Palatability of two different formulations of urea for the treatment of hyponatremia: A double-blind, randomized, cross-over study.

BACKGROUND AND AIMS: Hyponatremia (HN) is the most common disorder of electrolytes encountered in clinical practice. Considering that HN is associated with high morbidity and mortality, it is important to identify treatments for these patients. The therapeutic approaches for HN depend on the severity and the character of the pathology (acute vs. chronic). Among intervention strategies, oral urea represents an effective, safe, and well-tolerated therapeutic approach in the management of chronic hyponatremia. Oral ureal is commonly prepared as a galenic formulation that is usually associated with distaste problems. A double-blind, randomized, cross-over clinical trial was conducted to evaluate and compare the palatability of two different urea formulations: a commercial urea formulation and a galenic one (trial registered on www.isrctn.com, number: ISRCTN18369035). MATERIALS AND METHODS: Thirty-six healthy subjects (18 female and 18 male, median age 55 years) were enrolled in the study and randomized to consume 7 g of formulation A (commercial formulation) or formulation B (galenic formulation) twice a day away from meals, solubilizing the products in 125 mL of water (T0). After three days of a wash-out, the formulations were crossed-over and consumed twice a day away from meals (T4). After the consumption of products, both in the morning and the evening, participants completed a specific questionnaire to evaluate the products' palatability. RESULTS: The commercial formulation was globally more appreciated than the galenic one, in terms of smell, taste, and aftertaste. The commercial formulation was better accepted as a potential treatment in 44 % of subjects compared to 14 % of subjects for galenic formulation. CONCLUSIONS: The clinical trial confirmed the better palatability of the commercial oral urea formulation, containing citrus flavor, which therefore represents a therapeutic strategy that could improve adherence to the therapy in chronic patients with hyponatremia.

Folliculotropism in Actinic Keratoses in Patients not Responding to Treatments: A Pilot Study.

Dear Editor, Actinic keratoses (AK) have a high prevalence in the general population, with greater rates in Caucasian patients after the fourth and fifth decades of life (37.5-60.0%) (1,2). Standard histopathologic reporting of AKs does not provide information on the presence of atypical keratinocytes extending to the hair follicle, also defined as folliculotropism (FLC). Commonly, atypical cells in AKs do not present FLC, but this feature can be observed in bowenoid AKs with full-thickness epidermal atypia (3,4). FLC has been considered a possible element enhancing the chances of a progression toward invasive SCC (iSCC). Fernandez-Figueras et al. (3) reported that the depth of FLC in AKs was correlated with the invasiveness of associated iSCC. Pandey et al. (5) reported a positive association between AKs with FLC and history of invasive cutaneous cancer or melanoma, more often in men at an older age. The role of FLC in cutaneous melanoma is still debated, but it is considered a parameter that may correlate with treatment response in lentigo maligna and disease progression or recurrences in invasive tumors (6,7). These studies draw particular attention to the potential role of hair bulge compartment stem cells in favoring tumor progression through the expression of adhesion molecules, cytokines, and growth factor receptors (8). Aks are known to have a high recurrence rate after topical treatment (1). The risk of evolution to an iSCC is not completely clear, but it has been estimated to be around 0.6% at 12 months and up to 2.5% at 48 months (1,3,7). Considering the possible progression and the heavy burden of AK treatments, including the economic burden, it is imperative to focus on histopathologic features associated with treatment failure. The aim of this preliminary study was to assess the histopathologic features, specifically FLC, of AK samples from patients considered "non-responders" to specific topical treatments. A secondary endpoint was to assess the clinical/dermoscopic features. Patients were considered "non-responders" if the lesions persisted after two alternated completed cycles of treatments with ingenol mebutate, imiquimod, diclofenac 3%, or 5-fluoruracil. Patients with a positive history of immunosuppression or genetic diseases were excluded. The study was approved by the local Ethics Committee. Slides of AKs diagnosed at the Laboratory of Dermatopathology, University of Bologna, Italy from January 2016 to October 2018 were reviewed by two dermatopathologists (CM, PAF). 155 "non-responder" AKs of five main histopathologic subtypes were included, classified from grade I to III according to the Roewert-Huber classification (9) (Table 1). The proliferative and atrophic histopathologic subtypes of AKs were detected in 33.6% and 30.4% samples, respectively. FLC was observed in 75.3% of the cases, subdivided into two categories, periadnexal (48.9%) and intraadnexal (26.4%). Periadnexal FLC was detected in 31.0% of atrophic and in 50.3% of proliferative AKs, while intraadnexal FLC was found in 48.7% and 29.2%, respectively (Figure 1, a, b). At dermoscopy, most lesions had been classified as grade I or II (38.8% and 45.8%), and only 15.4% as grade III, showing an unexpected non-response to treatment according to the dermoscopic criteria. In contrast, almost half of the AKs were classified as grade III at histology, revealing a discrepancy between the dermoscopic grading and histological findings in a majority of cases (77.4%) (Figure 2, c, d). Furthermore, atrophic and proliferative AKs accounted for 64.0% of total cases, and these are the variants associated with a higher probability of evolution toward an iSCC (10). The clinical/histological discrepancy has already been reported in the literature (9) and may represent a misleading factor for treatment choice and outcomes. We believe that a comparative analysis with dermoscopy and histology should be performed in non-responding AKs, in order to choose the best therapeutic option. In fact, some superficial treatments (such as cryotherapy) may not provide a good response in deep hair follicles (4). We also suggest encouraging greater focus on FLC and its description in pathology reports. This is a preliminary observational study, but it reinforces the need to further larger clinical studies investigating the role of specific histopathologic parameters in AKs, including FLC, that may correlate with treatment outcomes.

Efficacy and tolerability of an oral supplement containing amino acids, iron, selenium, and marine hydrolyzed collagen in subjects with hair loss (androgenetic alopecia, AGA or FAGA or telogen effluvium). A prospective, randomized, 3-month, controlled, assessor-blinded study.

