BackgroundConventional photodynamic treatment (cPDT) of thin basal cell carcinomas (BCCs) has uncomfortably high rates of incomplete clearance. Incomplete clearance/recurrence rates for superficial BCCs are as high as 40% and even higher for tumours treated on the head and neck. Our experience has been that flushing is more pronounced on the head and neck during cPDT photoactivation. We postulated that haemoglobin, although delivering oxygen, may be acting as a competing chromophore.ObjectivesTo determine whether a 2-phased photoactivation protocol, in which blood is removed before the second phase intense pulsed light (IPL) activation, improves clearance rates.MethodsRetrospective observational study of 206 treatment-na & iuml;ve BCCs <= 1 mm thickness treated over a 7-year period with a 2-phased photoactivation protocol ('biphasic PDT'). The first phase consists of conventional red-light activation (20-37 Jcm-2). Second phase photoactivation uses IPL (30-45 Jcm-2) delivered with sufficient mechanical pressure in the handpiece to blanch the skin. Optical coherence tomography (OCT) has been used to aid in lesion diagnosis, to establish suitability of tumour for treatment and to improve verification of treatment outcomes.MethodsRetrospective observational study of 206 treatment-na & iuml;ve BCCs <= 1 mm thickness treated over a 7-year period with a 2-phased photoactivation protocol ('biphasic PDT'). The first phase consists of conventional red-light activation (20-37 Jcm-2). Second phase photoactivation uses IPL (30-45 Jcm-2) delivered with sufficient mechanical pressure in the handpiece to blanch the skin. Optical coherence tomography (OCT) has been used to aid in lesion diagnosis, to establish suitability of tumour for treatment and to improve verification of treatment outcomes.ResultsIn the final group of 175 tumours, of which most were located on the head and neck and over 40% were nodular, there were only four incomplete treatments over a 2-year median follow-up period (up to 7 years). The few incomplete clearances were easily managed.ConclusionsOne or two biphasic photodynamic treatments are highly effective (98% clearance) in thin, treatment-na & iuml;ve BCCs (<= 1 mm in thickness) selected on clinical and OCT assessment.

Background Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics.Objectives To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion.Methods This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients' medical records and compared with the app's outcome and other lesion data.Results In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928-0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively.Conclusions The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma. We investigated the diagnostic performance of an AI-based decision support in the form of a mobile app to detect melanoma when used by primary care physicians. The app proved to have high levels of diagnostic accuracy in distinguishing melanomas from other skin lesions. We conclude that it appears to be a potentially valuable diagnostic aid for the primary care physician in the assessment of skin lesions of concern.

Background The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. Materials and methods 1 x 1 cm HD-MAP patches containing 5000, 250-mu m long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. Results Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. Conclusions Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this papers demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and physical properties to understand how different excipients affect these aspects, comparing one starch particle-stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex vivo skin hydration measurements. The results show that sensorial attributes related to the application phase can be predicted with rheology, while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial afterfeel.

Significance: Tissue simulating phantoms are an important part of validating biomedical optical techniques. Tissue pathology in inflammation and oedema involves changes in both water and hemoglobin fractions.

Aim: We present a method to create solid gelatin-based phantoms mimicking inflammation and oedema with adjustable water and hemoglobin fractions.

Approach: One store-bought gelatin and one research grade gelatin were evaluated. Different water fractions were obtained by varying the water-to-gelatin ratio. Ferrous stabilized human hemoglobin or whole human blood was added as absorbers, and the stability and characteristics of each were compared. Intralipid® was used as the scatterer. All phantoms were characterized using spatial frequency domain spectroscopy.

Results: The estimated water fraction varied linearly with expected values (R2  =  0.96 for the store-bought gelatin and R2  =  0.99 for the research grade gelatin). Phantoms including ferrous stabilized hemoglobin stayed stable up to one day but had methemoglobin present at day 0. The phantoms with whole blood remained stable up to 3 days using the store-bought gelatin.

Conclusions: A range of physiological relevant water fractions was obtained for both gelatin types, with the stability of the phantoms including hemoglobin differing between the gelatin type and hemoglobin preparation. These low-cost phantoms can incorporate other water-based chromophores and be fabricated as thin sheets to form multilayered structures.

