Reflectance confocal microscopy as a non-invasive imaging tool in vulvar high-grade squamous intraepithelial lesions and lichen sclerosus: a descriptive morphological study in patients and healthy volunteers

Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross-sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal-dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non-invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease-specific characteristics could make reflectance confocal microscopy a clinical tool to non-invasively aid identification of vulvar premalignancies.Cervix cance

No effect of topical digoxin and furosemide for patients with actinic keratosis

Drug Delivery Technolog

A multimodal, comprehensive characterization of a cutaneous wound model in healthy volunteers

Development of pharmacological interventions for wound treatment is challenging due to both poorly understood wound healing mechanisms and heterogeneous patient populations. A standardized and well-characterized wound healing model in healthy volunteers is needed to aid in-depth pharmacodynamic and efficacy assessments of novel compounds. The current study aims to objectively and comprehensively characterize skin punch biopsy-induced wounds in healthy volunteers with an integrated, multimodal test battery. Eighteen (18) healthy male and female volunteers received three biopsies on the lower back, which were left to heal without intervention. The wound healing process was characterized using a battery of multimodal, non-invasive methods as well as histology and qPCR analysis in re-excised skin punch biopsies. Biophysical and clinical imaging read-outs returned to baseline values in 28 days. Optical coherence tomography detected cutaneous differences throughout the wound healing progression. qPCR analysis showed involvement of proteins, quantified as mRNA fold increase, in one or more healing phases. All modalities used in the study were able to detect differences over time. Using multidimensional data visualization, we were able to create a distinction between wound healing phases. Clinical and histopathological scoring were concordant with non-invasive imaging read-outs. This well-characterized wound healing model in healthy volunteers will be a valuable tool for the standardized testing of novel wound healing treatments.Drug Delivery Technolog

Topical anti-microbial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild-to-moderate atopic dermatitis in a phase 2 randomized controlled trial

BACKGROUND\nOBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION\nDysbiosis and colonization with Staphylococcus aureus is considered to play an important role in the pathogenesis of atopic dermatitis (AD). Recovering this dysbiosis may improve AD symptoms. Omiganan is a synthetic indolicidin analogue antimicrobial peptide with activity against S. aureus and could be a viable new treatment option for AD.\nTo explore the tolerability, clinical efficacy and pharmacodynamics of omiganan in mild-to-moderate AD.\nEighty patients were randomized to omiganan 1%, 1.75%, 2.5% or vehicle twice daily for 28 days on all lesions. Weekly visits included clinical scores, and microbiological and pharmacodynamic assessments of one 'target lesion'.\nIn all omiganan treatment groups dysbiosis was recovered by reducing Staphylococcus abundance and increasing diversity. A reduction of cultured S. aureus was observed in all omiganan treatment groups, with a significant reduction for omiganan 2.5% compared to vehicle (-93.5%, 95%CI=-99.2%/-28.5% p=0.02). No significant clinical improvement was observed.\nTopical administration of omiganan twice daily for up to 28 days in patients with mild-to-moderate AD led to a recovery of dysbiosis, but without clinical improvement. Therefore, a mono-treatment that selectively targets the microbiome does not appear to be a successful treatment strategy in mild-to-moderate AD