BACKGROUND: Oral supplementation with some amino acids (like methionine, taurine, and cysteine) could be useful in subjects with hair loss conditions such as androgenic alopecia (AGA or FAGA) or telogen effluvium (TE). Hydrolysed collagen (HC) oral supplementation has demonstrated to have beneficial effects on nail and skin health and could improve hair growth. A food supplement in tablet formulation containing hydrolysed fish-origin collagen (300 mg/dose), taurine, cysteine, methionine, iron, and selenium has been recently available. To date no controlled data are available regarding the clinical efficacy of this product as adjuvant to hair loss specific treatments in these clinical conditions. STUDY AIMS: To evaluate and compare the efficacy and tolerability of an oral supplementation based on HC and amino acids in subjects with hair loss due to AGA/FAGA or chronic TE in combination with drug treatments in comparison with drug treatments alone. METHODS AND SUBJECTS: In a prospective, 12-week, randomized, assessor-blinded controlled trial 83 subjects (mean age 41 ± 16 years; 26 men and 57 women) were enrolled in the study. Fifty-nine subjects suffered from AGA/FAGA (Hamilton I-VA, Ludwig I-1, II-2) and 24 from chronic TE. Subjects were randomized to oral supplementation (1 tablet day) in combination with the specify drug treatment decided by the investigator according to the type of hair loss (AGA/FAGA or TE) (Group A; N = 48) or to specific drugs treatment only (Group B; N = 35). The main outcome of the trial was the clinical efficacy evaluation using a 7-point global assessment score (GAS) (from +3: Much Improved to -3 Much worsened; with score 0 representing no modification). The GAS score was evaluated using standardized photographs by an investigator unaware of the treatment groups at week 6 and at week 12. A secondary outcome was the evaluation of acceptability of the treatment regimen using a 10-point evaluation score. RESULTS: Seventy-six participants (91.6%) completed the 12-week study period. The GAS score at week 6 was 0.5 ± 0.2 in group A and 0.0 ± 0.1 in Group B (p < 0.05; Mann-Whitney). At week 12 the GAS score in Group A was statistically significant higher in comparison with Group B (1.67 ± 0.16 and 0.66 ± 0.20, p < 0.001; Mann-Whitney test). A higher percentage of Group A subjects achieved a GAS score of ≥2 in comparison with group B (50% vs. 23%). The oral supplement was generally well tolerated. CONCLUSION: An oral supplement containing hydrolysed fish-origin collagen, taurine, cysteine, methionine, iron, and selenium has demonstrated to improve the clinical efficacy of specific anti-hair loss treatments in subjects with AGA/FAGA or chronic TE.

Successful Treatment of Nail Lichen Planus with a Lacquer Containing Urea, Keratinase, and a Retinoid Molecule: Report of 10 Cases.

Lichen planus is chronic inflammatory mucocutaneous disease. Involvement of nails (nail lichen planus: NLP) could be the only manifestation or it could be associated with the other typical skin and mucous localizations. Typical NLP alterations are linear nail bed dyschromia, longitudinal ridging, splitting, onycholysis, and subungual hyperkeratosis. Pterygium could be observed in advanced stages. Treatment of NLP is challenging. Limited clinical data have suggested that both oral and topical retinoids could be beneficial. Recently, a nail lacquer containing urea (20%), keratinase from Bacillus licheniformis, and hydroxipinacolone retinoate (U-KR lacquer) has been available. This product has shown good efficacy in the treatment of onychodystrophy characterized by onychogryphosis. We have evaluated, in a case series pilot study, the efficacy of this lacquer in subjects with moderate NLP. The product was applied once daily on the affected nails. Ten subjects (6 men and 4 women, mean age 38 years) after their written informed consent, with clinical NLP (2 subjects with histological confirmation) affecting foot or hand nails (mean number of nails involved: 4; range from 1 to 10), were treated for 12 consecutive weeks with U-KR, one application per day. The main endpoint was the evolution of a NLP severity score (NLPSS) evaluating 7 nail signs: grade of onycholysis, longitudinal ridging, splitting, grade of subungual hyperkeratosis, nail bed thickening, dyschromia, and nail pitting. For each item, a 4-grade score (from 0: no sign to 3: severe) was used (range of NLPSS from 0 to 21). At baseline, the NLPSS was 20.8 ± 3. After 12 weeks, the NLPSS showed a significant reduction to 4 ± 8.8, representing an 81% reduction in comparison with baseline value (p = 0.0001), with an absolute difference between means of -16.86 ± 2,586 (95% CI of the difference: from -22.49 to -11.22) The product was very well tolerated. This 10-case pilot study suggests that a nail lacquer with 3 components (urea, keratinase, and a retinoid molecule) could be useful in subjects with NLP. Future controlled trials are warranted to better define the therapeutic potential of this product in NLP treatment.

Efficacy of a retinoid complex plus anti-inflammatory component cream alone or in combination with prebiotic food supplement in adult acne: A randomized, assessor-blinded, parallel-group, multicenter trial on 184 women.

