Browsing by Subject "Severity of illness index"

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    Severe Alcohol-Associated Hepatitis Is Associated With Worse Survival in Critically Ill Patients With Acute on Chronic Liver Failure
    (Wolters Kluwer, 2022) Patidar, Kavish R.; Peng, Jennifer L.; Kaur, Harleen; Worden, Astin; Kettler, Carla D.; Pike, Francis; Buckley, Caitriona A.; Orman, Eric S.; Desai, Archita P.; Nephew, Lauren D.; Kubal, Chandrashekhar A.; Gawrieh, Samer; Chalasani, Naga; Ghabril, Marwan S.; Medicine, School of Medicine
    Differences in mortality between critically ill patients with severe alcohol-associated hepatitis (sAH) and acute-on-chronic liver failure (ACLF) and non-sAH ACLF (i.e., ACLF not precipitated by sAH) are unknown. Such differences are important, as they may inform on prognosis and optimal timing of liver transplantation (LT). Thus, we aimed to compare short-term and longer-term mortality between patients with sAH ACLF and patients with non-sAH ACLF who were admitted to the intensive care unit. Patients with ACLF admitted from 2016-2018 at two tertiary care intensive care units were analyzed. SAH was defined by the National Institute on Alcohol Abuse and Alcoholism's Alcoholic Hepatitis Consortium and Model for End-Stage Liver Disease score >20. Mortality without LT was compared between sAH ACLF and non-sAH ACLF using Fine and Gray's competing-risks regression. A total of 463 patients with ACLF (18% sAH and 82% non-sAH) were included. Compared to patients with non-sAH ACLF, patients with sAH ACLF were younger (49 vs. 56 years; P < 0.001) and had higher admission Model for End-Stage Liver Disease (MELD) (35 vs. 25; P < 0.001) and Chronic Liver Failure Consortium (CLIF-C) scores (61 vs. 57; P = 0.002). There were no significant differences between the two groups for vasopressor, mechanical ventilation, and hemodialysis use. The cumulative incidence of death was significantly higher in patients with sAH ACLF compared to patients with non-sAH ACLF: 30-day 74.7% versus 45.3%; 90-day 81.9% versus 57.4%; 180-day 83.2% versus 63.0% (unadjusted subdistribution hazard ratio [sHR] 1.88 [95% confidence interval (CI) 1.44-2.46]; P < 0.001). After adjusting for CLIF-C score and infection in a multivariable competing-risk model, patients with sAH ACLF had significantly higher risk of death (sHR 1.57 [95% CI 1.20-2.06]; P = 0.001) compared to patients with non-sAH ACLF. Conclusion: Critically ill patients with sAH ACLF have worse mortality compared to patients with non-sAH ACLF. These data may inform prognosis in patients with sAH and ACLF, and early LT referral in potentially eligible patients.
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    Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)
    (Wiley, 2021) Wollenberg, A.; Blauvelt, A.; Guttman-Yassky, E.; Worm, M.; Lynde, C.; Lacour, J.-P.; Spelman, L.; Katoh, N.; Saeki, H.; Poulin, Y.; Lesiak, A.; Kircik, L.; Cho, S. H.; Herranz, P.; Cork, M. J.; Peris, K.; Steffensen, L. A.; Bang, B.; Kuznetsova, A.; Jensen, T. N.; Østerdal, M. L.; Simpson, E. L.; ECZTRA 1 and ECZTRA 2 study investigators; Dermatology, School of Medicine
    Background: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.
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    Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis
    (Wolters Kluwer, 2022) Yang, Zhihong; Han, Sen; Zhang, Ting; Kusumanchi, Praveen; Huda, Nazmul; Tyler, Kelsey; Chandler, Kristina; Skill, Nicholas J.; Tu, Wanzhu; Shan, Mu; Jiang, Yanchao; Maiers, Jessica L.; Perez, Kristina; Ma, Jing; Liangpunsakul, Suthat; Medicine, School of Medicine
    Alcohol-associated liver disease is the leading cause of chronic liver disease. We hypothesized that the expression of specific coding genes is critical for the progression of alcoholic cirrhosis (AC) from compensated to decompensated states. For the discovery phase, we performed RNA sequencing analysis of 16 peripheral blood RNA samples, 4 healthy controls (HCs) and 12 patients with AC. The DEGs from the discovery cohort were validated by quantitative polymerase chain reaction in a separate cohort of 17 HCs and 48 patients with AC (17 Child-Pugh A, 16 Child-Pugh B, and 15 Child-Pugh C). We observed that the numbers of differentially expressed messenger RNAs (mRNAs) were more pronounced with worsening disease severity. Pathway analysis for differentially expressed genes for patients with Child-Pugh A demonstrated genes involved innate immune responses; those in Child-Pugh B belonged to genes related to oxidation and alternative splicing; those in Child-Pugh C related to methylation, acetylation, and alternative splicing. We found significant differences in the expression of heme oxygenase 1 (HMOX1) and ribonucleoprotein, PTB binding 1 (RAVER1) in peripheral blood of those who died during the follow-up when compared to those who survived. Conclusion: Unique mRNAs that may implicate disease progression in patients with AC were identified by using a transcriptomic approach. Future studies to confirm our results are needed, and comprehensive mechanistic studies on the implications of these genes in AC pathogenesis and progression should be further explored.