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  1. Article ; Online: The Role of Kynurenines Produced by Indolamine-2,3-Dioxygenase 1 in Sepsis.

    Lerch, Simon / Schefold, Joerg C / Spinetti, Thibaud

    Pharmacology

    2022  Volume 107, Issue 7-8, Page(s) 359–367

    Abstract: Background: The enzyme indolamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme of the kynurenine (KYN) pathway and metabolizes the essential amino acid tryptophan to KYNs. The depletion of tryptophan and the generation of KYNs were shown to be ... ...

    Abstract Background: The enzyme indolamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme of the kynurenine (KYN) pathway and metabolizes the essential amino acid tryptophan to KYNs. The depletion of tryptophan and the generation of KYNs were shown to be involved in the global downregulation of the immune system during the later stages of sepsis, also referred to as sepsis-associated immunosuppression.
    Summary: The generation of KYNs by IDO1 leads to a depletion of effector T cells, including increased rate of apoptosis, decreased ability of T-cell proliferation and activation, and the generation of FoxP3+ regulatory T cells. Furthermore, KYN was shown a potent vasorelaxant during inflammation-induced hypotension. Experimental studies in murine sepsis models and in humans show promising data for using the activation of IDO1 both as a prognostic marker and potential drug target in sepsis.
    MeSH term(s) Animals ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Kynurenine/metabolism ; Mice ; Sepsis/drug therapy ; Sepsis/metabolism ; T-Lymphocytes, Regulatory/metabolism ; Tryptophan/metabolism
    Chemical Substances Indoleamine-Pyrrole 2,3,-Dioxygenase ; Kynurenine (343-65-7) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2022-04-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 206671-3
    ISSN 1423-0313 ; 0031-7012
    ISSN (online) 1423-0313
    ISSN 0031-7012
    DOI 10.1159/000523965
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immune biomarker-based enrichment in sepsis trials.

    Spinetti, Thibaud / Meisel, Christian / von Gunten, Stephan / Schefold, Joerg C

    Critical care (London, England)

    2020  Volume 24, Issue 1, Page(s) 58

    MeSH term(s) Biomarkers ; Humans ; Interleukin-8 ; Prognosis ; Prospective Studies ; Sepsis
    Chemical Substances Biomarkers ; Interleukin-8
    Keywords covid19
    Language English
    Publishing date 2020-02-19
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2051256-9
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-020-2774-1
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  3. Article ; Online: Adrenomedullin in COVID-19 induced endotheliitis.

    Wilson, Darius Cameron / Schefold, Joerg C / Baldirà, Jaume / Spinetti, Thibaud / Saeed, Kordo / Elke, Gunnar

    Critical care (London, England)

    2020  Volume 24, Issue 1, Page(s) 411

    MeSH term(s) Adrenomedullin/therapeutic use ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/physiopathology ; Endothelium/virology ; Humans ; Inflammation/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/physiopathology
    Chemical Substances Adrenomedullin (148498-78-6)
    Keywords covid19
    Language English
    Publishing date 2020-07-09
    Publishing country England
    Document type Letter
    ZDB-ID 2051256-9
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-020-03151-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Adrenomedullin in COVID-19 induced endotheliitis

    Darius Cameron Wilson / Joerg C. Schefold / Jaume Baldirà / Thibaud Spinetti / Kordo Saeed / Gunnar Elke

    Critical Care, Vol 24, Iss 1, Pp 1-

    2020  Volume 2

    Keywords Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9 ; covid19
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment - A narrative review.

    Pfortmueller, Carmen A / Spinetti, Thibaud / Urman, Richard D / Luedi, Markus M / Schefold, Joerg C

