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1.

001-es BibID:BIBFORM082949
Első szerző:Saha, Banishree
Cím:Biomarkers of Macrophage Activation and Immune Danger Signals Predict Clinical Outcomes in Alcoholic Hepatitis / Banishree Saha, David Tornai, Karen Kodys, Adeyinka Adejumo, Patrick Lowe, Craig McClain, Mack Mitchell, Arthur McCullough, Srinivasan Dasarathy, Aimee Kroll-Desrosiers, Bruce Barton, Svetlana Radaeva, Gyongyi Szabo
Dátum:2019
ISSN:0270-9139
Megjegyzések:Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients in four US academic medical centers. Plasma from AH patients had a significant increase in gut microbial translocation indicators (endotoxin, bacterial 16S ribosomal DNA) and host response indicators (soluble cluster of differentiation 14 [sCD14] and lipopolysaccharide binding protein [LBP]) compared to controls. Patient MELD score and Glasgow Alcoholic Hepatitis score (GAHS) correlated with endotoxin levels. AH patients also had a significant increase in high mobility group protein 1 (HMGB1), a sterile danger signal molecule, and osteopontin (OPN), a multifunctional phosphoprotein involved in neutrophil activation, compared to controls. Increased levels of OPN positively correlated with increasing MELD score, GAHS, and LBP levels. Consistent with these results, AH patients had significantly increased circulating levels of macrophage activation (sCD163 and sCD206) markers compared to healthy controls, and sCD163 and sCD206 significantly and positively correlated with OPN, HMGB1, and LBP levels as well as with MELD score and GAHS. These findings indicate a connection between microbial translocation, immune cell activation, and AH severity. Plasma sCD14, OPN, sCD163, and sCD206 levels were significantly higher in nonsurvivors than survivors. In multivariate regression models, we identified sCD14, sCD163, and OPN as independent predictors of 90-day mortality, infection, and organ failure development, respectively. Conclusion: Our study suggests that sCD14, LBP, OPN, sCD163, and sCD206 are biomarkers to indicate severity and predict clinical outcomes in AH.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
osteopontin
sCD206
sCD163
LBP
HMGB1
sCD14
organ failure
infection
Megjelenés:Hepatology. - 70 : 4 (2019), p. 1134-1149. -
További szerzők:Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Kodys, Karen Adejumo, Adeyinka Lowe, Patrick McClain, Craig Mitchell, Mack McCullough, Arthur Dasarathy, Srinivasan Kroll-Desrosiers, Aimee Barton, Bruce Radaeva, Svetlana Szabó Gyöngyi
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2.

001-es BibID:BIBFORM102659
035-os BibID:(Scopus)85134156844 (WOS)000826112000001
Első szerző:Szabó Gyöngyi
Cím:Response from Authors of HEP-21-2131.R1 / Gyongyi Szabo, Mack Mitchell, Craig J. McClain, Srinivasan Dasarathy, Bruce Barton, Arthur J. McCullough, Laura E. Nagy, Aimee Kroll-Desrosiers, David Tornai, Hyesung Alice Min, Svetlana Radaeva, Lisa Casey, Jennifer Cuthbert
Dátum:2022
ISSN:0270-9139
Tárgyszavak:Orvostudományok Klinikai orvostudományok hozzászólás
folyóiratcikk
Megjelenés:Hepatology. - 76 : 5 (2022), p. E114-E115. -
További szerzők:Mitchell, Mack McClain, Craig Dasarathy, Srinivasan Barton, Bruce McCullough, Arthur Nagy Laura E. Kroll-Desrosiers, Aimee Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Min, Hyesung Alice Radaeva, Svetlana Casey, Lisa Cuthbert, Jennifer
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3.

001-es BibID:BIBFORM101156
035-os BibID:(Scopus)85128889535 (WOS)000804710000001
Első szerző:Szabó Gyöngyi
Cím:IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis / Gyöngyi Szabó, Mack Mitchell, Craig J. McClain, Srinivasan Dasarathy, Bruce Barton, Arthur McCullough, Laura E. Nagy, Aimee Kroll-Desrosiers, David Tornai, Hyesung Alice Min, Svetlana Radaeva, M. E. Blair Holbein, Lisa Casey, Jennifer Cuthbert
Dátum:2022
ISSN:0270-9139
Megjegyzések:Background & aims: Patients with severe alcohol-associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180-day survival. Approach & results: Subjects with a clinical diagnosis of severe AH (MELD>20, MDF>32) were randomized to receive methylprednisolone (28 days) (PRED) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (180 days) (COMB). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014 and completed in March 2018. Five hundred (500) patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a Model for End Stage Liver Disease (MELD) score > 20. Fifty-three (53) patients were randomized into the COMB and fifty (50) to the PRED treatment; one dropped out of the study before randomization. The mean age was 45.3?10.4 years. 60.6% were males, 92.3% white, mean MELD 25.7?3.9. Kaplan-Meier survival estimate at 180-day was 67.9% in COMB and 56% in PRED (HR=0.69; p=0.3001). Survival curves separated by 90 days (COMB: 69.8%; PRED: 58.0%; HR=0.69, p=0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%) (HR=0.91, p=0.85). There were no unexpected serious adverse events and the incidence of infection was comparable between groups. MELD 20-25 and MELD >26 strata showed non-significant treatment effects in favor of COMB. Conclusions: A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Interleukin-1 antagonist
MELD
inflammation
interleukin-1
liver failure
Megjelenés:Hepatology. - 76 : 4 (2022), p. 1058-1068. -
További szerzők:Mitchell, Mack McClain, Craig Dasarathy, Srinivasan Barton, Bruce McCullough, Arthur Nagy Laura E. Kroll-Desrosiers, Aimee Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Min, Hyesung Alice Radaeva, Svetlana Holbein, M. E. Blair Casey, Lisa Cuthbert, Jennifer
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4.