Actinic keratosis is the most common actinic lesion in fair-skinned populations. It is accepted as an indicator of actinic skin damage and as an occasional precursor of squamous cell carcinoma. The aim of this study was to investigate, in a cohort of patients with a diagnosis of actinic keratosis, the relative risk of developing skin cancer during a follow-up period of 10 years. This registry-based cohort study compared a cohort of 2,893 individuals in south-eastern Sweden, who were diagnosed with actinic keratosis during the period 2000 to 2004, with a matched-control cohort of 14,668 individuals without actinic keratosis during the same inclusion period. The subjects were followed for 10 years to identify skin cancer development in both cohorts. Hazard ratios with 95% confidence intervals (95% CI) were used as risk measures. Individuals in the actinic keratosis cohort had a markedly higher risk for all skin cancer forms compared with the control cohort (hazard ratio (HR) 5.1, 95% CI 4.7-5.6). The relative risk was highest for developing squamous cell carcinoma (SCC) (HR 7.7, 95% CI 6.7-8.8) and somewhat lower for basal cell carcinoma (BCC) (HR 4.4, 95% CI 4.1-5.0) and malignant melanoma (MM) (HR 2.7 (2.1-3.6). Patients with a diagnosis of actinic keratosis were found to be at increased risk of developing SCC, BCC and MM in the 10 years following diagnosis of actinic keratosis. In conclusion, a diagnosis of actinic keratosis, even in the absence of documentation of other features of chronic sun exposure, is a marker of increased risk of skin cancer, which should be addressed with individually directed preventive advice.

Background: Hyaluronic acid (HA), a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to be an important factor for keratinocyte activation and re-epithelialization. The experimental hypothesis of this study was that HA accelerates re-epithelialization, and we aimed to investigate the effect of exogenous intradermal HA during deep dermal, incisional wound healing in vivo in humans, the primary endpoint being re-epithelialization. Methods: A total of 8 standardized deep dermal incisional wounds (depth 1.6mm, width 1.8mm) per subject were induced in 10 healthy volunteers. Two of the wound sites per subject were pretreated with injections of HA and 2 with saline solution. At 2 time points (24 hours and 14 days), 2 biopsies for each treatment group (one for histology and one for proteomics) were taken. Skin erythema was measured at 24-hour intervals for 14 days as a surrogate measurement of inflammation. Results: At 24 hours, 8 of 9 wounds pretreated with HA showed complete re-epithelization, whereas none of the wounds pretreated with saline had re-epithelized. Wounds pretreated with HA also showed a 10-fold regulation of 8 identified proteins involved in wound healing compared to wounds treated with saline solution. No difference in inflammation, as measured as erythema, could be seen between any of the groups. Conclusions: We conclude that HA accelerates re-epithelialization and stimulates an altered protein expression in vivo in human deep dermal incisional skin wounds, but has no effect on the inflammation process as measured by erythema.

BACKGROUND: In the light of increasing skin cancer incidences worldwide, preventive measures to promote sun protection in individuals with risky sun habits have continued relevance and importance.

AIM: To report the long-term effect of individualised sun protection advice given in primary health care (PHC), on sun habits and sun protection behaviour.

DESIGN & SETTING: In 2005, 309 PHC patients were enrolled in a randomised controlled study performed in a Swedish PHC setting.

METHOD: At baseline, the study participants completed a Likert scale-based questionnaire, mapping sun habits, propensity to increase sun protection, and attitudes towards sun exposure, followed by randomisation into three intervention groups, all receiving individualised sun protection advice: in Group 1 (n = 116) by means of a letter, and in Group 2 (n = 97) and 3 (n = 96) communicated personally by a GP. In Group 3, participants also underwent a skin ultraviolet-sensitivity phototest, with adjusted sun protection advice based on the result. A repeated questionnaire was administered after 3 and 10 years.

RESULTS: Statistically significant declines were observed in all groups for sun exposure mean scores over time. When using a cumulative score, according to the Sun Exposure and Protection Index (SEPI), significantly greater decrease in SEPI mean score was observed in Groups 2 and 3 (GP), compared to Group 1 (letter); P<0.01. The addition of a phototest did not enhance the effect of the intervention.

CONCLUSION: Individualised sun protection advice mediated verbally by the GP can lead to sustained improvement of sun protective behaviour.