Daily Cosmetic Research Analysis
Three high-impact studies span surgery, dermatology, and genetic epidemiology. A drug-target Mendelian randomization suggests ANGPTL3 inhibition (evinacumab) may reduce psoriasis risk. A network meta-analysis identifies upadacitinib and dupilumab as leading options for adolescent atopic dermatitis, while a prospective fluorescence-guided technique (L-ICG) in breast-conserving surgery achieved low final positive margin rates with excellent cosmetic satisfaction.
Summary
Three high-impact studies span surgery, dermatology, and genetic epidemiology. A drug-target Mendelian randomization suggests ANGPTL3 inhibition (evinacumab) may reduce psoriasis risk. A network meta-analysis identifies upadacitinib and dupilumab as leading options for adolescent atopic dermatitis, while a prospective fluorescence-guided technique (L-ICG) in breast-conserving surgery achieved low final positive margin rates with excellent cosmetic satisfaction.
Research Themes
- Drug-target Mendelian randomization guiding therapeutic repurposing in dermatology
- Comparative effectiveness of systemic therapies for adolescent atopic dermatitis
- Fluorescence image-guided breast-conserving surgery optimizing margins and cosmesis
Selected Articles
1. Genetically mimicked effects of evinacumab on psoriasis: a drug target Mendelian randomization study.
Two-sample Mendelian randomization using large GWAS datasets indicates that genetically higher triglycerides and LDL-C increase psoriasis risk and that genetically mimicked ANGPTL3 inhibition (as with evinacumab) lowers risks of psoriasis and arthropathic psoriasis. These results support lipid modulation—particularly via ANGPTL3—as a potential preventive or therapeutic strategy in psoriasis.
Impact: Provides causal inference linking lipid pathways to psoriasis and nominates ANGPTL3 inhibition as a repurposable therapeutic target. Bridges cardiometabolic and dermatologic therapeutics via drug-target MR.
Clinical Implications: Supports consideration of clinical trials testing evinacumab or ANGPTL3 inhibitors for psoriasis and psoriatic arthritis prevention or control, particularly in dyslipidemic patients; encourages integrated management of lipid abnormalities in psoriasis.
Key Findings
- Each SD increase in triglycerides genetically increased psoriasis risk (OR 1.17; 95% CI 1.03–1.32).
- Each SD increase in LDL-C genetically increased psoriasis risk (OR 1.22; 95% CI 1.05–1.43) and was associated with arthropathic psoriasis (OR 1.30), psoriasis vulgaris (OR 1.87), and guttate psoriasis (OR 2.19).
- Genetically mimicked ANGPTL3 inhibition (evinacumab) reduced psoriasis risk (OR 0.752 per SD TG reduction) and arthropathic psoriasis risk (OR 0.266 per SD LDL-C reduction).
Methodological Strengths
- Two-sample Mendelian randomization leveraging large-scale GWAS (FinnGen and UK Biobank).
- Subtype analyses and lipid-specific instruments increase granularity and robustness.
Limitations
- MR assumptions (e.g., no horizontal pleiotropy) may be violated and cannot be fully tested.
- Findings reflect lifelong genetic exposure; translatability to short-term pharmacologic intervention remains uncertain and ancestry is largely European.
Future Directions: Conduct randomized or adaptive trials of evinacumab in psoriasis/psoriatic arthritis, investigate ANGPTL3’s immunodermatologic mechanisms, and assess benefit–risk in dyslipidemic phenotypes.
BACKGROUND AND OBJECTIVES: Dyslipidemia has been reported to contribute to the psoriasis pathogenesis. Thus, evinacumab, a novel lipid-lowering drug targeting angiopoietin-like 3, may have therapeutic potential to treat and/or manage psoriasis. METHODS AND STUDY DESIGN: Summary statistics were obtained from genome-wide association studies addressing psoriasis (FinnGen Consortium; n=216,752) and serum lipid concentrations (United Kingdom Biobank; n=403,943-440,546). Two-sample Mendelian randomization analyses were conducted to evaluate the associations of serum lipid concentrations and genetically mimicked effects of evinacumab, respectively, with the risks of psoriasis and its subtypes. RESULTS: Genetically determined per standard deviation increase in triglyceride concentrations was associated with increased risk of psoriasis (OR: 1.17, 95% CI: 1.03-1.32, p=0.018), whereas that in low-density lipoprotein-cholesterol (LDL-C) was associated with both psoriasis (OR: 1.22, 95% CI: 1.05-1.43, p=0.011) and its subtypes, including arthropathic psoriasis (OR: 1.30, 95% CI: 1.02-1.65, p=0.032), psoriasis vulgaris (OR: 1.87, 95% CI: 1.16-2.99, p=0.0095), and guttate psoriasis (OR: 2.19, 95% CI: 1.17-4.07, p=0.014). Moreover, genetically mimicked effects of evinacumab, via angiopoietin-like 3 inhibition, significantly reduced the risk of psoriasis (OR: 0.752 per standard deviation reduction in triglycerides, 95% CI: 0.577-0.982, p=0.036) and arthropathic psoriasis (OR: 0.266 per standard deviation reduction in LDL-C, 95% CI: 0.0886-0.799, p=0.018). CONCLUSIONS: The genetically mimicked effect of evinacumab has the potential to reduce the risk of psoriasis and arthropathic psoriasis by lowering circulating triglyceride and LDL-C concentrations, respectively. These findings suggest that evinacumab may help prevent psoriasis and psoriatic arthritis progression in clinical practice.