BACKGROUND: Adult female acne (AFA) nowadays is a very common skin condition affecting mainly women aged between 25 and 40. The treatment of AFA could be challenging. STUDY AIM: We evaluate and compare the efficacy and tolerability of a cream formulation containing two retinoid molecules (hydroxypinacolone/retinyl palmitate) combined with Iris Florentina root extract and a complex of three oligopeptides (C) applied twice a day (morning and evening) alone or in combination (C + O) with a food supplement containing a mixture of prebiotic molecules (FOS&GOS) zinc, lactoferrin, and niacinamide. SUBJECTS AND METHODS: In a multicenter, randomized, assessor-blinded, 12-week trial, we assessed the efficacy of these two regimens in the evolution of AFA lesions (non-inflammatory: NI-L; inflammatory: IL; and total number of lesions: TL). Additional efficacy endpoints were the evolution of the 6-point (from 0 to 5) GEA and Adult Female Acne Scoring Tool (AFAST) scores. RESULTS: One hundred and eighty-four women (mean age 32 ± 6 years) with AFA agreed to participate after obtaining informed consent. They were randomized (2:1) to the topical product (n = 123) (Group C) or to the combination (n = 61) (Group C + O) treatment. All enrolled patients concluded the trial with no drop-out. At baseline, NI-L, IL, and TL acne lesion count were 15 ± 9, 9 ± 5, and 24 ± 14 in the Group C and 19 ± 8, 9 ± 4, and 29 ± 10 in Group C + O. In comparison with the number of the acne lesions at the baseline, both treatment regimens induced a significant reduction (p = 0.0001, ANOVA test) at Week 12 in NI-L, IL, and TL by -54%, -63%, and - 59% in Group C and by -55%, -73%, and - 61% in the Group C + O, respectively. At Week 12, the absolute IL count reduction vs. baseline was significantly (p = 0.0158) greater in Group C + O (-7.0) in comparison with Group C (-5.5). The GEA absolute score reduction in Group C + O group was significantly greater in comparison with Group C (-1.5 vs. -1.1; p = 0.0097). In the Group C + O, a greater percentage of success treatment (defined as a GEA score of 0/1 at Week 12) was observed in comparison with Group C (39% vs. 27%; p = 0.06). AFAST score at baseline was 2.4 ± 0.5 in group C and 2.8 ± 0.6 in group C + O. AFAST score was reduced by 21% and by 51% after 6 and 12 weeks of treatment in group C and by 22% and 55% in group C + O, respectively. Both treatment regimens were well tolerated. Not relevant adverse events were recorded. CONCLUSION: A cream containing retinoid molecules and Iris Florentina root extract is effective and well tolerated in the management of AFA. The treatment combination with a prebiotic and anti-inflammatory food supplement offers an additional clinical benefit mainly in reducing inflammatory lesions and improving the severity acne score.

Circulating microRNA biomarkers in melanoma and non-melanoma skin cancer.

INTRODUCTION: Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell, and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy. AREAS COVERED: In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers. EXPERT OPINION: Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings.

Assessment of sinecatechins 10% ointment used as proactive sequential therapy in recurrence rate of genital warts lesions after cryotherapy. The PACT-II Trial (postablation immunomodulator treatment of condylomata with sinecatechins): a prospective assessor-blinded, multicenter, pilot trial.

BACKGROUND: Cryotherapy is commonly used as ablative treatment of external genital warts (EGW). However, after cryotherapy recurrence of lesions affects on average 45% (42-70%) of subjects in the 6 months after the treatment. Sinecatechins 10% are an effective topical treatment of EGW. A low recurrence rate (<6%) was observed in pivotal phase 3 trials conducted with this product. Topical sinecatechins have demonstrated to significantly reduce the recurrence rate of EGW in subjects treated with laser therapy (The PACT-I trial). So far, no prospective data are available regarding the efficacy of sinecathechins as immunomodulator sequential therapy after cryotherapy in EGW subjects. The purpose of this study was to assess the rate of recurrence lesions after the use of topical sinecatechins 10%, as sequential proactive immunomodulation treatment after cryotherapy in subjects with EGW (The PACT-II Trial: the postablation immunomodulator treatment of condylomata with sinecatechins trial) (Trial Registration number: ISRCTN44037479). METHODS: In a prospective, assessor-blinded, multicenter trial a total of 55 subjects with a diagnosis of multiple EGW (36 men and 19 women, mean age 47±10 years) and a mean lesion number of 9±7, after their informed consent, were enrolled in the study. All subjects were treated with cryotherapy (an average of 2 sessions). After the ablative treatment, all subjects were instructed to apply sinecatechin 10% ointment 3 times daily for 4 consecutive months. The primary study endpoint was the evaluation (assessor-blinded) of recurrent lesions after 6 months (2 month of follow-up after the conclusion of topical treatment). The secondary study endpoints were the appearance of new EGW lesions (lesions affecting area not treated by cryotherapy) and the local tolerability. RESULTS: At baseline, the mean number of EGW lesions were 9±7. After cryotherapy, the mean lesions number were reduced to 1.6±1.8. At month 4, EGW mean lesion number were 0.2±0.4 (P=0.0001 vs. after cryotherapy). At month 6, recurrence of lesions was detected in 10 subjects (18%; 95% CI: 9-30%) with an average of 1.4 lesions. Of these recurrent lesions, 6 occurred in completely healed lesions site after cryotherapy and 8 in partially healed ones. New lesions (outside the cryotherapy treated area) were observed in 10 subjects. The product was very well tolerated. No serious side effects were reported. Three subjects reported moderate skin irritation on the application site. CONCLUSIONS: The PACT-II Trial has shown that the recurrence rate of EGW lesions after successful cryotherapy using sinecatechins as immunomodulator sequential therapy is lower in comparison with the percentage documented in the literature without sequential therapy (20 vs. 45%). These results are in line with already published data evaluating the role of sinecatechins after laser therapy (PACT-I trial). Future comparative, double-blind controlled trials assessing the efficacy of different proactive strategies are warranted.

Assessment of clinical efficacy of lidocaine/tetracaine 7%/7% peel cream in fractional microablative laser procedure-associated pain for facial skin aging treatment. A randomized, controlled, single-blind trial.

