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  1. Article ; Online: Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

    Lu, Mei / Salgia, Reena / Li, Jia / Trudeau, Sheri / Rupp, Loralee B / Wu, Trueman / Daida, Yihe G / Schmidt, Mark A / Gordon, Stuart C

    Journal of viral hepatitis

    2023  Volume 30, Issue 9, Page(s) 746–755

    Abstract: Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from ...

    Abstract Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.
    MeSH term(s) Humans ; Male ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/prevention & control ; Antiviral Agents/therapeutic use ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Liver Neoplasms/etiology ; Liver Neoplasms/complications ; Cohort Studies ; Risk Assessment ; Sustained Virologic Response ; Liver Cirrhosis/complications ; Hepatitis C/drug therapy
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2023-07-06
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 1212497-7
    ISSN 1365-2893 ; 1352-0504
    ISSN (online) 1365-2893
    ISSN 1352-0504
    DOI 10.1111/jvh.13859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4119: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article: Early therapeutic effects of an Angiopoietin-1 mimetic peptide in middle-aged rats with vascular dementia.

    Gao, Huanjia / Findeis, Elizabeth L / Culmone, Lauren / Powell, Brianna / Landschoot-Ward, Julie / Zacharek, Alex / Wu, Trueman / Lu, Mei / Chopp, Michael / Venkat, Poornima

    Frontiers in aging neuroscience

    2023  Volume 15, Page(s) 1180913

    Abstract: Background: Vascular Dementia (VaD) refers to dementia caused by cerebrovascular disease and/or reduced blood flow to the brain and is the second most common form of dementia after Alzheimer's disease. We previously found that in middle-aged rats ... ...

    Abstract Background: Vascular Dementia (VaD) refers to dementia caused by cerebrovascular disease and/or reduced blood flow to the brain and is the second most common form of dementia after Alzheimer's disease. We previously found that in middle-aged rats subjected to a multiple microinfarction (MMI) model of VaD, treatment with AV-001, a Tie2 receptor agonist, significantly improves short-term memory, long-term memory, as well as improves preference for social novelty compared to control MMI rats. In this study, we tested the early therapeutic effects of AV-001 on inflammation and glymphatic function in rats subjected to VaD.
    Methods: Male, middle-aged Wistar rats (10-12 m), subjected to MMI, were randomly assigned to MMI and MMI + AV-001 treatment groups. A sham group was included as reference group. MMI was induced by injecting 800 ± 200, 70-100 μm sized, cholesterol crystals into the internal carotid artery. Animals were treated with AV-001 (1 μg/Kg, i.p.) once daily starting at 24 h after MMI. At 14 days after MMI, inflammatory factor expression was evaluated in cerebrospinal fluid (CSF) and brain. Immunostaining was used to evaluate white matter integrity, perivascular space (PVS) and perivascular Aquaporin-4 (AQP4) expression in the brain. An additional set of rats were prepared to test glymphatic function. At 14 days after MMI, 50 μL of 1% Tetramethylrhodamine (3 kD) and FITC conjugated dextran (500 kD) at 1:1 ratio were injected into the CSF. Rats (4-6/group/time point) were sacrificed at 30 min, 3 h, and 6 h from the start of tracer infusion, and brain coronal sections were imaged using a Laser scanning confocal microscope to evaluate tracer intensities in the brain.
    Result: Treatment of MMI with AV-001 significantly improves white matter integrity in the corpus callosum at 14 days after MMI. MMI induces significant dilation of the PVS, reduces AQP4 expression and impairs glymphatic function compared to Sham rats. AV-001 treatment significantly reduces PVS, increases perivascular AQP4 expression and improves glymphatic function compared to MMI rats. MMI significantly increases, while AV-001 significantly decreases the expression of inflammatory factors (tumor necrosis factor-α (TNF-α), chemokine ligand 9) and anti-angiogenic factors (endostatin, plasminogen activator inhibitor-1, P-selectin) in CSF. MMI significantly increases, while AV-001 significantly reduces brain tissue expression of endostatin, thrombin, TNF-α, PAI-1, CXCL9, and interleukin-6 (IL-6).
    Conclusion: AV-001 treatment of MMI significantly reduces PVS dilation and increases perivascular AQP4 expression which may contribute to improved glymphatic function compared to MMI rats. AV-001 treatment significantly reduces inflammatory factor expression in the CSF and brain which may contribute to AV-001 treatment induced improvement in white matter integrity and cognitive function.
    Language English
    Publishing date 2023-05-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2023.1180913
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antiviral Treatment and Response are Associated With Lower Risk of Dementia Among Hepatitis C Virus-Infected Patients.

    Tao, Meng-Hua / Gordon, Stuart C / Wu, Trueman / Trudeau, Sheri / Rupp, Loralee B / Gonzalez, Humberto C / Daida, Yihe G / Schmidt, Mark A / Lu, Mei

    The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

    2023  Volume 32, Issue 5, Page(s) 611–621

    Abstract: Objective: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic ... ...

    Abstract Objective: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV.
    Methods: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk.
    Results: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia.
    Conclusion: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients.
    MeSH term(s) Humans ; Antiviral Agents/adverse effects ; Hepacivirus ; Cohort Studies ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/epidemiology ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Liver Cirrhosis/complications ; Liver Cirrhosis/drug therapy ; Dementia/etiology ; Dementia/chemically induced
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2023-12-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 1278145-9
    ISSN 1545-7214 ; 1064-7481
    ISSN (online) 1545-7214
    ISSN 1064-7481
    DOI 10.1016/j.jagp.2023.12.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4443: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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