in situ hybridization (ISH) as well as commercially available next generation sequencing (NGS) have been considered for routine use. In the present study, we screened 115 GAC by IHC for p53, MutL Homolog 1 (MLH1) and E-cadherin and performed ISH for Epstein-Barr virus (EBV). In addition, sequencing by NGS for TP53 and tumor associated genes was performed. With this approach, we were able to define five subtypes of GAC: (1) Microsatellite Instable (MSI), (2) EBV-associated, (3) Epithelial Mesenchymal Transition (EMT)-like, (4) p53 aberrant tumors surrogating for chromosomal instability and (5) p53 proficient tumors surrogating for genomics stable cancers. Furthermore, by considering lymph node metastasis in the p53 aberrant GAC, a better prognostic stratification was achieved which finally allowed us to separate the GAC highly significant in a group with poor and good-to-intermediate prognosis, respectively. Our data show that molecular classification of GAC can be achieved by using commercially available assays including IHC, ISH and NGS. Furthermore, we present an integrative workflow, which has the potential to overcome the uncertainty resulting from discrepancies from existing classification schemes.
Language	English
Publishing date	2021-07-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13153722
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Article ; Online: Unbiased screen for pathogens in human paraffin-embedded tissue samples by whole genome sequencing and metagenomics.

Nienhold, Ronny / Mensah, Nadine / Frank, Angela / Graber, Anne / Koike, Jacqueline / Schwab, Nathalie / Hernach, Claudia / Zsikla, Veronika / Willi, Niels / Cathomas, Gieri / Hamelin, Baptiste / Graf, Susanne / Junt, Tobias / Mertz, Kirsten D

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 968135

Abstract: Identification of bacterial pathogens in formalin fixed, paraffin embedded (FFPE) tissue samples is limited to targeted and resource-intensive methods such as sequential PCR analyses. To enable unbiased screening for pathogens in FFPE tissue samples, we ... ...

Abstract	Identification of bacterial pathogens in formalin fixed, paraffin embedded (FFPE) tissue samples is limited to targeted and resource-intensive methods such as sequential PCR analyses. To enable unbiased screening for pathogens in FFPE tissue samples, we established a whole genome sequencing (WGS) method that combines shotgun sequencing and metagenomics for taxonomic identification of bacterial pathogens after subtraction of human genomic reads. To validate the assay, we analyzed more than 100 samples of known composition as well as FFPE lung autopsy tissues with and without histological signs of infections. Metagenomics analysis confirmed the pathogenic species that were previously identified by species-specific PCR in 62% of samples, showing that metagenomics is less sensitive than species-specific PCR. On the other hand, metagenomics analysis identified pathogens in samples, which had been tested negative for multiple common microorganisms and showed histological signs of infection. This highlights the ability of this assay to screen for unknown pathogens and detect multi-microbial infections which is not possible by histomorphology and species-specific PCR alone.
MeSH term(s)	Bacteria/genetics ; Formaldehyde ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/methods ; Paraffin Embedding ; Whole Genome Sequencing
Chemical Substances	Formaldehyde (1HG84L3525)
Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.968135
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Article: COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections.

Schwab, Nathalie / Nienhold, Ronny / Henkel, Maurice / Baschong, Albert / Graber, Anne / Frank, Angela / Mensah, Nadine / Koike, Jacqueline / Hernach, Claudia / Sachs, Melanie / Daun, Till / Zsikla, Veronika / Willi, Niels / Junt, Tobias / Mertz, Kirsten D

Frontiers in medicine

2022 Volume 9, Page(s) 868954

Abstract: Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we ...

Abstract	Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.
Language	English
Publishing date	2022-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.868954
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Article ; Online: COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections

Nathalie Schwab / Ronny Nienhold / Maurice Henkel / Albert Baschong / Anne Graber / Angela Frank / Nadine Mensah / Jacqueline Koike / Claudia Hernach / Melanie Sachs / Till Daun / Veronika Zsikla / Niels Willi / Tobias Junt / Kirsten D. Mertz

Frontiers in Medicine, Vol

2022 Volume 9

Abstract	Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.
Keywords	COVID-19 ; SARS-CoV-2 ; autopsy ; mortality ; respiratory failure ; infection ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study.