BACKGROUND: Lidocaine/tetracaine 7%/7% peel cream (L/T-pC) is very effective in reducing pain in several dermatological procedures, such as hair or tattoo laser removal or conventional photodynamic therapy associated pain. Fractional laser resurfacing (FLR) is an effective treatment strategy for facial skin aging. The main drawback of FLR is the procedure-associated pain. So far, no controlled data are available regarding the efficacy of L/T-pC in reducing pain during a full-facial microablative FLR session in subjects with facial skin aging. AIM: To assess the clinical efficacy of L/T-pC in reducing pain during microablative FLR treatment in subjects with facial skin aging. We conducted a prospective, randomized, parallel-group, controlled, single-blind trial, performed in out-patients attending to a Laser Clinic for facial skin aging treatment. SUBJECTS AND METHODS: A total of 30 subjects (4 men, 26 women; mean age 42 ± 10 years; range 28-57) with mild to moderate facial skin aging (Glogau score ≥2), suitable for FLR treatment, were enrolled after their written informed consent. Participants were randomized to L/T-pC application (45 min before the laser treatment with the removal of the cream just before the starting of laser session) (n = 20) or to control (emollient cream; n = 10). FLR was performing using a fractional microablative CO2 laser (Smartxide DOT 2 Deka) using a pulse power of 18 W (range 15-20) and pulse duration of 1.5 msec. The primary endpoint was the comparison of the mean visual analogue score (VAS) values between the two groups using a 10-cm scale (0 = no pain; 10: the most severe pain). The VAS score was measured just after the FLR session. Effective anesthesia (percentage of subjects with a VAS score ≤3) and the assessment of local tolerability and safety of the peel cream were the secondary trial endpoints. RESULTS: All the enrolled subjects concluded the trial. In the L/T-pC group, the VAS mean score was 3.0 ± 1.2. In the control group, the VAS mean score was 8.6 ± 0.5, representing a 65% reduction of the VAS score in the active treated group vs. controls. The difference between the two groups was statistically significant (p = 0.0001; Mann-Whitney test) with an absolute difference of -5 ± 0.4 cm; 95%CI of the difference: from -4.6 to -6.4 cm). Adequate anesthesia (VAS score≤3) was reported in 80% of subjects in the active group vs. 0% in the control arm. The cream was very well tolerated. One subject in the active group manifested moderate/severe edema in the cream application area, subsiding in 6 h. No other side effects were reported. CONCLUSION: The application of L/T pC 7%/7% peel cream before a fractional laser resurfacing session significantly reduced the procedure-associated pain with good tolerability and safety profile.

Efficacy and tolerability of a cream containing modified glutathione (GSH-C4), beta-Glycyrrhetic, and azelaic acids in mild-to-moderate rosacea: A pilot, assessor-blinded, VISIA and ANTERA 3-D analysis, two-center study (The "Rosazel" Trial).

BACKGROUND: Rosacea is a very common, chronic inflammatory disease characterized by flushing, erythema and inflammatory lesions. Increased oxidative stress plays a relevant pathogenetic role in Rosacea. Intracellular Glutathione (GSH) is the main scavenger protective mechanism against increased oxidative stress. An altered GSH metabolism in Rosacea has been described. GSH-C4 is a modified GSH molecule characterized by a better intracellular bioavailability and longer half-life. A daily cream (E-AR) containing GSH-C4 (0.1%) with beta-Glycyrrhetic (0.5%) and azelaic acids (10%), with an SPF of 30, is available. AIM: In a pilot, prospective, two-center, assessor-blinded study we evaluate the efficacy and the tolerability of E-AR cream in subjects with mild to moderate Rosacea treated for 8 weeks. PATIENTS AND METHODS: The main outcomes were the Investigator Global Assessment (IGA) 7-point score (from 0, completely clear; to 6, severe) and the clinical and instrumental erythema severity score (ESS) (from 0 to 4) evaluated in a blinded fashion (randomly coded photographs) at baseline, after 4 (only clinical) and 8 weeks (clinical and instrumental). VISIA evaluation for erythema and lesion counts and ANTERA 3D analysis for skin haemoglobin concentration (a parameter associated with inflammation) were also performed at the same time points. Analysis of primary outcomes was performed on an intention-to-treat basis. Tolerability was evaluated at week 4 and 8 recording spontaneously reported side effects. RESULTS: Thirty subjects (22 women and 8 men; mean age 38 years) were enrolled after their written informed consent. Twenty-six (87%) subjects completed the study phases. Four subjects stopped prematurely the trial due to low skin tolerability (n=3) or lost to follow-up (n=1). At baseline, mean (SD) IGA score was 2.6 (0.9). At week 4, IGA score decreased (NS) to 2.3 (1.2). IGA score decreased significantly (p=0.0001) at week 8 to 1.2 (1) (mean difference 1.3; 95% CI of the difference from 0.9 to 1.7) in comparison with the baseline. The inflammatory mean (SD) lesion count, evaluated clinically, were 5.1(2.5) at baseline, 2.8 (1.9) at week 4, and 1.9 (1.7) at week 8 (P=0.0001; ANOVA Test), representing a 63% reduction. This reduction was confirmed by inflammatory lesions count performed on VISIA pictures (from 4.5 at baseline to 1.7 lesions at week 8). Similar evolution was observed for the clinical and instrumental ESS with a reduction of 56% (clinical) and 48% (VISIA), respectively, at week 8 in comparison with the baseline. ANTERA 3D photographs confirmed the positive evolution observed clinically with a significant reduction (-24%) in hemoglobin content: from 1.88 at baseline to 1.44 at week 8. CONCLUSION: This new GSH-C4, beta-glycyrrethic and azelaic acids cream has shown to be efficacious in mild to moderate rosacea subjects. Local tolerability is in line with other anti-rosacea treatments.

Efficacy and tolerability of short contact therapy with tretinoin, clindamycin, and glycolic acid gel in acne: A randomized, controlled, assessor-blinded two-center trial: The MASCOTTE study.

