Interobserver agreement on line-field confocal optical coherence tomography image markers in keratinocyte carcinomas and precursor lesions.
Sep,
2024
Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association betwe…
Archives of dermatological research
Melanin-dependent tissue interactions induced by a 755-nm picosecond-domain laser: complementary visualization by optical imaging and histology.
Jul,
2023
Fractional picosecond-domain lasers (PSL) induce optical breakdown, which correlates histologically to vacuolization in the epidermis and dermis. In this ex vivo porcine study, we sought to establish a framework for the investigation of laser-tissue interactions and their dependence on melanin density. Light- (melanin index: 24.5 [0-100]), medium- (58.7), and dark-pigmented (> 98) porcine skin samples were exposed to a 755-nm fractional PSL and examined with dermoscopy, line-field confocal optical coherence tomography (LC-OCT), conventional OCT, and subsequently biopsied for digitally stained ex vivo confocal microscopy (EVCM) and histology, using hematoxylin and eosin (HE) and Warthin-Starry (WS) melanin staining. Dermoscopy showed focal whitening in medium- and dark-pigmented skin. Similarly, LC-OCT and OCT visualized melanin-dependent differences in PSL-induced tissue alterations. Vacuoles were located superficially in the epidermis in dark-pigmented skin but at or below the dermal-epidermal junction in medium-pigmented skin; in light-pigmented skin, no vacuoles were observed. Histology confirmed the presence of vacuoles surrounded by areas void of WS staining and disrupted stratum corneum in darker skin. The combined use of optical imaging for multiplanar visualization and histological techniques for examination of all skin layers may mitigate the effect of common artifacts and attain a nuanced understanding of melanin-dependent laser-tissue interactions. read more
Lasers in medical science
Investigating the efficacy and safety of calcipotriol/betamethasone dipropionate foam and laser microporation for psoriatic nail disease-A hybrid trial using a smartphone application, optical coherence tomography, and patient-reported outcome measures.
Dec,
2022
There is a lack of efficacious topical treatments for patients suffering from psoriatic nail disease (PND). We investigated the efficacy of Calcipotriol-Betamethasone Dipropionate (Cal/BD) foam with and without ablative fractional laser (AFL) in patients with PND. A total of 144 nails from 11 patients were treated in a 24-week long, open-label, randomized, intra-patient controlled proof-of-concept hybrid trial. In addition to daily Cal/BD foam application, half of each patient's psoriatic nails were randomized to receive optical coherence tomography (OCT)-guided AFL treatment at baseline, 6-, and 12-week follow-ups. In-clinic assessment (N-NAIL), patient-reported outcomes (PROMs), and drug consumption were supplemented by remote evaluation of 15 subclinical OCT features, smartphone app-based safety monitoring, and photo-based assessment (NAPSI). After 24 weeks of Cal/BD foam treatment, patients achieved a significant improvement (p < 0.001) in both clinical (N-NAIL -76%, NAPSI -68%) and subclinical (OCT -43%) PND severity as well as a 71% reduction in PROMs. AFL-assisted Cal/BD treatment led to higher clinical (N-NAIL -85%, NAPSI -78%) and OCT-assessed (-46%) reduction of PND signs than Cal/BD alone (N-NAIL -66%, NAPSI -58%, OCT -37%), but did not reach statistical significance. Smartphone app images documented adverse events and mild local skin reactions, particularly erythema (75%), laser-induced swelling (28%), and crusting (27%). This hybrid trial demonstrated a reduction in clinical NAPSI and N-NAIL scores, subclinical OCT features, and PROMs, suggesting that Cal/BD foam is a safe and efficacious treatment for PND. Larger trials are warranted to prove the clinical benefit of AFL pretreatment as a Cal/BD delivery enhancer. read more
Dermatologic therapy
The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial.
Oct,
2022
Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%-53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase Aα (cPLAα) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK. read more
BMJ open
Quantitative Comparison of HSF1 Activators.
Aug,
2022
The heat shock response (HSR) pathway is a highly conserved rescue mechanism, which protects the cells from harmful insults disturbing the cellular protein homeostasis via expression of chaperones. Furthermore, it was demonstrated to play crucial roles in various diseases like neurodegeneration and cancer. For neurodegenerative diseases, an overexpression of chaperones is a potential therapeutic approach to clear the cells from non-functional protein aggregates. Therefore, activators of the HSR pathway and its master regulator HSF1 are under close observation. There are numerous HSR activators published in the literature using different model systems, experimental designs, and readout assays. The aim of this work was to provide a quantitative comparison of a broad range of published activators using a newly developed HSF responsive dual-luciferase cell line. Contrary to natural target genes, which are regulated by multiple input pathways, the artificial reporter exclusively reacts to HSF activity. In addition, the results were compared to endogenous heat shock protein expression. As a result, great differences in the intensity of pathway activation were observed. In addition, a parallel viability assessment revealed high variability in the specificity of the drugs. Furthermore, the differences seen compared to published data indicate that some activators exhibit tissue-specific differences leading to interesting assumptions about the regulation of HSF1. read more
Molecular biotechnology
Optical Imaging Visualizes a Homogeneous and Horizontal Band-Like Biodistribution of Large- and Small-Size Hydrophilic Compounds Delivered by Ablative Fractional Laser.
