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  1. Article ; Online: Diversity of atopic dermatitis and selection of immune targets.

    Rothenberg-Lausell, Camille / Bar, Jonathan / Del Duca, Ester / Guttman-Yassky, Emma

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2023  Volume 132, Issue 2, Page(s) 177–186

    Abstract: Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy ... ...

    Abstract Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy remains difficult. This therapeutic challenge may be attributed to the complex pathogenesis of AD. Although the T
    MeSH term(s) Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/genetics ; Immunoglobulin E ; Th2 Cells ; Skin/pathology ; Cytokines/metabolism
    Chemical Substances Immunoglobulin E (37341-29-0) ; Cytokines
    Language English
    Publishing date 2023-11-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2023.11.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Biologic and Small Molecule Therapy for Treating Moderate to Severe Atopic Dermatitis: Mechanistic Considerations.

    Rothenberg-Lausell, Camille / Bar, Jonathan / Dahabreh, Dante / Renert-Yuval, Yael / Del Duca, Ester / Guttman-Yassky, Emma

    The Journal of allergy and clinical immunology

    2024  

    Abstract: Atopic dermatitis (AD) is a complex and heterogeneous skin disease where achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, ...

    Abstract Atopic dermatitis (AD) is a complex and heterogeneous skin disease where achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. While traditionally characterized as a Th2-driven disease, extensive research has recently revealed the involvement of Th1, Th17, and Th22 immune pathways, as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin (TSLP), and IL-33. This review will explore the mechanistic effect of treatments for AD, focusing on monoclonal antibodies and JAK inhibitors. It will describe how these treatments modulate immune pathways, and examine their impact on key inflammatory and barrier biomarkers.
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2024.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Age of onset defines two distinct profiles of atopic dermatitis in adults

    Facheris, Paola / Da Rosa, Joel Correa / Pagan, Angel D. / Angelov, Michael / Del Duca, Ester / Rabinowitz, Grace / Gómez‐Arias, Pedro Jesús / Rothenberg‐Lausell, Camille / Estrada, Yeriel D. / Bose, Swaroop / Chowdhury, Mashkura / Shemer, Avner / Pavel, Ana B. / Guttman‐Yassky, Emma

    Allergy. 2023 Aug., v. 78, no. 8, p. 2202-2214

    2023  , Page(s) 2202–2214

    Abstract: BACKGROUND: The incidence of adult‐onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric‐onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted‐ ... ...

    Abstract BACKGROUND: The incidence of adult‐onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric‐onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted‐therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. METHODS: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT‐PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. RESULTS: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL‐36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p‐value < .05). In contrast, higher Th1‐(IFN‐γ, IL‐2, IL‐15, CCL5) upregulation and Th1‐skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro‐inflammatory and cardiovascular‐risk markers. Th1‐related products showed significant correlations between their skin and blood expressions only in AOAD subjects. CONCLUSION: Age‐of‐onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.
    Keywords RNA ; adulthood ; adults ; atopic dermatitis ; blood serum ; cell adhesion ; hyperplasia ; immunohistochemistry ; inflammation ; interleukin-15 ; interleukin-2 ; proteomics ; therapeutics
    Language English
    Dates of publication 2023-08
    Size p. 2202-2214
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15741
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis.

    Guttman-Yassky, Emma / Facheris, Paola / Da Rosa, Joel Correa / Rothenberg-Lausell, Camille / Del Duca, Ester / David, Eden / Estrada, Yeriel / Liu, Ying / Bose, Swaroop / Chowdhury, Mashkura / Munera, Catherine / Goncalves, Joana / Nograles, Kristine / Kim, Brian S / Lebwohl, Mark

    The Journal of allergy and clinical immunology

    2023  Volume 152, Issue 4, Page(s) 916–926

    Abstract: Background: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease.: Objective: We sought to evaluate the impact of the ... ...

    Abstract Background: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease.
    Objective: We sought to evaluate the impact of the selective κ-opioid receptor agonist difelikefalin (DFK) on pruritus intensity and pruritus- and immune-related biomarkers in subjects with moderate to severe AD-related pruritus.
    Methods: A phase 2 clinical trial investigated the efficacy and safety of oral DFK 0.25, 0.5, and 1.0 mg in subjects with moderate to severe AD-related pruritus. A biomarker substudy evaluated the effects of DFK on the expression of pruritus, T
    Results: In the clinical trial (N = 401), all DFK doses reduced itch versus placebo; however, the results were not statistically significant at week 12. In a subgroup of subjects in the trial with mild to moderate skin inflammation and moderate to severe itch (itch-dominant AD phenotype), DFK reduced itch at week 12 versus placebo. In the biomarker substudy, DFK downregulated the expression of key pruritus-related genes (eg, IL-31 and TRPV1) and the AD phenotype (eg, CCL17). Gene set variation analysis confirmed that DFK, but not placebo, downregulated pruritus-related genes and T
    Conclusions: DFK treatment reduced itch in subjects with moderate to severe AD-related pruritus, particularly those with an "itch-dominant" AD phenotype, and had an impact on the expression of pruritus, T
    MeSH term(s) Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/metabolism ; Pruritus/drug therapy ; Pruritus/metabolism ; Skin/metabolism ; Biomarkers/metabolism ; Severity of Illness Index
    Chemical Substances difelikefalin (NA1U919MRO) ; Biomarkers
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2023.06.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Do Atopic Dermatitis Patient-Reported Outcomes Correlate With Validated Investigator Global Assessment? Insights From TARGET-AD Registry.

    Guttman-Yassky, Emma / Bar, Jonathan / Rothenberg-Lausell, Camille / Eichenfield, Lawrence / Grada, Ayman / Abuabara, Katrina / Chapman, M / Calimlim, Brian / Wegzyn, Colleen / Gamelli, Amy / Krueger, Whitney / Munoz, Breda / Knapp, Keith / Faller, Rachel / Crawford, Julie / Silverberg, Jonathan

    Journal of drugs in dermatology : JDD

    2023  Volume 22, Issue 4, Page(s) 344–354

    Abstract: Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient- ...

    Abstract Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL).
    Methods: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children’s) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models.
    Results: The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD.
    Conclusions: In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.
    MeSH term(s) Adult ; Female ; Adolescent ; Humans ; Child ; Dermatitis, Atopic/diagnosis ; Quality of Life ; Cross-Sectional Studies ; Surveys and Questionnaires ; Severity of Illness Index ; Patient Reported Outcome Measures ; Registries
    Language English
    Publishing date 2023-04-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2145090-0
    ISSN 1545-9616
    ISSN 1545-9616
    DOI 10.36849/JDD.7473
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Age of onset defines two distinct profiles of atopic dermatitis in adults.

    Facheris, Paola / Da Rosa, Joel Correa / Pagan, Angel D / Angelov, Michael / Del Duca, Ester / Rabinowitz, Grace / Gómez-Arias, Pedro Jesús / Rothenberg-Lausell, Camille / Estrada, Yeriel D / Bose, Swaroop / Chowdhury, Mashkura / Shemer, Avner / Pavel, Ana B / Guttman-Yassky, Emma

    Allergy

    2023  Volume 78, Issue 8, Page(s) 2202–2214

    Abstract: Background: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted- ... ...

    Abstract Background: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD.
    Methods: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile.
    Results: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects.
    Conclusion: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.
    MeSH term(s) Child ; Adult ; Humans ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/epidemiology ; Dermatitis, Atopic/genetics ; Age of Onset ; Proteomics ; Skin/pathology ; Inflammation/pathology
    Language English
    Publishing date 2023-04-18
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 125: Show issues

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