Retinoids and antibiotics topical treatments are commonly used as first line therapy in mild to moderate acne. However, irritant contact dermatitis is a common side effect of topical retinoids. A strategy to increase local tolerability is the "short contact therapy" (SCT) approach, consisting in the application of the product with the complete removal after 30 to 60 minutes using a non-aggressive cleanser. A gel containing tretinoin 0.02%, clindamycin 0.8%, and glycolic acid 4% in polyvinyl alcohol (MP-gel) has shown to be effective as monotherapy in mild to moderate acne with a tolerability profile similar to other topical retinoids. So far, no trials have been performed with this gel comparing the tolerability profile of SCT with standard application therapy (SAT). We conducted a 2-center randomized parallel groups, controlled, assessor-blinded study, comparing MP-gel applied as SCT in comparison with MP-gel used as SAT (The "MASCOTTE" trial). Forty-six subjects (nine men and 37 women, mean age 23 ± 4 years, range 18-31 years) with mild-to-moderate acne were enrolled, after their written informed consent in a randomized, parallel groups controlled, assessor-blinded 8-week trial. Twenty-three were assigned to MP-gel once daily (evening application) using the SCT approach (ie, complete removal of product after 1 hour using a gentle cleanser), and 23 were randomized to the SAT approach with the same gel. The primary endpoint was the evolution of the tolerability score (TS) assessed evaluating four items: erythema, dryness, stinging, and burning, using a 4-point score scale (from 0: no symptom to 3: severe symptom). Secondary endpoints were the evolution of global acne grading system (GAGS) score (range: from 0 to >39) and the investigator global assessment (IGA of acne severity) score (range from 0 to 4). TS was evaluated at 2, 4, and 8 weeks. GAGS and IGA scores were evaluated at baseline and at week eight. At week eight, an efficacy global score (EGS) (from 1: no efficacy to 4: very good efficacy) and a tolerability global score (TGS) (from 1: very low tolerability to 3: very good tolerability) evaluation were also done. All the evaluations were performed by an investigator unaware of treatment groups allocation (SCT or SAT). Thirty-eight subjects (83%) completed the 8-week treatment period. Eight subjects (two in the SCT group and six in the SAT group) dropped out prematurely due to low skin tolerability. In the SCT the TS at week two was 1.3 ± 1.7, in the SAT group TS was significantly higher (3.1 ± 1.7) (P = .028). TS was significantly lower in SCT group vs SAT also at weeks four and eight (P = .01; ANOVA test). The GAGS score at baseline was 19 ± 7 in the SCT group and 23 ± 4 in the SAT group (NS). At week 8 the GAGS score in SCT was significantly reduced to 8.5 ± 2.8 (-55%) (P = .001 vs baseline) and was also significantly lower in comparison with SAT group (8.5 vs 15; P = .0054). The IGA scores at baseline were 1.9 ± 0.6 in SCT and 2.4 ± 0.7 in SAT group. At week eight, in comparison with baseline values IGA score was reduced significantly by 48% in SCT and by 30% in SAT. EGS and TGS were significantly higher (better clinical efficacy and better tolerability) in SCT in comparison with SAT (3.6 ± 0.5 and 2.9 ± 0.3 vs 2.7 ± 0.6 and 1.5 ± 0.7; respectively). This tretinoin, clindamycin, glycolic acid gel, applied as SCT, has shown a better skin tolerability and at least a comparable clinical efficacy in comparison with the standard application modality in the treatment of mild-to-moderate acne. The SCT therefore could be an effective treatment strategy which could improve subjects' compliance and adherence.

Inter-observer evaluation of erythema-directed photography for the assessment of erythema and telangiectasias in rosacea.

BACKGROUND: Persistent centrofacial erythema associated with telangiectasias is one of the most common phenotypes of rosacea in clinical practice, and the assessment of each component is crucial as each of them may require a different approach. The aim of this study was to evaluate the inter-observer reliability of standard photography vs erythema-directed photography for the assessment of erythema and telangiectasias in rosacea. MATERIALS AND METHODS: One hundred full-face images of 50 rosacea patients (50 standard photographs and 50 erythema-directed digital photographs) were evaluated by 8 independent experienced dermatologists using a 5-item score for erythema and telangiectasias, respectively. Inter-rater reliability, by comparing erythema and telangiectasias scores and calculating the percentage of agreement between evaluators, was assessed and the strength of agreement using the Cohen's Kappa values (95% CI) was calculated. RESULTS: Poor and fair strength of agreement for erythema and telangiectasias using standard photography vs moderate and good strength of agreement using erythema-directed digital photography was found. CONCLUSION: Erythema-directed digital photography may provide a better strength of agreement and higher reliability among independent observers compared to standard photography in the assessment of erythema and telangiectasias in rosacea, thus suggesting new horizons for digital appraisal of skin diseases.

Efficacy and safety of a new topical gel formulation containing retinol encapsulated in glycospheres and hydroxypinacolone retinoate, an antimicrobial peptide, salicylic acid, glycolic acid and niacinamide for the treatment of mild acne: preliminary results of a 2-month prospective study.