2. Upadacitinib and Dupilumab Demonstrate Superior Efficacy in the Treatment of Adolescent Atopic Dermatitis: A Network Meta-Analysis.
This PROSPERO-registered network meta-analysis of RCTs in adolescents with moderate-to-severe atopic dermatitis found upadacitinib (30 mg and 15 mg) and dupilumab (300 mg q2w) ranked highest for EASI75 and IGA0/1 responses. Dupilumab and tralokinumab topped itch improvement (PP-NRS4). Safety estimates were unstable due to limited sample sizes, underscoring the need for longer-term data.
Impact: Provides comparative efficacy across leading biologic and JAK inhibitor therapies specifically in adolescents, a population with fewer direct RCT comparisons. Offers actionable ranking to inform treatment selection.
Clinical Implications: Upadacitinib and dupilumab should be prioritized for adolescents with moderate-to-severe AD, with individualized risk–benefit assessments and vigilant safety monitoring. Clinicians should consider tralokinumab for itch improvement and recognize uncertainties in long-term safety.
Key Findings
- Upadacitinib 30 mg/day and 15 mg/day and dupilumab 300 mg q2w ranked highest for EASI75 and IGA0/1 vs placebo and other active comparators.
- Dupilumab 300 mg q2w and tralokinumab 300 mg q2w showed the greatest improvements in PP-NRS4 itch outcomes.
- Safety estimates (TEAEs, SAEs) were unstable due to limited sample sizes; adverse event profiles varied among drugs (e.g., nasopharyngitis, acne).
Methodological Strengths
- Systematic, multi-database search with PROSPERO registration (CRD42023480597).
- Network meta-analysis enabling indirect comparisons across multiple active treatments with sensitivity and bias assessments.
Limitations
- Long-term safety remains uncertain; safety estimates unstable due to limited adolescent sample sizes.
- Heterogeneity in trial designs and endpoints; adolescent-specific dosing and durations vary.
Future Directions: Undertake head-to-head adolescent RCTs with longer follow-up to refine efficacy/safety rankings, include patient-reported outcomes, and evaluate step-up/step-down and combination strategies.
INTRODUCTION: This systematic review and network meta-analysis aimed to compare and evaluate the efficacy and safety of five medications, dupilumab, tralokinumab, upadacitinib, baricitinib, and abrocitinib, for the treatment of adolescent atopic dermatitis (AD), in order to provide decision support to support clinical decision-making by developing more scientifically grounded and effective treatment strategies. METHODS: A comprehensive search was conducted in PubMed, Embase, Web of Science (WoS), and the Cochrane database to collect randomized controlled trials (RCTs) and Phase 3 clinical trials up to April 13, 2024. Supplementary data were retrieved from trial registries, and researchers contacted study authors and pharmaceutical companies when necessary to obtain complete data. Inclusion criteria comprised treatment studies for moderate to severe AD in adolescents aged 12 and above, with outcome measures including efficacy and safety assessments. Data extraction and risk bias assessment were independently performed by two researchers, using Excel for data extraction and the netmeta package in R software for network meta-analysis. Sensitivity analysis and bias risk assessment were conducted to validate the robustness and credibility of the results. Our research protocol was registered in PROSPERO (CRD42023480597) and did not require approval from an Institutional Review Board or written informed consent. RESULTS: In the primary efficacy outcome measures, upadacitinib 30 mg/day, upadacitinib 15 mg/day, and dupilumab 300 mg/2 weeks demonstrated excellent efficacy in EASI75 compared to placebo, significantly outperforming other medications and placebo. Dupilumab 300 mg/2 weeks, upadacitinib 30 mg/day, and upadacitinib 15 mg/day showed excellent treatment effects in IGA0/1. Among the outcome measures for improvement in itch severity rating PP-NRS4, dupilumab 300 mg/2 weeks and tralokinumab 300 mg/2 weeks showed the highest efficacy values. Compared to these medications, baricitinib 1 mg/day exhibited weaker performance across all three indicators, particularly in EASI75 and IGA0/1, with effects approaching no significant difference. Due to limited sample sizes, estimates for treatment-emergent adverse events, serious adverse events (SAEs), and drug-induced adverse events safety indicators were unstable, preventing strong conclusions on safety outcomes. There are significant differences in the incidence rates of adverse reactions such as nasopharyngitis, acne, and AD among various medications. CONCLUSION: Upadacitinib and dupilumab demonstrate strong efficacy and symptom improvement in the treatment of moderate to severe AD in adolescents, particularly in reducing the severity of skin lesions and itchiness. Therefore, these medications should be considered as primary treatment options for adolescents with AD. However, further studies with long-term follow-up and larger sample sizes are necessary to thoroughly investigate the safety profiles of these medications in adolescents. This underscores the importance of closely monitoring the side effects of different drugs during clinical treatment to tailor optimal therapeutic strategies based on individual patient needs.
