Background and objectives: Antibiotic resistance in Cutibacterium acnes is undermining topical macrolides and clindamycin, prompting renewed interest in zinc oxide nanoparticles (ZnO-NPs) as non-antibiotic alternatives. We aimed to (i) determine the antimicrobial and anti-inflammatory performance of topical ZnO-NP formulations across in vitro, animal and early human models; (ii) identify physicochemical parameters that modulate potency and tolerance; and (iii) delineate translational gaps and priority design elements for randomised trials. Methods: We systematically searched PubMed, Scopus and Web of Science until 1 June 2025 for in vitro, animal and human studies that evaluated ≤100 nm ZnO-NPs applied topically to C. acnes cultures, extracting data on bacterial load, lesion counts, biophysical skin parameters and acute toxicity. Eight eligible investigations (five in vitro, two animal, one exploratory human) analysed particles 20–50 nm in diameter carrying mildly anionic zeta potentials. Results: Hyaluronic acid-coated ZnO-NPs achieved a sixteen-fold higher selective kill ratio over Staphylococcus epidermidis at 32 µg mL¹, while centrifugally spun polyvinyl alcohol dressings reduced C. acnes burden by 3.1 log₁₀ on porcine skin within 24 h, and plant-derived nanogels generated inhibition zones that were 11% wider than benzoyl-peroxide’s 5%. In human subjects, twice-daily 0.5% hyaluronic–ZnO nanogel cut inflammatory-lesion counts by 58% at week four and lowered transepidermal water loss without erythema. Preclinical safety was reassuring, zero mortality among animals at 100 µg mL¹ and no irritation among patients, although high-dose sunscreen-grade ZnO (20 nm) delayed rat wound closure by 38%, highlighting dose-dependent differences. Conclusions: Collectively, the evidence indicates that nanoscale reformulation markedly augments zinc’s antibacterial and anti-inflammatory performance while maintaining favourable acute tolerance, supporting progression to rigorously designed, adequately powered randomised trials that will benchmark ZnO-NPs against benzoyl peroxide and retinoids, optimise dosing for efficacy versus phototoxicity, and establish long-term dermatological safety.

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646.

Background: Artificial intelligence (AI) has emerged as a transformative technology across dermatological practice, from automated lesion classification to whole-slide pathology analysis. Despite rapid growth in primary studies, a comprehensive synthesis of diagnostic performance, application breadth, and real-world implementation remains lacking. Methods: We conducted a PRISMA systematic review and meta-analysis of studies published from January 2000 to March 2025. We searched the PubMed, Cochrane, and ScienceDirect databases for studies reporting AI diagnostic performance in dermatology. Results: Of 30 included studies (28 valid after exclusion of two retracted publications), 60% focused on melanoma and related lesions. AI diagnostic performance improved markedly over five identified temporal eras (2003–2025), with a pooled AUROC of 0.92 (95% CI 0.87–0.96), Reitsma sensitivity of 0.88 (0.82–0.93), and Reitsma specificity of 0.85 (0.75–0.91). AI matched or surpassed specialist dermatologists in 71% of direct comparisons. Three randomized controlled trials (RCTs) were identified, with heterogeneous findings across different clinical applications: AI assistance significantly improved non-expert diagnostic accuracy in one trial (53.9% vs. 43.8%; p = 0.019), significantly reduced acne severity via personalized treatment recommendations in a second, and showed non-inferior diagnostic performance, but was not cost-effective in the third. The sole cost-effectiveness analysis found AI-assisted surveillance not cost-effective over a 2-year horizon. Conclusions: AI achieves dermatologist-level diagnostic accuracy in controlled settings; however, real-world evidence, algorithmic equity across skin phototypes, and health economic viability remain critical unresolved challenges. Prospective validation, mandatory demographic subgroup reporting, and cost-effectiveness modeling are essential prerequisites for safe and equitable clinical implementation.

