tbuckley/cabot-search huggingface dataset:
Dupilumab‐associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation
Authors: Kathrin Thormann, Anne‐Sophie Lüthi, Felix Deniau, Anja Heider, Simone Cazzaniga, Susanne Radonjic‐Hoesli, Mathias Lehmann, Christoph Schlapbach, Elio L. Herzog, Marco Kreuzer, Martin S. Zinkernagel, Cezmi A. Akdis, Denise C. Zysset‐Burri, Hans‐Uwe Simon, Dagmar Simon
Journal: Allergy (2024)

Abstract Background Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab‐associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non‐AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. Results Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL‐12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non‐AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. Conclusions DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD.
Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia
Authors: Elias Jabbour, Gerhard Zugmaier, Vaibhav Agrawal, Pilar Martínez‐Sánchez, José J. Rifón Roca, Ryan D. Cassaday, Boris Böll, Anita Rijneveld, Maher Abdul‐Hay, Françoise Huguet, Thomas Cluzeau, Mar Tormo Díaz, Vladan Vucinic, José González‐Campos, Alessandro Rambaldi, Stefan Schwartz, Céline Berthon, Jesús María Hernández‐Rivas, Paul R. Gordon, Monika Brüggemann, Ali Hamidi, Yuqi Chen, Hansen L. Wong, Bharat Panwar, Yuliya Katlinskaya, Ana Markovic, Hagop Kantarjian
Journal: American Journal of Hematology (2024)

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3
Boosting Checkpoint Immunotherapy with Biomimetic Nanodrug Delivery Systems
Authors: Wenjing Chen, Chenlu Tang, Guijin Chen, Jiale Li, Nengjin Li, Hanwen Zhang, Liuqing Di, Ruoning Wang
Journal: Advanced Healthcare Materials (2024)

Immune checkpoint blockade (ICB) has achieved unprecedented progress in tumor immunotherapy by blocking specific immune checkpoint molecules. However, the high biodistribution of the drug prevents it from specifically targeting tumor tissues, leading to immune-related adverse events. Biomimetic nanodrug delivery systems (BNDSs) readily applicable to ICB therapy have been widely developed at the preclinical stage to avoid immune-related adverse events. By exploiting or mimicking complex biological structures, the constructed BNDS as a novel drug delivery system has good biocompatibility and certain tumor-targeting properties. Herein, the latest findings regarding the aforementioned therapies associated with ICB therapy are highlighted. Simultaneously, prospective bioinspired engineering strategies can be designed to overcome the four-level barriers to drug entry into lesion sites. In future clinical translation, BNDS-based ICB combination therapy represents a promising avenue for cancer treatment.
Substituting Poly(ethylene glycol) Lipids with Poly(2‐ethyl‐2‐oxazoline) Lipids Improves Lipid Nanoparticle Repeat Dosing
Authors: Alejandro J. Da Silva Sanchez, David Loughrey, Elisa Schrader Echeverri, Sebastian G. Huayamares, Afsane Radmand, Kalina Paunovska, Marine Hatit, Karen E. Tiegreen, Philip J. Santangelo, James E. Dahlman
Journal: Advanced Healthcare Materials (2024)

Abstract Poly(ethylene glycol) (PEG)–lipids are used in Food‐and‐Drug‐Administration‐approved lipid nanoparticle (LNP)–RNA drugs, which are safe and effective. However, it is reported that PEG–lipids may also contribute to accelerated blood clearance and rare cases of hypersensitivity; this highlights the utility of exploring PEG–lipid alternatives. Here, it is shown that LNPs containing poly(2‐ethyl‐2‐oxazoline) (PEOZ)–lipids can deliver messenger RNA (mRNA) to multiple cell types in mice inside and outside the liver. In addition, it is reported that LNPs formulated with PEOZ–lipids show reduced clearance from the bloodstream and lower levels of antistealth lipid immunoglobulin Ms than LNPs formulated with PEG–lipids. These data justify further exploration of PEOZ–lipids as alternatives to PEG–lipids in LNP–RNA formulations.
Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy
Authors: Yuanwei Pan, Xianjia Wu, Lujie Liu, Chenchen Zhao, Jing Zhang, Shengren Yang, Pan Pan, Qinqin Huang, Xing‐Zhong Zhao, Rui Tian, Lang Rao
Journal: Advanced Healthcare Materials (2024)

Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co-stimulatory molecules limits their clinical applications. Here, a genetically engineered cancer cytomembrane nanovaccine is reported that simultaneously overexpresses co-stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulate dendritic cell (DC)-mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocks PD1/PD-L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefiting from the targeting ability of cancer cytomembranes, this nanovaccines formula shows an enhanced lymph node trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induces twofold DC maturation and shows satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporating cytomembrane components and co-stimulatory molecules for enhanced cancer immunotherapy.
550 - Vitiligo is associated with new onset osteoporosis: a population-based study
Authors: Naama Tova Cohen, Nanette B Silverberg, Khalaf Kridin
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Vitiligo, an autoimmune disease leading to skin depigmentation, affects about 2% of the global population. The current pathogenesis for vitiligo is the autoimmune theory; recent reports demonstrated the role of pro-inflammatory cytokines in vitiligo. Osteoporosis is an inflammatory condition, characterized by elevated pro-inflammatory cytokines, associated with increased bone metabolism. The association between osteoporosis and vitiligo has never been investigated in a cohort study. We aimed to investigate if patients with vitiligo are at increased risk for developing osteoporosis. Methods A retrospective, cohort study was conducted on the Clalit Health Services (CHS) database (2002-2019) exploring age, sex, ethnicity, comorbidities, and Charlson comorbidity index. Results 19,985 vitiligo patients, and 99,003 controls, mean age 33.2 (SD +/-21.6) years were included. The incidence rates (95%CI) of new-onset osteoporosis were 2.6 (2.3-2.9)/1,000 person-years (PY) in vitiligo patients and 2.2 (2.1-2.3)/1,000PY in the control group. In multivariate analysis adjusted for age, sex, ethnicity, smoking, obesity, hyperlipidemia, diabetes mellitus, and hypertension, the hazard ratio (95% CI) for new-onset osteoporosis in patients with vitiligo was 1.19 (1.04-1.38, p-value 0.006). In vitiligo patients, the odds ratio (95%CI) for osteoporosis were 2.05 (1.91-2.21, p-value &amp;lt;0.001), female sex 4.04 (3.03-5.38, p-value 0.001), Jewish ethnicity 3.65 (2.45-5.44, p-value &amp;lt;0.001), hypertension 5.02 (3.96-6.36, p-value &amp;lt;0.001), hyperlipidemia 6.99 (5.37-9.08, p-value &amp;lt;0.001), obesity 1.34 (1.02-1.76, p-value-0.036) and diabetes mellitus 3.56 (2.74-4.62, p-value &amp;lt;0.001). Conclusions In the current study we observed an increased risk of developing osteoporosis in patients with vitiligo. Our observation merits further study and highlights the systemic aspect of inflammation in vitiligo.
509 - Dupilumab improves disease severity in children less than 12 years of age with moderate-severe AD: interim results from PEDISTAD real-world registry
Authors: Eulalia Baselga, Michele Ramien, Danielle Marcoux, Marlies de Graaf, Alan D Irvine, Vania Oliveira Carvalho, Ledit R F Ardusso, Mirna Toledo-Bahena, Rajan Gupta, Thu Tong, Annie Zhang
Journal: British Journal of Dermatology (2024)

Abstract Introduction In phase 3 studies, dupilumab significantly improved disease severity in children with moderate-to-severe atopic dermatitis (AD). However, the impact of this systemic treatment on children in real-world treatment settings is yet to be investigated. Objectives To report the real-world effectiveness and safety of dupilumab in children the PEDISTAD registry. Methods PEDISTAD (NCT03687359) is an ongoing, international, longitudinal, observational 10-year registry study in patients aged from 6 months to 11 years at enrollment with moderate-to-severe AD, whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are medically inadvisable. This interim analysis measures the effect of dupilumab on Eczema Area and Severity Index (EASI) total score and %-affected body surface area (BSA) from therapy start to up to 3 years’ follow up. Safety was also evaluated. Results A total of 214 patients received dupilumab (median treatment observation period: 16.1 months; accumulated 3-year discontinuation rate: 13.3%). The proportion of patients with clear/mild AD (EASI score &amp;lt;7 [range 0–28]) increased from 20.8% at therapy start to 76.7% at last observation. The mean (±SE) EASI score decreased with dupilumab use, from 19.7±1.0 at therapy start to 6.1±0.8 at last observation. The proportion of patients with &amp;lt;10% BSA affected by AD increased from 12.6% at therapy start to 46.5% at last observation. The mean (± SE) BSA affected decreased from 38.3%±1.7 at therapy start to 17.1%±2.0 at last observation. 24.2% of patients had adverse events, including 2.4% serious adverse events. Conclusions Dupilumab treatment significantly improved disease severity in patients aged from 6 months to 11 years in real-world practice.
508 - Dupilumab treatment normalizes intraepidermal nerve fiber density in patients with moderate-to-severe AD
Authors: Sonja Ständer, Konstantin Agelopoulos, Leigh Nattkemper, Jerry Bagel, Amy Praestgaard, Gabriel Bologna, Madison Mack, Joseph Zahn, Annie Zhang, Gil Yosipovitch
Journal: British Journal of Dermatology (2024)