    Best practice & research. Clinical anaesthesiology

    2020  Volume 35, Issue 3, Page(s) 351–368

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus-19 disease (COVID-19) and is a major health concern. Following two SARS-CoV-2 pandemic "waves," intensive care unit (ICU) specialists are treating a large number of COVID19- ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus-19 disease (COVID-19) and is a major health concern. Following two SARS-CoV-2 pandemic "waves," intensive care unit (ICU) specialists are treating a large number of COVID19-associated acute respiratory distress syndrome (ARDS) patients. From a pathophysiological perspective, prominent mechanisms of COVID19-associated ARDS (CARDS) include severe pulmonary infiltration/edema and inflammation leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis, endothelial inflammation (endotheliitis), vascular thrombosis, and immune cell activation. Although the syndrome ARDS serves as an umbrella term, distinct, i.e., CARDS-specific pathomechanisms and comorbidities can be noted (e.g., virus-induced endotheliitis associated with thromboembolism) and some aspects of CARDS can be considered ARDS "atypical." Importantly, specific evidence-based medical interventions for CARDS (with the potential exception of corticosteroid use) are currently unavailable, limiting treatment efforts to mostly supportive ICU care. In this article, we will discuss the underlying pulmonary pathophysiology and the clinical management of CARDS. In addition, we will outline current and potential future treatment approaches.
    Language English
    Publishing date 2020-12-17
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2051316-1
    ISSN 1878-1608 ; 1753-3740 ; 1521-6896
    ISSN (online) 1878-1608
    ISSN 1753-3740 ; 1521-6896
    DOI 10.1016/j.bpa.2020.12.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Adrenomedullin in COVID-19 induced endotheliitis

    Wilson, Darius Cameron / Schefold, Joerg C. / Baldirà, Jaume / Spinetti, Thibaud / Saeed, Kordo / Elke, Gunnar

    Critical Care

    2020  Volume 24, Issue 1

    Keywords Critical Care and Intensive Care Medicine ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2041406-7
    ISSN 1364-8535
    ISSN 1364-8535
    DOI 10.1186/s13054-020-03151-7
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Adrenomedullin in COVID-19 induced endotheliitis.

    Wilson, Darius Cameron / Schefold, Joerg C. / Baldirà, Jaume / Spinetti, Thibaud / Saeed, Kordo / Elke, Gunnar

    Wilson, Darius Cameron; Schefold, Joerg C.; Baldirà, Jaume; Spinetti, Thibaud; Saeed, Kordo; Elke, Gunnar (2020). Adrenomedullin in COVID-19 induced endotheliitis. Critical care, 24(1), p. 411. BioMed Central 10.1186/s13054-020-03151-7

    2020  

    Keywords 610 Medicine & health ; covid19
    Language English
    Publishing date 2020-07-09
    Publisher BioMed Central
    Publishing country ch
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response.

    Hirzel, Cédric / Grandgirard, Denis / Surial, Bernard / Wider, Manon F / Leppert, David / Kuhle, Jens / Walti, Laura N / Schefold, Joerg C / Spinetti, Thibaud / Suter-Riniker, Franziska / Dijkman, Ronald / Leib, Stephen L

    Therapeutic advances in neurological disorders

    2022  Volume 15, Page(s) 17562864221080528

    Abstract: Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory ... ...

    Abstract Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated.
    Methods: In a prospective cohort study, we recruited patients with mild-moderate (
    Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies.
    Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.
    Language English
    Publishing date 2022-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2442245-9
    ISSN 1756-2864 ; 1756-2856
    ISSN (online) 1756-2864
    ISSN 1756-2856
    DOI 10.1177/17562864221080528
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  10. Article ; Online: Reduced Monocytic Human Leukocyte Antigen-DR Expression Indicates Immunosuppression in Critically Ill COVID-19 Patients.

    Spinetti, Thibaud / Hirzel, Cedric / Fux, Michaela / Walti, Laura N / Schober, Patrick / Stueber, Frank / Luedi, Markus M / Schefold, Joerg C

    Anesthesia and analgesia

    2020  Volume 131, Issue 4, Page(s) 993–999

    Abstract: Background: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human ... ...

    Abstract Background: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients.
    Methods: In a preliminary prospective monocentric observational study, 16 COVID-19-positive patients (75% male, median age: 68 [interquartile range 59-75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25-32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients.
    Results: While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19-induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118-42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission.
    Conclusions: When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.
    MeSH term(s) APACHE ; Aged ; Antibodies/analysis ; Antibodies/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Critical Care ; Critical Illness ; Down-Regulation/immunology ; Female ; HLA-DR Antigens/biosynthesis ; HLA-DR Antigens/immunology ; Humans ; Immune Tolerance/immunology ; Immunotherapy ; Lipopolysaccharide Receptors/immunology ; Male ; Middle Aged ; Monocytes/immunology ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Prospective Studies ; Respiratory Insufficiency/immunology ; Respiratory Insufficiency/physiopathology
    Chemical Substances Antibodies ; HLA-DR Antigens ; Lipopolysaccharide Receptors
    Keywords covid19
    Language English
    Publishing date 2020-12-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80032-6
    ISSN 1526-7598 ; 0003-2999
    ISSN (online) 1526-7598
    ISSN 0003-2999
    DOI 10.1213/ANE.0000000000005044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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