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  • 1
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    Online Resource
    Metastatic Pheochromocytoma and Paraganglioma: Somatostatin Receptor 2 Expression, Genetics, and Therapeutic Responses
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 10 ( 2023-09-18), p. 2676-2685
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 10 ( 2023-09-18), p. 2676-2685
    Abstract: Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)–dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. Objective Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. Methods Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical–pathological features of PPGLs. Results Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P & lt; .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line “cold” somatostatin analogs 100% (n = 6, n = 3 SDHx). Conclusion SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor–based therapies in metastatic PPGLs.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgad166
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 2
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    SARS-CoV-2 leads to a small vessel endotheliitis in the heart
    Elsevier BV ; 2021
    In:  EBioMedicine Vol. 63 ( 2021-01), p. 103182-
    Details
    In: EBioMedicine, Elsevier BV, Vol. 63 ( 2021-01), p. 103182-
    Type of Medium: Online Resource
    ISSN: 2352-3964
    URL: Article
    DOI: 10.1016/j.ebiom.2020.103182
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2799017-5
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  • 3
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    Higher prevalence of pulmonary macrothrombi in SARS‐CoV ‐2 than in influenza A: autopsy results from ‘Spanish flu’ 1918/1919 in Switzerland to Coronavirus disease 2019
    Wiley ; 2021
    In:  The Journal of Pathology: Clinical Research Vol. 7, No. 2 ( 2021-03), p. 135-143
    Details
    In: The Journal of Pathology: Clinical Research, Wiley, Vol. 7, No. 2 ( 2021-03), p. 135-143
    Abstract: Similar to the influenza A pandemic in 1918/1919, the new Coronavirus disease 2019 (COVID‐19) has spread globally. The causes of death in COVID‐19 are frequently compared to a seasonal influenza outbreak. Complete COVID‐19 autopsy studies were almost non‐existent in the first months of the outbreak and are still rare with respect to the number of deaths. It has been recently reported that capillary microthrombi are significantly more prevalent in patients with COVID‐19 than in patients with influenza A. To date, the contribution of macrothrombi, i.e. visible thrombi in pulmonary arteries, to the death of patients with influenza A in comparison to COVID‐19 remains unaddressed. Here, we report autopsy findings in 411 patients who died from the ‘Spanish’ influenza A pandemic between May 1918 and April 1919 at the University Hospital Zurich, Switzerland. We compare these results with influenza A autopsies from 2009 to 2020, other influenza A autopsy series and all COVID‐19 autopsies published to date. No descriptions of any macroscopic thromboembolic events were mentioned in influenza A autopsy reports. In 75 published COVID‐19 autopsies, pulmonary artery thrombosis/embolism was reported in 36%. The direct comparison of macroscopic autopsy findings suggests a significantly greater degree of grossly visible pulmonary macrothrombi in patients with COVID‐19 in comparison to influenza A autopsies even though most patients received empiric thromboprophylaxis. This is consistent with the concept of a SARS‐related de novo coagulopathy with generalised in situ clot formation, which could explain the high incidence of pulmonary thrombosis/embolism with or without underlying deep vein thrombosis and in the absence of a history of venous thromboembolic events.
    Type of Medium: Online Resource
    ISSN: 2056-4538 , 2056-4538
    URL: Issue
    URL: Article
    DOI: 10.1002/cjp2.v7.2
    DOI: 10.1002/cjp2.189
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2814357-7
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  • 4
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-2-9)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-2-9)
    Abstract: Long-term sequelae of coronavirus disease 2019 (COVID-19), including the interaction between persisting viral-RNA and specific tissue involvement, pose a challenging issue. In this study, we addressed the chronological correlation (after first clinical diagnosis and postmortem) between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and organ involvement. Methods The presence of postmortem SARS-CoV-2 RNA from 35 complete COVID-19 autopsies was correlated with the time interval between the first diagnosis of COVID-19 and death and with its relationship to morphologic findings. Results Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be evident up to 40 days after the first diagnosis and can persist to 94 hours after death. Postmortem SARS-CoV-2 RNA was mostly positive in lungs (70%) and trachea (69%), but all investigated organs were positive with variable frequency. Late-stage tissue damage was evident up to 65 days after initial diagnosis in several organs. Positivity for SARS-CoV-2 RNA in pulmonary swabs correlated with diffuse alveolar damage ( p = 0.0009). No correlation between positive swabs and other morphologic findings was present. Cerebral ( p = 0.0003) and systemic hemorrhages ( p = 0.009), cardiac thrombi ( p = 0.04), and ischemic events ( p = 0.03) were more frequent in the first wave, whereas bacterial pneumonia ( p = 0.03) was more prevalent in the second wave. No differences in biometric data, clinical comorbidities, and other autopsy findings were found. Conclusions Our data provide evidence not only of long-term postmortem persisting SARS-CoV-2 RNA but also of tissue damage several weeks after the first diagnosis of SARS-CoV-2 infection. Additional conditions, such as concomitant bacterial pulmonary superinfection, lung aspergillosis, thromboembolic phenomena, and hemorrhages can further worsen tissue damage.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.778489
    DOI: 10.3389/fmed.2022.778489.s001
