MétaCan
Menu
Back to cohort
Record W4380301245 · doi:10.1016/j.jaci.2023.05.026

Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment

2023· article· en· W4380301245 on OpenAlexfundno aff
Eric L. Simpson, Patrick M. Schlievert, Takeshi Yoshida, Stephanie Lussier, Mark Boguniewicz, Tissa Hata, Zelma C. Chiesa Fuxench, Anna De Benedetto, Peck Y. Ong, Justin Ko, Agustin Calatroni, Amanda K. Rudman Spergel, Marshall Plaut, Sally A. Quataert, Samuel H. Kilgore, Liam F. Peterson, Ann Gill, Gloria L. David, Tim R. Mosmann, Steven R. Gill, Donald Y.M. Leung, Lisa A. Beck

Bibliographic record

VenueJournal of Allergy and Clinical Immunology · 2023
Typearticle
Languageen
FieldMedicine
TopicDermatology and Skin Diseases
Canadian institutionsnot available
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesSanofi GenzymeMedical Center, University of RochesterUniversity of California, San DiegoRegeneron PharmaceuticalsNational Institutes of HealthLEO PharmaSanofiKyowa Hakko KirinPfizerUniversity of RochesterIncyteKyowa Kirin Pharmaceutical DevelopmentCastle BiosciencesRibon TherapeuticsDermiraAmgenGenentechNational Jewish HealthKiniksa PharmaceuticalsGeorgia Clinical and Translational Science AllianceUniversity of PennsylvaniaOregon Health and Science UniversityValeant Pharmaceuticals InternationalGaldermaEli Lilly and CompanyGlaxoSmithKline
KeywordsDupilumabAtopic dermatitisStaphylococcus aureusMedicineDermatologyReduction (mathematics)Methicillin-resistant Staphylococcus aureusBiologyBacteriaMathematics

Abstract

fetched live from OpenAlex

Background Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities and Staphylococcus aureus skin colonization and infections. S. aureus is thought to play a role in AD severity. Objective We characterized the changes in the host-microbial interface in AD subjects following type 2 blockade with dupilumab. Methods Participants (n=71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple timepoints: S. aureus and virulence factor quantification, 16s rRNA microbiome, serum biomarkers, skin transcriptomic analyses and peripheral blood T-cell phenotyping. Results At baseline, 100% of participants were S. aureus colonized on the skin surface . Dupilumab treatment resulted in significant reductions in S. aureus after only 3 days (compared to placebo); 11 days before clinical improvement. Participants with the greatest S. aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S. aureus cytotoxins (day 7), perturbations in Th17 subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil and complement pathways (day 7) were also observed. Conclusion Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S. aureus abundance in AD subjects, and this reduction correlates with reductions in the type 2 biomarker, CCL17 and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for Th17, neutrophils and complement activation as potential mechanisms to explain these findings.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.331
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designCase report
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations88
Published2023
Admission routes1
Has abstractno

Explore more

Same venueJournal of Allergy and Clinical ImmunologySame topicDermatology and Skin DiseasesFrench-language works237,207