Abstract Introduction Chronic pruritus is a characteristic of atopic dermatitis (AD), contributing to poor quality of life in patients. Alterations in neuroanatomy and neuroarchitecture associated with pruritus secondary to AD are not fully understood. Objectives To explore the role of dupilumab treatment effect on epidermal neuroanatomy by quantifying intraepidermal nerve fiber density (IENFD). Method DIFFERENSTAD (NCT04823130) was an open-label, exploratory study that enrolled patients ≥ 18 years old with moderate-to-severe AD, pruritus lasting &amp;gt; 6 weeks, and Worst Itch Numerical Rating Scale (WI-NRS) ≥ 4, and matched healthy controls. Patients with AD received dupilumab 300 mg every 2 weeks for 16 weeks. Skin biopsies were obtained from patients’ lesional skin at baseline and localization-matched skin at Week 17 (end of treatment, EoT) and from healthy controls. The primary endpoint, IENFD, was defined as number of nerve fibers crossing the basement membrane per millimeter. Results 31 patients with moderate-to-severe AD and 10 matched controls were enrolled. IENFD in patients with AD significantly increased from baseline to EoT (mean [SE]: 7.7 [1.3] at baseline vs 12.1 [2.0] at EoT for patients with AD; P = 0.0017), to levels comparable with the control group (mean [SE]: 12.4 [2.3]; P for control group vs EoT in patients with AD = 0.9374). Mean (SE) Eczema Area and Severity Index (EASI) total score and WI-NRS in dupilumab-treated patients were 22.5 (1.5) and 8.5 (0.3) at baseline, and 5.1 (1.1) and 3.1 (0.5) at EoT (both change from baseline P &amp;lt; 0.0001), respectively. The safety profile was consistent with the known safety profile for dupilumab. Conclusions Dupilumab treatment significantly increased IENFD to levels similar to those of healthy subjects, suggesting restored neuroanatomy in patients with moderate-to-severe AD. Dupilumab also significantly improved clinical signs and pruritus symptoms of AD.
561 - Dupilumab treatment reduces signs in patients with atopic hand and foot dermatitis: results from a phase 3, randomized, double-blind, placebo-controlled trial
Authors: Eric L Simpson, Weily Soong, Margitta Worm, Andreas Pinter, Koji Masuda, Liyang Shao, Ariane Dubost-Brama, Ashish Bansal, Andrew Korotzer, Ana B Rossi
Journal: British Journal of Dermatology (2024)

Abstract Introduction/Background Dupilumab has previously shown overall efficacy in treating atopic hand and foot dermatitis. Objective To report the effect of dupilumab treatment on individual signs of atopic hand and foot dermatitis. Methods The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis presents the proportion of patients reporting absent, mild, moderate, or severe erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures, assessed by the modified total lesion sign score (mTLSS) in hands and feet. Results At baseline, most patients had scores of moderate or severe signs on their hands. Of the 133 patients enrolled, over 65% of patients treated with dupilumab (n = 67) achieved an absent or mild score by Week 16 in each of the signs/symptoms assessed. Proportion of patients with absent or mild hand scores increased from baseline to Week 16 in erythema (9% vs 71.6%), scaling/flaking (16.4% vs 74.7%), lichenification (4.5% vs 65.6%), vesiculation/erosion (43.3% vs 89.6%), edema (44.7% vs 86.6%), and fissures (23.9% vs 83.5%). Proportion of patients with absent or mild foot scores increased from baseline to Week 16 in erythema (56.7% vs 80.6%), scaling/flaking (56.7% vs 82.1%), lichenification (53.8% vs 82.1%), vesiculation/erosion (76.1% vs 86.6%), edema (76.1% vs 88.1%), and fissures (77.6% vs 86.6%). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions Dupilumab treatment in patients improves signs of hand and foot dermatitis, including erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures.
487 - Adult atopic dermatitis is associated with impaired oral health and oral dysbiosis - a case-control study
Authors: Aaya Shahin, Yael A Leshem, Yossi Taieb, Sharon Baum, Aviv Barzilai, Danielle Jedda, Efrat Sharon, Omry Koren, Shunit Coppenhagen-Glazer, Ronen Hazan, Yael Houri-Haddad, Shoshana Greenberger
Journal: British Journal of Dermatology (2024)

