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.

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.

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.

Topical purified omental lipid formulations in the prevention of skin ulcers: a narrative review.

The omentum is a large peritoneal fold. Its main function is to protect abdominal organs, exerting a defensive action against infective agents. The tissue promotes repair after several types of injury. An extensive vascularisation is the key characteristic of this tissue and the omentum has the highest level of production and content of vascular endothelial growth factor (VEGF). A component of omentum is the lipid compound, which carries out important activities for the organism. Omentum is rich in neutral glycerides, phospholipids, glycolipids and gangliosides. Dermatological products containing purified omental lipids are commercially available and topical omental extracts have been useful in the softening, moisturising and smoothing of skin. Animal-derived omental lipids could be use in topical products with different textures (creams, fluids, emulsions and cleansers) and at different concentrations (10-25%) for the treatment of fragile skin or skin conditions causing risk of ulcer formation. This review summarises the pharmacological rationale of purified omental lipids in topical formulations for use in fragile skin conditions, the clinical efficacy data available in the scientific literature and the potential future perspectives. Efficacy of topical purified omental lipids have been demonstrated in numerous clinical controlled trials involving a total of 320 subjects. These studies demonstrated that this product helps prevent the formation of pressure ulcers (PU) in hospitalised high-risk subjects, improves wound healing process, normalises skin hydration in diabetic subjects with moderate-severe skin xerosis and improve the clinical evolution of diabetic foot. Therefore, purified omental lipid could be an effective tool for the management of fragile skin and the skin at high risk of PU formation.

Protective effects of Polypodium leucotomos extract against UVB-induced damage in a model of reconstructed human epidermis.

BACKGROUND: Polypodium leucotomos (PL) exerts potent antioxidant, photo-protective, and immune-modulatory activities. A reconstructed human epidermis (RHE) (Episkin) is a suitable model for the evaluation of acute UV-induced cell damage. No data regarding the photo-protective action of PL in this model are available. PURPOSE: We evaluated the effects of PL on the prevention of UVB-induced cell damage assessing sunburn cells, CPD formation, p53, Ki-67, p21 expression, and epidermal growth factor (EGF) production. MATERIALS & METHODS: RHE was incubated in standard conditions. PL was topically applied at the concentration of 2 mg/cm2 , immediately before UVB exposition. UVB exposition (300 mJ/cm2 ) was performed using a dedicated UVB lamp. Irradiated samples without PL and non-irradiated samples were used as positive and negative controls. Expression of p53, p21, and Ki-67 was evaluated with immune-histochemical methods. CPD were measured using a monoclonal antibody. RESULTS: PL significantly reduced sunburned cells (-80%) in comparison with positive control. PL significantly prevented the increase in EGF production at tested times. PL significantly reduced the p53 (-80%), p21 (-84%), and Ki-67 (-48%) positive cells. Finally, PL prevented the formation of CPD (0% vs. 20% positive cells). CONCLUSION: In this model, PL has shown to prevent UVB cell damage, the upregulation of proliferating proteins, and fully blocking the formation of CPD.

Numerical analysis of an entire ceramic kiln under actual operating conditions for the energy efficiency improvement.

The paper focuses on the analysis of an industrial ceramic kiln in order to improve the energy efficiency and thus the fuel consumption and the corresponding carbon dioxide emissions. A lumped and distributed parameter model of the entire system is constructed to simulate the performance of the kiln under actual operating conditions. The model is able to predict accurately the temperature distribution along the different modules of the kiln and the operation of the many natural gas burners employed to provide the required thermal power. Furthermore, the temperature of the tiles is also simulated so that the quality of the final product can be addressed by the modelling. Numerical results are validated against experimental measurements carried out on a real ceramic kiln during regular production operations. The developed numerical model demonstrates to be an efficient tool for the investigation of different design solutions for the kiln's components. In addition, a number of control strategies for the system working conditions can be simulated and compared in order to define the best trade off in terms of fuel consumption and product quality. In particular, the paper analyzes the effect of a new burner type characterized by internal heat recovery capability aimed at improving the energy efficiency of the ceramic kiln. The fuel saving and the relating reduction of carbon dioxide emissions resulted in the order of 10% when compared to the standard burner.

A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor blinded trial.