    DOI: 10.3389/fmed.2022.778489.s002
    DOI: 10.3389/fmed.2022.778489.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 5
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    Bone marrow haematopoiesis in patients with COVID ‐19
    Wiley ; 2023
    In:  Histopathology Vol. 83, No. 4 ( 2023-10), p. 582-590
    Details
    In: Histopathology, Wiley, Vol. 83, No. 4 ( 2023-10), p. 582-590
    Abstract: Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) infection broadly affects organ homeostasis, including the haematopoietic system. Autopsy studies are a crucial tool for investigation of organ‐specific pathologies. Here we perform an in‐depth analysis of the impact of severe coronavirus disease 2019 (COVID‐19) on bone marrow haematopoiesis in correlation with clinical and laboratory parameters. Methods and results Twenty‐eight autopsy cases and five controls from two academic centres were included in the study. We performed a comprehensive analysis of bone marrow pathology and microenvironment features with clinical and laboratory parameters and assessed SARS‐CoV‐2 infection of the bone marrow by quantitative polymerase chain reaction (qPCR) analysis. In COVID‐19 patients, bone marrow specimens showed a left‐shifted myelopoiesis (19 of 28, 64%), increased myeloid–erythroid ratio (eight of 28, 28%), increased megakaryopoiesis (six of 28, 21%) and lymphocytosis (four of 28, 14%). Strikingly, a high proportion of COVID‐19 specimens showed erythrophagocytosis (15 of 28, 54%) and the presence of siderophages (11 of 15, 73%) compared to control cases (none of five, 0%). Clinically, erythrophagocytosis correlated with lower haemoglobin levels and was more frequently observed in patients from the second wave. Analysis of the immune environment showed a strong increase in CD68+ macrophages (16 of 28, 57%) and a borderline lymphocytosis (five of 28, 18%). The stromal microenvironment showed oedema (two of 28, 7%) and severe capillary congestion (one of 28, 4%) in isolated cases. No stromal fibrosis or microvascular thrombosis was found. While all cases had confirmed positive testing of SARS‐CoV‐2 in the respiratory system, SARS‐CoV‐2 was not detected in the bone marrow by high‐sensitivity PCR, suggesting that SARS‐CoV‐2 does not commonly replicate in the haematopoietic microenvironment. Conclusions SARS‐CoV‐2 infection indirectly impacts the haematological compartment and the bone marrow immune environment. Erythrophagocytosis is frequent and associated with lower haemoglobin levels in patients with severe COVID‐19.
    Type of Medium: Online Resource
    ISSN: 0309-0167 , 1365-2559
    URL: Issue
    URL: Article
    DOI: 10.1111/his.v83.4
    DOI: 10.1111/his.14969
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2006447-0
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  • 6
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    Hypoxia and Ezrin Expression in Primary Melanoma Have High Prognostic Relevance
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 18 ( 2022-09-15), p. 10745-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 18 ( 2022-09-15), p. 10745-
    Abstract: Hypoxia affects tumor aggressiveness and activates pathways associated with epithelial mesenchymal transition (EMT) which are crucial for tumor progress. In this study, the correlation of hypoxia and EMT with sentinel lymph node status and tumor-specific survival was investigated in primary melanomas. CD34 for capillary count and Hypoxia inducible factor-1α (HIF-1α) as hypoxia indicators as well as Ezrin and L1-Cell Adhesion Molecule (L1CAM), both critical proteins contributing to EMT, were analyzed using immunohistochemistry in 49 melanoma patients with long follow-up (F/U, mean 110 months; range 12–263 months). We found a significant correlation between Breslow tumor thickness and Ezrin expression (p = 0.018). L1CAM expression in primary melanoma was significantly associated with HIF-1α expression (p 〈 0.0001) and sentinel lymph node metastasis (p = 0.011). Furthermore, low capillary count, reflecting hypoxic condition, was significantly associated with Ezrin expression (p = 0.047) and decreased tumor-specific survival (p = 0.035). In addition, patients with high Ezrin expression in their primary melanoma had a dramatic loss of life early in their F/U period (mean survival time 29 months; range 15–44 month). Our results highlight the relevance of Ezrin, L1CAM and HIF-1α as prognostic markers in melanoma patients. Additionally, we demonstrate that hypoxia in primary melanoma affects EMT and is at least partly responsible for early metastatic dissemination.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231810745
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Online Resource
    Granulomas in bone marrow biopsies: clinicopathological significance and new perspectives
    BMJ ; 2023
    In:  Journal of Clinical Pathology
    Details
    In: Journal of Clinical Pathology, BMJ
    Abstract: Bone marrow granulomas in trephine biopsies are a rare and usually incidental finding. Possible causes include infectious (especially tuberculous and rarer non-tuberculous mycobacteria, but also many other bacterial, viral, fungal and parasitic agents) and non-infectious causes (especially medications, autoimmune disease, sarcoidosis, haematological and non-haematological malignancy). Necrotising granulomas are generally suggestive of an infectious aetiology (tuberculosis being the most common), whereas fibrin ring granulomas are associated with Q-fever and Epstein Barr Virus, although exceptions are possible. Every case suspicious for infectious aetiology should undergo further analysis like special staining (Ziehl-Neelsen for acid-fast rods) or molecular studies. The histomorphology should always be clinically correlated. In cases in which no infectious cause can be identified, untargeted metagenomics may represent a valid diagnostic tool that may become standard in the near future for bone marrow diagnostics. In this review, we have analysed the published data from 1956 up to today, and we report aspects of epidemiology, aetiology, diagnostic algorithms, differential diagnosis and the role of metagenomics in bone marrow biopsies with granulomas.