Abstract Background Previous studies linked chronic oral diseases to skin disorders such as psoriasis. However, data about oral health and oral microbiota in atopic dermatitis (AD) is sparse. Objectives To compare the oral health status and oral microbiota of AD patients and healthy controls. Methods This was a prospective sex and age- matched case-control study comparing adult participants with and without dermatologist-verified AD. Exclusion criteria included recent use of oral, topical, or systemic medication that could affect oral health or microbiome assessment. Oral health indices including Gingival Index, Plaque Index, Oral Hygiene Index, Caries Severity Index and prosthodontics status, were assessed by a dentist. Samples of oral flora were collected and subjected to high-throughput 16S rRNA gene sequencing analysis for microbiome analysis. Results Forty-five AD participants and 41 non-AD controls were recruited. The two groups had no significant differences in terms of their demographic and clinical characteristics, except for the higher rate of atopic co-morbidities in the AD group (p&amp;lt;.001). Compared to the control group, participants with AD had significantly poorer plaque (p=0.04) and oral hygiene indices (p=0.04) and a trend towards higher gingival index (p=0.05). The results of the Faith phylogenetic diversity (FDR) test indicated that the oral microbial diversity in the AD group was significantly higher (α-diversity, FDR-adjusted p=0.0007) when compared with the control group. Characterization of the similarities and differences in the composition of the microbial communities between the samples (β-diversity) from the AD patients and controls indicated that they clustered separately. The groups showed significant dissimilarity and distinct clustering of microbial abundance (FDR-adjusted p=0.001). Importantly, higher community diversity was previously linked to periodontitis and gingival disease. Furthermore, AD patients had a significantly increased abundance of taxa correlated with oral diseases and decreased abundance of oral health-associated bacteria. Conclusion AD appears to be associated with poorer oral health and oral dysbiosis, and thus, there is a need to increase the awareness of both patients and physicians about oral health.
543 - Early repigmentation of stable vitiligo through point-of-care melanocyte transfer using non-cultured autologous skin cell suspension
Authors: Munavalli Girish
Journal: British Journal of Dermatology (2024)

Abstract Introduction Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1–3 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).4 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. Objective The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.
482 - Efficacy and safety of sequential topical 0.1% mometasone furoate cream and 2% crisaborole in the treatment of mild to moderate atopic dermatitis in children aged over 2 years—a multicentre parallel randomised controlled study in China
Authors: Huan Yang, Hong Shu, Limin Miao, Ping Li, Shan Wang, Hua Qian, Zhenping Chen, Xiaoyan Luo, Lin Ma, Hua Wang
Journal: British Journal of Dermatology (2024)

Abstract Background Atopic dermatitis (AD) is a chronic, recurrent pruritic, inflammatory skin disease associated with genetic allergies. Crisaborole is a phosphodiesterase 4 (PDE4) inhibitor approved by the US Food and Drug Administration for the treatment of patients over 2 years of age with mild to moderate AD. Previous studies have focused on the efficacy of crisaborole in the treatment of AD, and its influence on AD recurrence is not clear. Objective To explore the efficacy and safety of sequential topical 0.1% mometasone furoate cream (Elosone) and crisaborole in the treatment of mild to moderate AD in children, and to investigate the effect of crisaborole on the recurrence of AD. Methods Results Conclusion Treatment of mild to moderate AD in children over 2 years of age with sequential topical 0.1% mometasone furoate and crisaborole significantly reduced relapses and the amount of mometasone furoate prescribed and was safe and well tolerated by patients.