001-es BibID:BIBFORM136235
Első szerző:Tornai Dávid (hepatológia, biomarker kutatás)
Cím:Longitudinal assessment of circulating cytokine profile of severe alcohol-associated hepatitis / Tornai David, Mitchell Mack C., McClain Craig J., Dasarathy Srinivasan, Barton Bruce, Szabo Gyongyi
Dátum:2026
ISSN:0270-9139
Megjegyzések:Background: Increased circulating pro-inflammatory cytokine levels correlate with mortality in severe alcohol-associated hepatitis (AH), but their kinetics during disease progression or response to treatment remain unexplored. Objective: We longitudinally assessed circulating biomarkers in a severe AH cohort enrolled in a multicenter, double-blind clinical trial. Design: Eighty-nine patients with severe AH (MELD?20) from 4 US sites were randomly assigned to treatment with IL-1receptor antagonist (IL-1Ra) + pentoxifylline + zinc (anakinra: 47) or methylprednisolone + placebo (steroid: 42). Plasma levels of 43 indicators of AH pathology (inflammation, bacterial translocation, liver regeneration, tissue remodeling, and cell-activation) were assessed on days 0, 7, 28, 90 and 180 after enrollment, and in 27 healthy controls. Results: Baseline characteristics and cytokine levels were similar between treatment groups but significantly different compared to healthy controls. Consistent with anakinra administration, day 7 IL-1Ra levels were significantly increased in the anakinra group accompanied by elevated levels of several other cytokines. IL-1? levels were increased in the steroid group on day 28. Strong correlations were observed between IL-1? and IL-17A as well as IL-1? and IL-13 both prior to and during treatment. Although the dysregulated biomarkers demonstrated improving trends in survivors, most did not normalize by day 180. Markers associated with 90-day mortality were distinct between the treatment groups with few exceptions (IL-13?absolute level; Sonic hedgehog and sTNFR-1?level change). Conclusions: Circulating cytokine and immune biomarkers dynamically change in AH during treatment, disease progression and/or resolution. Our results highlight the importance of treatment-specific biomarkers in future clinical trials.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
anakinra
steroid
Defeat Alcoholic SteatoHepatitis (DASH)
cytokine profile
interleukin
short-term mortality
Megjelenés:Hepatology. - [Epub ahead of print] (2026). -
További szerzők:Mitchell, Mack C. McClain, Craig Dasarathy, Srinivasan Barton, Bruce Szabó Gyöngyi
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5.

001-es BibID:BIBFORM115266
035-os BibID:(Scopus)85188172608 (WoS)001106244400001
Első szerző:Tornai Dávid (hepatológia, biomarker kutatás)
Cím:A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis : a multicenter plasma biomarker analysis / David Tornai, Mack Mitchell, Craig J. McClain, Srinivasan Dasarathy, Arthur McCullough, Svetlana Radaeva, Aimee Kroll-Desrosiers, JungAe Lee, Bruce Barton, Gyongyi Szabo
Dátum:2023
ISSN:2471-254X
Megjegyzések:Background: Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The Model for End-Stage Liver Disease (MELD) assesses disease severity and mortality, however, it is not specific for AH. We screened plasma samples from severe AH patients for biomarkers of multiple pathological processes and identified predictors of short-term mortality. Methods: Plasma was collected at baseline from 85 severe AH patients (MELD?20, MDF?32) enrolled in the DASH clinical trial (investigating IL-1receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers' association with 28 and 90-day mortality was assessed. Results: Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed association with mortality. Interleukin-6, IL-22, IFN-?2, sTNF-R1, lipocalin-2 and ?-fetoprotein levels were associated with 28-day, while IL-6, IL-13 and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2 and ?-fetoprotein levels were independent predictors of 28-day mortality and IL-6, IL-13, INR levels and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance predicting 90-day mortality compared to MELD in the total cohort and the individual treatment groups. Conclusions: We identified predictors of short-term mortality in a cohort exclusively involving severe AH patients. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of treatment type with a performance superior to MELD in severe AH.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
anakinra
interleukin
short-term mortality
composite score
prognosis
Megjelenés:Hepatology Communications. - 7 : 12 (2023), p. 1-13. -
További szerzők:Mitchell, Mack McClain, Craig Dasarathy, Srinivasan McCullough, Arthur Radaeva, Svetlana Kroll-Desrosiers, Aimee Lee, JungAe Barton, Bruce Szabó Gyöngyi
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6.

001-es BibID:BIBFORM102219
Első szerző:Tornai Dávid (hepatológia, biomarker kutatás)
Cím:A novel composite score of biomarkers and age predicts mortality in severe alcoholic hepatitis patients / Tornai Dávid, Mack C. Mitchell, Craig J. McClain, Srinivasan Dasarathy, Arthur J. McCullough, Svetlana Radaeva, Aimee Kroll-Desrosiers, Bruce Barton, Szabó Gyöngyi
Dátum:2019
ISSN:0270-9139
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:Hepatology. - 70 : Suppl. 1 (2019), p. 835A. -
További szerzők:Mitchell, Mack C. McClain, Craig Dasarathy, Srinivasan McCullough, Arthur Radaeva, Svetlana Kroll-Desrosiers, Aimee Barton, Bruce Szabó Gyöngyi
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Intézményi repozitóriumban (DEA) tárolt változat
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