    Type of Medium: Online Resource
    ISSN: 0021-9746 , 1472-4146
    URL: Article
    DOI: 10.1136/jcp-2023-209104
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2028928-5
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  • 8
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    Lymphoid aggregates in bone marrow: a diagnostic pitfall
    BMJ ; 2022
    In:  Journal of Clinical Pathology Vol. 75, No. 12 ( 2022-12), p. 807-814
    Details
    In: Journal of Clinical Pathology, BMJ, Vol. 75, No. 12 ( 2022-12), p. 807-814
    Abstract: Lymphoid aggregates in bone marrow specimens are a relatively frequent finding that may pose a diagnostic challenge for a pathologist. The distinction between reactive and neoplastic aggregates has significant clinical relevance. Although many testing modalities such as immunohistochemistry, flow cytometry and molecular studies are currently available in clinical laboratories, the appropriate utilisation of these modalities and the awareness of their potential pitfalls are important. When a neoplastic process is ruled out, the significance of benign lymphoid aggregates in bone marrow is often unclear, as they may be associated with a broad spectrum of conditions including infections, autoimmune disorders, medications, or may even be idiopathic. This review focuses on evidence-based criteria that can aid in making the distinction between benign and malignant lymphoid aggregates and discusses the advantages, disadvantages and limits of ancillary tests used for this purpose. Finally, the most common aetiologies of benign lymphoid aggregates and their associations with specific diseases are discussed.
    Type of Medium: Online Resource
    ISSN: 0021-9746 , 1472-4146
    URL: Article
    DOI: 10.1136/jclinpath-2022-208174
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2028928-5
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  • 9
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    Ungewöhnlicher pulmonaler Befund
    EMH Swiss Medical Publishers, Ltd. ; 2022
    In:  Swiss Medical Forum ‒ Schweizerisches Medizin-Forum
    Details
    In: Swiss Medical Forum ‒ Schweizerisches Medizin-Forum, EMH Swiss Medical Publishers, Ltd.
    Type of Medium: Online Resource
    ISSN: 1424-4020
    URL: Article
    DOI: 10.4414/smf.2022.08762
    Language: German
    Publisher: EMH Swiss Medical Publishers, Ltd.
    Publication Date: 2022
    detail.hit.zdb_id: 2059452-5
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  • 10
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    COVID-19 Infections in Gonads: Consequences on Fertility?
    Georg Thieme Verlag KG ; 2022
    In:  Hormone and Metabolic Research Vol. 54, No. 08 ( 2022-08), p. 549-555
    Details
    In: Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 54, No. 08 ( 2022-08), p. 549-555
    Abstract: COVID-19 may influence human fertility and sexuality in several ways. Different cell types in gonads show a constitutive expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), which provide potential entry pathways for SARS-CoV-2. In addition to the biological effects of a COVID-19 infection on the gonads, the impact of the ongoing COVID-19 pandemic on mental health issues and sexual behavior may affect reproduction. This review summarizes the current knowledge on the influence of COVID-19 on the gonads and discusses possible consequences on human fertility. In this context, the close interaction between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis in response to COVID-19-related stress is discussed. Some women noticed changes in their menstrual cycle during the COVID-19 pandemic, which could be due to psychological stress, for example. In addition, occasional cases of reduced oocyte quality and ovarian function are described after COVID-19 infection. In men, COVID-19 may cause a short-term decrease in fertility by damaging testicular tissue and/or impairing spermatogenesis. Moreover, decreased ratio testosterone/LH and FSH/LH in COVID-19 compared to aged-matched healthy men has been reported. Available data do not suggest any effect of the available SARS-CoV-2 vaccines on fertility. The effects of long COVID on human fertility have been reported and include cases with premature ovarian failure and oligomenorrhoea in women and erectile dysfunction in men. Despite the increasing knowledge about the effects of COVID-19 infections on human gonads and fertility, the long-term consequences of the COVID-19 pandemic cannot yet be assessed in this context.
    Type of Medium: Online Resource
    ISSN: 0018-5043 , 1439-4286
    URL: Article
    DOI: 10.1055/a-1891-6621
    RVK:
    XA 46918
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2022
    detail.hit.zdb_id: 2056576-8
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