Background/Objectives: Glycyl-L-histidyl-L-lysine (GHK) and its copper(II) complex GHK-Cu have been studied for matrix remodeling, inflammation, redox regulation, angiogenesis, and tissue repair, yet the literature frequently treats GHK-Cu as a single active ingredient despite formulation-dependent variation in coordination state, speciation, stability, pharmacokinetics, and toxicity. We critically evaluate GHK-Cu simultaneously as a bioactive metallopeptide and as a drug-delivery cargo, with explicit separation of apo-GHK, canonical GHK-Cu, GHK-derived copper peptides, and non-GHK copper-peptide systems. Methods: We conducted a structured systematic evidence-mapping review of PubMed/MEDLINE, Europe PMC, major publisher platforms, ClinicalTrials.gov, backward citation chains, and official European Union, U.S., and ICH regulatory sources from database inception through 12 August 2026. Biological evidence level and chemical/formulation quality were graded independently using an author-defined two-axis framework. Delivery studies were extracted against a fixed matrix comprising formulation, claimed loading, molar copper occupancy, labile copper, species-resolved release, factorial controls, stability/manufacturability, and objective outcome. Quantitative pooling was not performed because active-entity definitions, formulations, doses, models, comparators, and endpoints were not quantitatively commensurable. Results: Preclinical data consistently support effects on matrix remodeling, epithelial repair, inflammatory/redox regulation, and angiogenesis, but the clinical evidence remains sparse and does not meet contemporary active-entity quality standards. Historical cosmetic reports are small or incompletely characterized; a 13-participant post-CO2-laser study was negative on objective endpoints, whereas a 2026 18-participant split-face eyebrow study reported positive cosmetic hair outcomes but did not define GHK-Cu speciation or local exposure. The ongoing phase 2 acute-wound study NCT07437586 remains recruiting and has no efficacy results; its registration cannot be used as evidence of clinical translation. Across delivery studies, particle size, polydispersity, encapsulation efficiency, total peptide/copper content, and bulk release are often reported, whereas molar occupancy, labile copper, and release of intact GHK-Cu versus apo-GHK/free copper are usually not resolved. Conclusions: Translation is limited less by biological plausibility than by pharmaceutical definition and evidence attribution. We define the “active pharmaceutical entity” operationally as the reproducible chemical state intended to mediate pharmacology at administration, not as an established regulatory designation or a claim that one immutable molecular species persists in biological fluids. We further propose, explicitly as an author-derived development framework rather than a consensus standard, a control strategy based on molar occupancy, route-specific labile copper specifications, orthogonal speciation, mechanism-linked potency, species-resolved release, factorial controls, route-specific safety decision thresholds, ICH-aligned stability, and GMP-scalable manufacture. Until these requirements are met and controlled clinical efficacy is demonstrated, GHK-Cu should be regarded as a promising but unproven therapeutic cargo rather than a clinically validated regenerative drug.

Background/Objectives: General cardio-oncology guidance describes cardiovascular toxicity from BRAF/MEK inhibitors and immune checkpoint inhibitors (ICIs), but it does not resolve how treatment decisions should change when heart failure (HF) is already present. This critical narrative review separates direct HF-specific evidence from indirect evidence and proposes an HF-centered framework for systemic melanoma. Methods: MEDLINE/PubMed, Embase, and the Cochrane Library were searched for English-language sources published from January 2015 to April 2026, with targeted guideline, prescribing-information, interaction, and geriatric-oncology updates through July 2026. Sources were classified as direct, indirect, or extrapolated. This review follows SANRA principles but does not claim systematic-review conduct, pooled estimates, formal risk-of-bias assessment, or GRADE certainty. Results: Only case-level evidence directly describes systemic melanoma treatment in established HF; most cardiotoxicity rates are derived from selected longitudinal and real-world cohorts. We therefore organize decisions across four domains: HF phenotype and current stability; oncological urgency and alternatives; treatment-specific toxicity phenotype; and detectability, reversibility, and patient priorities. Each domain is graded ordinally and generates its own decision output, and explicit precedence rules resolve situations in which several domains are simultaneously abnormal; the pathway from assessment to documented output is presented as a decision flowchart and applied to illustrative clinical cases. This approach modifies interpretation of symptoms, biomarkers, ventricular function, surveillance, drug interactions, treatment interruption, and rechallenge. Every actionable statement is labeled as guideline-supported or author-proposed, therapy-specific baseline and follow-up monitoring are tabulated separately for each treatment class, and heart failure with preserved ejection fraction is addressed as a phenotype in which clinical deterioration may occur without any change in ejection fraction. Patient-level priorities in older adults—survival, quality of life, avoidance of hospitalization, tolerance of frequent monitoring, oral versus infusion treatment, and functional expectation—are specified as items to be recorded rather than inferred. Conclusions: Stable HF is not an automatic contraindication to effective melanoma therapy, whereas recent or active decompensation requires stabilization or monitored treatment when oncological delay is unsafe. The proposed framework operationalizes guideline principles for an understudied population while making the limits of the evidence explicit. It makes a procedural rather than an empirical claim: it is a transparent structure for documenting a decision that must be made anyway, not an algorithm derived from or validated against outcome data.