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  1. Article ; Online: The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality

    Avi Gurion Kaye / Robert Siegel

    PeerJ, Vol 8, p e

    a systematic review

    2020  Volume 10322

    Abstract: Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such ... ...

    Abstract Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or “cytokine storm,” which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. Methodology PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479). Results Combined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376–0.547], p < 0.001). Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%. Conclusions Important caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.
    Keywords COVID-19 ; Tocilizumab ; IL-6 ; SARS-COV-2 ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review.

    Kaye, Avi Gurion / Siegel, Robert

    PeerJ

    2020  Volume 8, Page(s) e10322

    Abstract: Background: In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such ... ...

    Abstract Background: In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or "cytokine storm," which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality.
    Methodology: PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479).
    Results: Combined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376-0.547],
    Conclusions: Important caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.
    Keywords covid19
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.10322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review

    Avi Gurion, Kaye Siegel Robert

    PeerJ

    Abstract: Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19 Evaluating the efficacy existing drugs may expedite the development of such therapeutics ...

    Abstract Background In the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19 Evaluating the efficacy existing drugs may expedite the development of such therapeutics Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or “cytokine storm,” which is largely mediated by the cytokine interleukin-6 (IL-6) The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality Methodology PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19 Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis The systematic analysis was pre-approved through PROSPERO (CRD42020193479) Results Combined mortality for the TCZ-treated and SOC groups were 26 0% and 43 4% respectively In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC A combined random effects odds ratio calculation yielded an odds ratio of 0 453 (95% CI [0 376–0 547], p < 0 001) Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16 0% Conclusions Important caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #902928
    Database COVID19

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  4. Article ; Online: The Efficacy of IL-6 Inhibitor Tocilizumab in Reducing Severe COVID-19 Mortality: A Systematic Review

    Kaye, Avi Gurion / Siegel, Robert

    medRxiv

    Abstract: Without proven, targeted therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19, potentially utilizing existing drugs. Severe COVID-19 is largely the result of a dysregulated immune response ... ...

    Abstract Without proven, targeted therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19, potentially utilizing existing drugs. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, also called a cytokine storm. The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress effects of the pro-inflammatory cytokine which drives the cytokine storm and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. 9 case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for a qualitative synthesis. In all of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ versus the SOC and a combined random effects odds ratio calculation yielded an odds ratio of 0.482 (p<0.001, 95% CI 0.326-0.713). Additionally, 12 uncontrolled trials were identified for a qualitative analysis producing a raw combined mortality rate of 13.6%. Results from the systematic analysis provide positive evidence for the potential efficacy of TCZ, validating the merit and need for ongoing clinical trials of the drug to treat severe COVID-19.
    Keywords covid19
    Language English
    Publishing date 2020-07-14
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.07.10.20150938
    Database COVID19

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  5. Article ; Online: Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver.

    Sarkar, Abby / Jin, Yinhua / DeFelice, Brian C / Logan, Catriona Y / Yang, Yan / Anbarchian, Teni / Wu, Peng / Morri, Maurizio / Neff, Norma F / Nguyen, Huy / Rulifson, Eric / Fish, Matthew / Kaye, Avi Gurion / Martínez Jaimes, Azalia M / Nusse, Roel

    eLife

    2023  Volume 12

    Abstract: Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to ... ...

    Abstract Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured.
    MeSH term(s) Mice ; Animals ; Liver Regeneration ; Intermittent Fasting ; Liver ; Fasting ; Hepatocytes ; Cell Proliferation
    Language English
    Publishing date 2023-01-31
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.82311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver

    Abby Sarkar / Yinhua Jin / Brian C DeFelice / Catriona Y Logan / Yan Yang / Teni Anbarchian / Peng Wu / Maurizio Morri / Norma F Neff / Huy Nguyen / Eric Rulifson / Matthew Fish / Avi Gurion Kaye / Azalia M Martínez Jaimes / Roel Nusse

    eLife, Vol

    2023  Volume 12

    Abstract: Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to ... ...

    Abstract Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured.
    Keywords liver ; regeneration ; intermittent fasting ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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