Sobottka, Bettina / Nienhold, Ronny / Nowak, Marta / Hench, Juergen / Haeuptle, Pirmin / Frank, Angela / Sachs, Melanie / Kahraman, Abdullah / Moch, Holger / Koelzer, Viktor H / Mertz, Kirsten D

Journal of immunotherapy (Hagerstown, Md. : 1997)

2021 Volume 45, Issue 1, Page(s) 35–42

Abstract: Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation ... ...

Abstract	Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified decreased frequencies of CD8+ tumor-infiltrating T cells and TLS, and a decreased expression of PD-L1 in ICI responders when compared with nonresponders. However, neither tumor-specific genetic alterations nor gene expression profiles correlated with response to ICI or the observed immune features. Our results underline the challenge to stratify ccRCC patients for immunotherapy based on routinely available pathologic primary tumor material, even with advanced technologies. Our findings emphasize the analysis of pretreated metastatic tissue in line with recent observations describing treatment effects on the tumor microenvironment. In addition, our data call for further investigation of additional parameters in a larger ccRCC cohort to understand the mechanistic implications of the observed differences in tumor-infiltrating CD8+ T cells, TLS, and PD-L1 expression.
MeSH term(s)	B7-H1 Antigen ; CD8-Positive T-Lymphocytes ; Carcinoma, Renal Cell/therapy ; Humans ; Immunotherapy ; Kidney Neoplasms/therapy ; Lymphocytes, Tumor-Infiltrating ; Tumor Microenvironment
Chemical Substances	B7-H1 Antigen
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000387
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Article ; Online: Characterisation of cardiac pathology in 23 autopsies of lethal COVID-19.

Haslbauer, Jasmin D / Tzankov, Alexandar / Mertz, Kirsten D / Schwab, Nathalie / Nienhold, Ronny / Twerenbold, Raphael / Leibundgut, Gregor / Stalder, Anna K / Matter, Matthias / Glatz, Katharina

The journal of pathology. Clinical research

2021 Volume 7, Issue 4, Page(s) 326–337

Abstract: While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from ...

Abstract	While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from 23 autopsies of COVID-19 patients, comparing the findings with control tissue. Myocardium from autopsies of COVID-19 patients was categorised into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive (n = 14) or negative (n = 9) based on the presence of viral RNA as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Control tissue was selected from autopsies without COVID-19 (n = 10) with similar clinical sequelae. Histological characteristics were scored by ordinal and/or categorical grading. Five RT-PCR-positive cases underwent in situ hybridisation (ISH) for SARS-CoV-2. Patients with lethal COVID-19 infection were mostly male (78%) and had a high incidence of hypertension (91%), coronary artery disease (61%), and diabetes mellitus (48%). Patients with positive myocardial RT-PCR died earlier after hospital admission (5 versus 12 days, p < 0.001) than patients with negative RT-PCR. An increased severity of fibrin deposition, capillary dilatation, and microhaemorrhage was observed in RT-PCR-positive myocardium than in negatives and controls, with a positive correlation amongst these factors All cases with increased cardioinflammatory infiltrate, without myocyte necrosis (n = 4) or with myocarditis (n = 1), were RT-PCR negative. ISH revealed positivity of viral RNA in interstitial cells. Myocardial capillary dilatation, fibrin deposition, and microhaemorrhage may be the histomorphological correlate of COVID-19-associated coagulopathy. Increased cardioinflammation including one case of myocarditis was only detected in RT-PCR-negative hearts with significantly longer hospitalisation time. This may imply a secondary immunological response warranting further characterisation.
MeSH term(s)	Adult ; Autopsy/methods ; COVID-19/complications ; COVID-19/pathology ; COVID-19/virology ; Female ; Humans ; Male ; Middle Aged ; Myocarditis/etiology ; Myocarditis/pathology ; Myocardium/pathology ; RNA, Viral/genetics ; Respiratory System/pathology ; Respiratory System/virology ; SARS-CoV-2/pathogenicity
Chemical Substances	RNA, Viral
Language	English
Publishing date	2021-04-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814357-7
ISSN	2056-4538 ; 2056-4538
ISSN (online)	2056-4538
ISSN	2056-4538
DOI	10.1002/cjp2.212
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