BACKGROUND: Acne vulgaris is a common and chronic skin disease that impacts on physical and psychological perceptions. Combination therapy with topical retinoids and antimicrobial agent is considered the preferred approach for most of the subjects affected by mild-to-moderate acne. A correct therapeutic management should include a prolonged treatment to ensure therapeutic success and to prevent recurrences. The aim of this study was to evaluate the efficacy and tolerability of a new topical gel formulation that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate, associated with an anti-microbial peptide (BIOPEP-15) salicylic acid, glycolic acid, and niacinamide as monotherapy in mild acne vulgaris. METHODS: A 2-month prospective study was conducted at the Unit of Dermatology of the Federico II University. Twenty-five patients aged from 14 to 30 years with mild acne of the face (GAGS score ≤ 18) were consecutively enrolled. Each patient was asked to apply the gel formulation once daily in the evening for 8 weeks. The number of acne lesions with VISIA camera system, the global acne grading system (GAGS) score, trans epidermal water loss (TEWL), skin colorimetry (X-rite Spectrocolorimeter), reflectance confocal microscopy exam were evaluated at baseline, after 4 and 8 weeks of treatment for each patient. Tolerability and safety of the product were also evaluated. RESULTS: Twenty-five female patients with a median age of 23.4 were enrolled. Twenty-two (88%) completed the 2-month treatment period visits. At baseline the total acne lesion number, mean (SD), was 5.5 (4) and the GAG score 9 (4). A significant (P=0.001) reduction in number of total acne lesions was observed at week 4 (-57%) and at week 8 (-80%). All patients presented a significant reduction of the GAGS score values: -42% at week 4 and -78% at week 8, confirming the clinical efficacy of the product. At baseline TEWL was 10.2 g/m2/h (1.3) and 10.7 (1.4) at week 8, thus showing that the gel did not impair the skin barrier function. Skin colorimetry was significantly (P=0.0015) reduced by the treatment in comparison with baseline (62 vs. 58). Efficacy of the gel formulation was also confirmed with RCM exams, showing a reduction of dermal inflammation and exocytosis, and an improvement of infundibular hyperkeratinization. We observed that adherence to treatment correlated positively with the improvement of the single parameters. Moreover, side effects such as erythema, dryness, and excessive xerosis were not reported, resulting in a complete adherence to the treatment. CONCLUSIONS: Our findings provide favorable evidences of the efficacy and safety of this new product as a first line treatment in patients with mild acne, or, as a maintenance therapy for prolonged periods after the suspension of a systemic treatment. Furthermore, the tolerability of this topical product and the absence of any side effects increased the adherence to the therapy.

Propylene glycol free 5% minoxidil lotion formulation: cosmetic acceptability, local tolerability, clinical efficacy and in-vitro skin absorption evaluations.

BACKGROUND: A new propylene glycol (PG)-free 5% minoxidil (Mnx) lotion has been recently commercialized. Aim of this study was to evaluate the acceptability/tolerability and clinical efficacy of 3-month application of this new PG-free Mnx lotion and the penetration of the active compound in a reconstructed human epidermis (RHE/Episkin) model in comparison with a PG Mnx 5% lotion. METHODS: Thirty subjects of both sex with a diagnosis of AGA were enrolled in the trial. Cosmetic acceptability and clinical efficacy were evaluated after 4, 8 and 12 weeks of treatment. Global tolerability was evaluated at week 12. Cosmetic acceptability evaluation was assessed using a 7-item questionnaire using a 10-point scale score. Global Tolerability was evaluated with a 4-grade scale. Clinical efficacy was evaluated with a 5-grade scale. Skin absorption of PG-free Mnx was evaluated and compared with a PG Mnx solution using the Episkin model. RESULTS: All subjects concluded the study. The 7-item questionnaire mean values were always <2 at each time-point evaluation, demonstrating high cosmetic acceptability/tolerability. No subjects reported burning, itching or redness sensations. Global Tolerability score mean±SD value was 1.7±0.4. Clinical efficacy scores were 0.4, 0.6 and 1.2 at week 4, 8 and 12, respectively. PG-free Mnx showed similar amount of absorbed dose in comparison with PG Mnx. CONCLUSIONS: This new PG-free lotion shows a very good cosmetic acceptability/tolerability profile. Clinical efficacy was also documented. The skin penetration of this formulation is comparable to the PG Mnx lotion, supporting the bioequivalence of the two products.

Efficacy of lidocaine 7 %, tetracaine 7 % self-occlusive cream in reducing MAL-cPDT-associated pain in subjects with actinic keratosis: A randomized, single-blind, vehicle-controlled trial (The "3P-Trial").

INTRODUCTION: Conventional photodynamic therapy (cPDT) is considered a very effective treatment of actinic keratosis (AK) lesions. However, its use is limited by the fact that this procedure could be very painful. The use of topical anesthetics such as tetracaine or lignocaine/prilocaine has shown disappointing results in term of pain reduction. A self-occlusive topical 7% lidocaine/7% tetracaine anesthetic cream (LT-C) approved by the FDA to provide local topical anesthesia in adults undergoing superficial dermatological procedures is available. There are no data regarding its pain reducing effect during cPDT. We perform a prospective, randomized, single-blind, two-center trial (The 3P-Trial) to assess the pain reduction effect of LT-C versus vehicle in subjects with AK undergoing cPDT. MATERIAL AND METHODS: Fifty AK subjects (74 ± 10 years, 32 men, 18 women) with on average 17 lesions were enrolled after their written informed consent. Eight subjects presented also a total of 16 basal cell carcinoma lesions. Twenty-five were randomized to LT-cream, applied 1 h before the Methyl amino levulinate (MAL)-cPDT session and 25 to cream vehicle. The main outcome was the patient-assessed evaluation of pain score during and just after the conclusion of cPDT session (mean of the two values) using a 10-point visual analog scale (VAS). The cPDT session (LED Red light 630 nm) was performed with a duration of 6 ± 2 min with a standard fluence of 37 J/cm2. All treated lesions were prepared by gentle superficial curettage. RESULTS: All the randomized subjects concluded the trial. The mean ± SD of VAS score in vehicle group was 6.2 ± 2.7 (95 % CI of the mean: 5.0-7.5). In the group treated with LT-cream the VAS score was 3.3 ± 1.9 (95 % CI of the mean: 2.5-4.1). The active cream reduced the VAS score by 47 %. Median values of pain VAS score in the active group was reduced by 60 % in comparison with vehicle group (3.0 vs 7.5). The difference between the two groups was statistically significant (p = 0.0009; Mann-Whitney test). DISCUSSION: The 3P-trial has demonstrated that the preventive application of the self-occlusive lidocaine 7%-tetracaine 7% cream is very effective in reducing the procedure-associated pain during MAL-cPDT for the treatment of AK lesions.