3. L-ICG as an optical agent to improve intraoperative margin detection in breast-conserving surgery: a prospective study.
In a prospective cohort (n=54), local injection of L-ICG enabled fluorescence-guided BCS with low final positive margin rate (1.9%), wide margins, excellent cosmetic satisfaction, and no serious adverse events over a median 12.8-month follow-up. This technique may reduce re-excisions while preserving cosmetic outcomes.
Impact: Demonstrates a practical fluorescence-guided approach with strong cosmetic satisfaction and low residual disease risk, addressing two key goals in breast-conserving surgery.
Clinical Implications: Surgeons may consider incorporating L-ICG-based FIGS to improve intraoperative margin assessment, potentially reducing re-excision rates while optimizing patient-reported cosmetic outcomes.
Key Findings
- Final positive margin rate was 1.9% after intraoperative management (initial intraoperative positive margin 9.3%).
- Median margin widths were 8 mm (cranial), 5.5 mm (caudal), 6 mm (medial), and 8 mm (lateral).
- Cosmetic outcomes were highly favorable: 100% somewhat/very satisfied when clothed; 98% rated Good/Excellent appearance; no serious adverse events and no relapses at median 12.8 months.
Methodological Strengths
- Prospective design with standardized intraoperative frozen-section assessment.
- Patient-reported cosmetic outcomes and quantitative margin metrics collected.
Limitations
- Single-arm, single-center study without a randomized comparator; potential selection bias.
- Short to mid-term follow-up; oncologic durability and generalizability remain to be established.
Future Directions: Conduct multicenter randomized trials comparing L-ICG FIGS vs standard care on re-excision, local control, cosmesis, and cost-effectiveness; optimize dosing/timing and imaging protocols.
PURPOSE: Precise tumor excision is important in breast-conserving surgery (BCS). This study explores the safety and accuracy of fluorescence image-guided BCS (FIGS) using a lidocaine mucilage-ICG compound (L-ICG). METHODS: 54 patients who underwent BCS from August 2020 to September 2023 were enrolled. L-ICG was locally injected 0.5 cm from the tumor border. FIGS was performed to guide the tumor excision. Frozen sectioning of surgical field biopsies was used to assess the intraoperative margin status. The primary outcome measures were margin width and positive margin rates. Cosmetic outcome was evaluated by the modified version of Breast-QTM Breast-Conserving Therapy Module (Postoperative) and breast cosmetic outcome assessment criteria. RESULTS: The median cranial, caudal, medial, and lateral margin widths were 8 mm (interquartile range [IQR], 3-14), 5.5 mm (IQR, 2-15), 6 mm (IQR, 3-15), and 8 mm (IQR, 3-15), respectively. Five out of 54 (9.3%) patients had an intraoperative positive margin. Intraoperatively extended resection was performed for four patients and mastectomy for the remaining one. This further reduced the positive margin rate to 1.9% at final histopathology. 50 patients received cosmetic outcome evaluation, 100% of them were "somewhat satisfied" or "very satisfied" with the appearance of the operated breast when clothed and 98% of them were scaled as "Good" or "Excellent" in their appearance of the operated breast. No serious adverse events were observed. With a median follow-up of 12.8 months, no events for tumor relapse were observed. CONCLUSION: L-ICG-based FIGS is a promising technique to guide precise tumor excision in BCS.