Jul,
2022
The skin barrier generally limits the topical delivery of hydrophilic molecules. Ablative fractional laser (AFL) facilitates cutaneous drug uptake of smaller hydrophilic compounds in several studies. In this imaging-based study, we aim to investigate the cutaneous biodistribution of two different-sized hydrophilic compounds delivered by an ablative fractional CO laser at minimally invasive settings. Intact or CO AFL-pretreated (2.5 mJ/mb and 5% density) ex vivo porcine skin was topically applied with a large or small hydrophilic compound (fluorescence labeled antibody nivolumab (150,000 g/mol, = 4) or ATTO 647N (746 g/mol, = 3)). Samples were incubated for 20 h in a Franz cell setup, whereafter optical coherence tomography (OCT) was used to assess laser channel depth, and ex vivo confocal microscopy (EVCM) was used to assess epidermal thickness and cutaneous biodistribution of nivolumab and ATTO 647N. With an EVCM-assessed median epidermal thickness of 70.3 µm and OCT-assessed ablation depth of 31.9 µm, minimally invasive settings enabled shallow penetration into the mid-epidermis. The AFL-assisted uptake of the antibody nivolumab and the smaller compound ATTO 647N showed a similar homogenous and horizontal band-like biodistribution pattern that reached mid-dermis. No uptake of nivolumab or ATTO 647N was observed in intact skin. In conclusion, AFL-induced mid-epidermal laser channels facilitates the cutaneous delivery of two hydrophilic compounds that are distributed in a similar homogeneous and horizontal band-like pattern, irrespective of their molecular size. read more
Pharmaceutics
Morphometric Optical Imaging of Microporated Nail Tissue: An Investigation of Intermethod Agreement, Reliability, and Technical Limitations.
Aug,
2021
While optical imaging is a useful technique to quantitate morphological differences and treatment effects, comparative investigations of the various techniques are lacking. This study aimed at evaluating intermethod agreement, reliability, and technical limitations of wide-field microscopy (WFM), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) for morphometry by assessing fractionally ablated nail tissue. read more
Lasers in surgery and medicine
Exploring the utility of Deep Red Anthraquinone 5 for digital staining of ex vivo confocal micrographs of optically sectioned skin.
Apr,
2021
We investigated the utility of the fluorescent dye Deep Red Anthraquinone 5 (DRAQ5) for digital staining of optically sectioned skin in comparison to acridine orange (AO). Eight fresh-frozen thawed Mohs discard tissue specimens were stained with AO and DRAQ5, and imaged using an ex vivo confocal microscope at three wavelengths (488 nm and 638 nm for fluorescence, 785 nm for reflectance). Images were overlaid (AO + Reflectance, DRAQ5 + Reflectance), digitally stained, and evaluated by three investigators for perceived image quality (PIQ) and histopathological feature identification. In addition to nuclear staining, AO seemed to stain dermal fibers in a subset of cases in digitally stained images, while DRAQ5 staining was more specific to nuclei. Blinded evaluation showed substantial agreement, favoring DRAQ5 for PIQ (82%, Cl 75%-90%, Gwet's AC 0.74) and for visualization of histopathological features in (81%, Cl 73%-89%, Gwet's AC 0.67), supporting its use in digital staining of multimodal confocal micrographs of skin. read more
Journal of biophotonics
Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials.
Oct,
2019
Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A systematic review and one-arm meta-analysis, including all prospective clinical trials, identified on PubMed, Cochrane Library, and EMBASE databases. Trials with participants as unit of analysis (UOA), n = 13, were analyzed separately from trials with nails as UOA, n = 7. Summary proportions and 95% confidence intervals (95% CI) were calculated. Outcomes were mycological cure, clinical improvement, or complete cure. Twenty-two prospective trials (four randomized controlled trials and 18 uncontrolled trials) with a total of 755 participants were analyzed. Summary proportions with 95% CI for participants as UOA were mycological cure 70.4%, 95% CI 52.2-83.8%; clinical improvement 67.2%, 95% CI 43.2-84.7%; and complete cure 7.2%, 95% CI 1.9-23.5%. High statistical heterogeneity was detected (mycological cure I = 88%, P < 0.01; clinical improvement I = 69%, P < 0.01; complete cure I = 60%, P = 0.11). The current level of evidence is limited and with high heterogeneity, making it difficult to assess the true efficacy of laser treatment for onychomycosis. Larger randomized controlled trials with well-defined methodology are warranted. read more
Lasers in medical science