Efficacy of a Topical Product Containing Purified Omental Lipids and Three Anti-Itching Compounds in the Treatment of Chronic Pruritus/Prurigo Nodularis in Elderly Subjects: A Prospective, Assessor-Blinded, 4-Week Trial with Transepidermal Water Loss and Optical Coherence Tomography Assessments.

PURPOSE: To investigate the efficacy of a cream containing purified omental lipids 10% and three anti-itching substances (polidocanol/stimutex/palmitoylethanolamine) in elderly subjects with chronic pruritus/prurigo nodularis (CP/CPN). PATIENTS AND METHODS: Thirty-five subjects (6 men; mean age 67±4 years) with CP/CPN were enrolled in a prospective, assessor-blinded, 4-week study. The cream was applied twice daily in the most affected body area. The primary endpoints were the evolution of the 10-cm visual analogue itch severity scale (VAS) and the 4-point verbal itching rating scale (VRS) (from 0 to 3). Secondary endpoints were the evolution of optical coherence tomography (OTC) of four skin parameters (acanthosis/hyperkeratosis/scale/dermal vascular pattern), assessed in a target lesioned area, and the transepidermal water loss (TEWL). Study endpoints were evaluated at baseline and after 2 and 4 weeks by an investigator unaware of the type of treatment. RESULTS: All the enrolled subjects concluded the trial. At baseline, the mean±SD scores for VAS and VRS were 4.9±2.2 and 1.7±0.7, respectively. The treatment was associated with a significant reduction (p=0.0001) of VAS score of 60% at week 2 and of 86% at week 4. VRS score was significantly reduced by 49% after 2 weeks and by 81% after 4 weeks, in comparison with baseline. TEWL (expressed as g/m2/h) mean values were 18±5.4 at baseline and 12.7±4.4 at week 2 and 9.8±4.7 at week 4 (P=0.0001 vs baseline). All the OCT parameters evaluated improved during active treatment; acanthosis grade was 0.22 mm at baseline, 0.19 mm at week 2 and 0.17 mm at week 4 (p=0.0005), representing a 23% reduction in comparison with baseline. The product was very well tolerated. CONCLUSION: This purified omental lipid with three anti-itching components cream reduces significantly itch intensity in subjects with chronic pruritus/prurigo nodularis, improving the skin barrier function and skin structure. TRIAL NUMBER: ISRCTN869561669.

Efficacy and Tolerability of Topical Polyphenon E in Multiple "Seborrheic Keratosis-Like" Lesions of the Groin in an Immunocompetent 26-Year-Old Man.

Polyphenon E 10%, a green tea extract containing epigallocatechin gallate (EGCG) as the main active compound, is a topical formulation indicated for the treatment of genital warts. Polyphenon E has also shown to be very effective in the treatment of periungual and plane warts. Here, we report a dramatic clinical effect of topical treatment with polyphenon E in a subject with multiple "seborrheic keratosis-like" lesions of the genital area. An immunocompetent 26-year-old Caucasian man came to our attention in October 2018. The subject, a regular blood donor, presented several (more than 100) light brown dome-shaped papular lesions in the groin area and in the penile shaft. A clinical diagnosis of Bowenoid papulosis-like multiple condylomata of the groin was made. A 2-month imiquimod treatment did not induce any relevant improvement in terms of volume and number of lesions. A treatment with Polyphenon E, a topical green tea extract with 10% of EGCG (Veregen®), was therefore started. After 2 months of Polyphenon E treatment, a dramatic reduction of the majority of the lesions was observed. After 3 months of treatment, all the lesions disappeared with only hyperchromic residues. Histological and immunohistological findings supported seborrheic keratosis as the conclusive diagnosis. This case report suggests that topical green tea extract could be very effective in the treatment of "seborrheic keratosis-like" lesions of the inguinal area.

Treatment of brittle nail with a hydroxypropyl chitosan-based lacquer, alone or in combination with oral biotin: A randomized, assessor-blinded trial.

We evaluated in a randomized, assessor-blinded, study the efficacy of a hydroxypropyl chitosan-based nail lacquer (HPC-NL) alone or in combination with oral biotin (HPC-NL + B) in the treatment of brittle nail syndrome (BNS). Fifty subjects (21 men; mean age 64 years) with BNS were enrolled. Twenty-six were randomly assigned to HPC-NL and 24 to the HPC-NL and biotin, 10 mg/daily (+B). Topical and oral treatments lasted for 4 consecutive months. The primary outcome was the evolution of the Onychodystrophy Global Severity Score (OGSS) assessing nail dystrophy, lamellar and longitudinal splitting, dyschromia, and pitting. At baseline, the OGSS, mean (SD), was 8.4 (2.1) in the HPC-NL group and 11.8 (2.3) in the HPC-NL + B group. The OGSS was significantly reduced during treatments in both groups. At Month 4, OGSS was reduced by 57% (HPC-NL) and 62% (HPC-NL + B). At the end of study period, the percentage of subjects with an OGSS reduction of ≥50% in comparison with baseline was 53% in the HPC-NL group and 80% in the HPC-NL + B group (p = .05). Both treatments were well tolerated. In subjects with BNS, HPC-NL alone is associated with a clinically relevant improvement of nail appearance. The combination of HPC-NL and oral biotin is associated with further clinical improvement.

Effects of topical piroxicam and sun filters in actinic keratosis evolution and field cancerization: a two-center, assessor-blinded, clinical, confocal microscopy and dermoscopy evaluation trial.

