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  1. Artikel: JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome.

    Hargarten, Jessica C / Ssebambulidde, Kenneth / Anjum, Seher H / Vaughan, Malcolm J / Xu, Jintao / Song, Brian / Ganguly, Anutosh / Park, Yoon-Dong / Scott, Terri / Hammoud, Dima A / Olszewski, Michal A / Williamson, Peter R

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome ( ... ...

    Abstract Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull's rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44
    Sprache Englisch
    Erscheinungsdatum 2024-01-21
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.01.18.24301483
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Farnesol remodels the peritoneal cavity immune environment influencing

    Hargarten, Jessica C / Vaughan, Malcolm J / Lampe, Anna T / Jones, Riley M / Ssebambulidde, Kenneth / Nickerson, Kenneth W / Williamson, Peter R / Atkin, Audrey L / Brown, Deborah M

    Infection and immunity

    2023  Band 91, Heft 12, Seite(n) e0038423

    Abstract: ... Candida ... ...

    Abstract Candida albi
    Mesh-Begriff(e) Humans ; Animals ; Mice ; Candida albicans ; Farnesol/pharmacology ; Peritoneal Cavity/pathology ; Candidiasis/microbiology ; Intraabdominal Infections ; Virulence Factors
    Chemische Substanzen Farnesol (4602-84-0) ; Virulence Factors
    Sprache Englisch
    Erscheinungsdatum 2023-11-17
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00384-23
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Tocilizumab as a Potential Adjunctive Therapy to Corticosteroids in Cryptococcal Post-infectious Inflammatory Response Syndrome (PIIRS): a Report of Two Cases.

    Hargarten, Jessica C / Anjum, Seher H / Ssebambulidde, Kenneth / Park, Yoon-Dong / Vaughan, Malcolm J / Scott, Terri L / Hammoud, Dima A / Billioux, Bridgette Jeanne / Williamson, Peter R

    Journal of clinical immunology

    2023  Band 43, Heft 8, Seite(n) 2146–2155

    Abstract: Purpose: Non-HIV cryptococcal meningoencephalitis (CM) in previously healthy individuals is often complicated by a post-infectious inflammatory response syndrome (c-PIIRS) characterized by neurologic deterioration after appropriate antifungal therapy ... ...

    Abstract Purpose: Non-HIV cryptococcal meningoencephalitis (CM) in previously healthy individuals is often complicated by a post-infectious inflammatory response syndrome (c-PIIRS) characterized by neurologic deterioration after appropriate antifungal therapy with sterilization of CSF fungal cultures. c-PIIRS results from an excessive inflammatory response to fungal antigens released during fungal lysis, mediated by IFN-γ, IL-6, and activated T-helper cells, leading to immune-mediated host damage that responds to pulse-corticosteroid taper therapy (PCT). Typically, oral steroids may take up to a year to taper, and occasionally, patients will be refractory to steroid therapy or may demonstrate high-risk lesions such as those involving intracranial arteries. Also, patients can have problematic side effects from prolonged corticosteroids. Hence, appropriate adjunctive agents are needed to reduce corticosteroid doses in the treatment of c-PIIRS. Due to a possible role of IL-6 in pathogenesis, IL-6 receptor blockade by tocilizumab may be useful in the treatment of c-PIIRS.
    Methods: Two previously healthy patients with non-HIV cPIIRS were seen at the NIH. Due to concerns for intracranial vascular rupture in an area of inflammation (Patient 1) and intractable symptoms on high-dose oral corticosteroids (Patient 2) with evidence of persistent CSF inflammation, patients were treated with 4-8 mg/kg tocilizumab every 2 weeks while maintained on a constant dose of prednisone.
    Results: Two patients exhibited rapid immunological improvement following treatment with tocilizumab. Patient 1 remained vascularly stable, and Patient 2 had near resolution of headaches with improvement in mental status as evidenced by improved MOCA score. The two had improved CSF inflammatory parameters and no significant side effects. Both CSF cultures remained negative throughout treatment.
    Conclusions: Tocilizumab may be a safe adjunctive treatment for CM-related PIIRS suggesting further study.
    Mesh-Begriff(e) Humans ; Meningitis, Cryptococcal/diagnosis ; Meningitis, Cryptococcal/drug therapy ; Interleukin-6 ; Cryptococcus ; Inflammation ; Adrenal Cortex Hormones/therapeutic use ; Meningoencephalitis/drug therapy
    Chemische Substanzen tocilizumab (I031V2H011) ; Interleukin-6 ; Adrenal Cortex Hormones
    Sprache Englisch
    Erscheinungsdatum 2023-10-10
    Erscheinungsland Netherlands
    Dokumenttyp Case Reports ; Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-023-01592-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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