Background: Actinic keratosis (AK) is considered an "in situ" non-melanoma skin cancer induced by ultraviolet chronic exposure. Sunscreen and topical anti-inflammatory agents like diclofenac could improve the evolution of this kind of lesions. A topical product containing piroxicam 0.8% and sun filters (50 SPF) (ACTX) has been shown to be very effective in reducing AK lesions. So far, no data are available regarding the effects of this product on skin modifications evaluated by reflectance confocal microscopy (RCM) and dermoscopy at the lesion sites and on the skin around the lesions (field cancerization). Study aim: To evaluate in a two-center, assessor-blinded, prospective trial the effect of ACTX on AK number, RCM and dermoscopy parameter evolution of a target lesion in subjects with multiple AK lesions. Subjects and methods: A total of 54 subjects (42 men and 12 women; mean age 65 years) with AK lesions grade I-III located on the scalp (n = 36) or face (n = 18) were enrolled after their written informed consent. ACTX was applied twice daily on the face and scalp for six consecutive months. AK lesion count was performed at baseline and after 3 and 6 months. Lesion count was assessed in a blind fashion evaluating digital color high definition images performed at each visit and coded in a blinded fashion. RCM evaluations were performed at the same time-points. A dermoscopy evaluation was performed at baseline and after 6 months. RCM and dermoscopy were assessed on a pre-specified target lesion. The RCM severity score was used evaluating 11 items, examining stratum corneum, stratum granulosum, stratum spinous and dermal layers (maximum score 11 points). The dermoscopy score evaluated erythema, scaling and follicular plugs (from 0 to 4 for each item) and pigmentation (from 0 to 5). Results: Forty-nine subjects (90%) concluded the trial. At baseline, the mean (SD) number of AK lesions was 9.6 (5.2). AK lesions significantly decreased to 5.9 and to 5.6 after 3 and 6 months of ACTX treatment (p = .001; intention to treat analysis), representing a -42% reduction. A reduction of AK lesion numbers >50% in comparison with baseline was observed in 51% of subjects at month 6. New AK lesions appeared in five subjects (9%). The RCM mean (SD) severity score at baseline was 6.4 (2.0). ACTX treatment was associated with a progressive and significant (p = .002) reduction to 4.9 after 3 months and to 4.8 (2.3) at month 6 (a -25% reduction). The dermoscopy score at baseline was 5.5 (2) and it was reduced significantly (p = .007) to 4.5 (2) at the end of the study. The product was in general very well tolerated. Conclusion: A 6 month application of ACTX in subjects with AK lesions was associated with an improvement in AK lesion count and with a reduction in the RCM/dermoscopy severity scores of the target lesion. Trial registration number: ISRCTN22070974.

Skin protective effects of an antipollution, antioxidant serum containing Deschampsia antartica extract, ferulic acid and vitamin C: a controlled single-blind, prospective trial in women living in urbanized, high air pollution area.

Introduction: Air pollution causes skin damage and favors skin aging processes such as dark spots and wrinkles, through oxidative stress. Pollutant substances accelerate skin aging through a specific activation of intracellular receptors called AhR (aryl-hydrocarbon receptors). Deschampsia antartica aqueous extract (DAE) has shown to counteract the pollutant-induced AhR activation. Ferulic acid (FA) and vitamin C (VC) are potent antioxidant substances. A serum containing DAE/FA/VC has been recently developed. So far, no clinical data are available regarding the protective actions of this serum against the detrimental effects of air pollution on the skin. Objective: We conducted a prospective, single-blind, 28-day study to assess efficacy and protective effects against air pollution skin damage of a new serum containing Deschampsia antartica extract. Materials and methods: Twenty, photo type I-III, women (mean age 42 years) with at least three dark spots on the face, living in a homogenous urbanized, high pollution area (Rome) were evaluated. The objectives of the study were to evaluate the effects of treatment on skin barrier function, assessed by transepidermal water loss (TEWL) measurement (Tewameter), the effect on dark spots, evaluated by means of colorimetry (Colorimeter CL 400), and the effect on squalene peroxide (SQOOH)/squalene (SQ) skin ratio assessed with face swabs. Results: The trial was conducted between November 20 and December 19, 2018. In comparison with baseline, the product induced a significant improvement of skin hydration (-19% of TEWL), a significant improvement of dark spots (+7%) and a significant improvement of SQOOH/SQ ratio (-16%). The product was evaluated very well by >90% of the treated subjects regarding cosmetic acceptability. Discussion: A serum containing DAE/FA/VC has shown to improve skin barrier function, to reduce dark spots and to counteract the skin oxidative stress in women living in high pollution urban area.

Effects of a cream containing 5% hyaluronic acid mixed with a bacterial-wall-derived glycoprotein, glycyrretinic acid, piroctone olamine and climbazole on signs, symptoms and skin bacterial microbiota in subjects with seborrheic dermatitis of the face.

Objective: A new cream formulation containing hyaluronic acid 5%, complexed with a mix of a bacterial-wall-derived glycoprotein and peptide glycan complex (EDS), has been recently developed. We evaluated in a prospective, assessor-blinded, 6-week study the efficacy and tolerability of EDS in the treatment of facial seborrheic dermatitis (SD) and the effects on skin microbiota. Subjects and methods: Seventy-five subjects (mean age 46; 60 men) with moderate-severe SD of the face were enrolled. EDS cream was applied twice daily. The primary outcome was the evolution of the Investigator Global Assessment (IGA) score, evaluating erythema, scale/flaking, grade of seborrhea and itch. Superficial skin bacterial microbiome at baseline and after treatment was assessed, using the 16S rRNA gene methodology, in affected and non-affected face areas. Local tolerability was evaluated checking self-reported side effects at each visit. Results: Baseline IGA scores (mean±SD) was 10±3. The use of EDS reduced IGA score significantly by 70% at week 3 and by 88% at week 6. An increase in the abundance of Cutibacterium acnes genera associated with a significant drop of Staphylococcus genera presence was detected in affected areas. The ratio of relative abundance of genera Cutibacterium/Staphylococcus increased significantly after treatment in affected areas. The product was very well tolerated. Conclusion: Treatment with EDS applied twice daily for 6 consecutive weeks was associated with a reduction of the signs and symptoms of SD. Furthermore, after EDS cream treatment, a reequilibrating effect on facial skin microbiota was observed. The product was very well tolerated.