BACKGROUND: Atopic dermatitis (AD) is a very common chronic inflammatory and eczematous skin condition characterized by flares and remissions. Skin barrier alteration or dysfunction is the most relevant patogenetic factor. Topical corticosteroids are the mainstay treatment of AD, especially during flare periods. The daily use of emollients and moisturizers is also considered a relevant adjunctive strategy to improve skin barrier function and skin appearance in AD patients. Long-term use of topical corticosteroids is associated with important drawbacks and side effects. A corticosteroid-free cream containing starch, glycyrretinic acid, zinc oxide and bisabolol (Dermamid™; Difa Cooper, Caronno Pertusella, Varese, Italy) has been designed for the treatment of acute eczematous conditions like diaper dermatitis. However, this formulation could be particularly suitable also for AD. We evaluated in a three-center, assessor-blinded prospective 6-week treatment trial the efficacy and tolerability of this cream in children with chronic mild-to-moderate atopic dermatitis. METHODS: A total of 30 children (mean age 5 years, 18 males and 12 females) with chronic mild to moderate AD, affecting face, lower and upper limbs or trunk, were enrolled after parents' written informed consent. Exclusion criteria were a condition of immunosuppression, acute flares or a positive history of allergy to one of the components of the cream. The primary outcome was the evolution total eczema severity score (TESS) calculated as the sum of the single eczema severity score for each body area involved. Single area Eczema Severity Score (ESS) was calculated assessing eczema, infiltration, lichenification and scraching lesions using a 4-point scale grade (with 0=no sign, and 4=severe sign). A secondary endpoint was the percentage of subjects reaching at least 50% of TESS reduction at week 6 in comparison with baseline. The TESS was evaluated at baseline and after 3 and 6 weeks of treatment (twice daily application) in an assessor-blind fashion. RESULTS: At baseline the mean (SD) TESS was 11.6 (4.7). TESS was reduced significantly (P=0.0001) to 5.7 (3) after 3 weeks (-51%), and to 3.0 (2.3) at week 6 (-74%). Similar reductions were observed for single area ESS values. The percentage of subjects with at least a >50% reduction of TESS value at the end of the study was 87%. The product was very well tolerated. Only for one patient a mild burning sensation at the application site was reported. All the subjects concluded the trial. CONCLUSIONS: This trial supports the efficacy and the tolerability of a corticosteroid-free cream containing starch, glycyrretinic acid and bisabolol in the treatment of chronic mild to moderate atopic dermatitis in children.

Adherence to drug treatments and adjuvant barrier repair therapies are key factors for clinical improvement in mild to moderate acne: the ACTUO observational prospective multicenter cohort trial in 643 patients.

BACKGROUND: In acne, several studies report a poor adherence to treatments. We evaluate, in a real-life setting conditions, the impact of compliance to physician's instructions, recommendations and adherence to the treatments on clinical outcome in patients with mild to moderate acne in an observational, non-interventional prospective study carried out in 72 Dermatologic Services in Spain (ACTUO Trial). METHODS: Six-hundred-forty-three subjects were enrolled and 566 patients (88 %) completed the 3 study visits. Study aimed to evaluate the impact of adherence (assessed with ECOB scale) on clinical outcome, as well as how the use of specific adjuvant treatments (facial cleansing, emollient, moisturizing and lenitive specific topical products) influences treatment's adherence and acne severity (0-5 points score). Recommendation of specific adjuvant skin barrier repair products was made in 85.2 %. RESULTS: Overall, clinical improvement was observed throughout follow-up visits with an increased proportion of patients who reported reductions of ≥50 % on the total number of lesions (2 months: 25.2 %; 3 months: 57.6 %) and reductions of severity scores (2.5, 2.0 and 1.3 at 1, 2 and 3 months after treatment, respectively). Adherence to treatment was associated with a significant reduction on severity grading, a lower number of lesions and a higher proportion of patients with ≥50 % improvement. CONCLUSIONS: Good adherence to medication plus adherence to adjuvants was significantly associated with a higher clinical improvement unlike those that despite adherence with medication had a low adherence to adjuvants. A good adherence to adjuvant treatment was associated with improved adherence and better treatment outcomes in mild to moderate acne patients. (ISRCTN Registry: ISRCTN14257026).

Local rhamnosoft, ceramides and L-isoleucine in atopic eczema: a randomized, placebo controlled trial.

BACKGROUND: A non-steroidal, anti-inflammatory moisturizing cream containing rhamnosoft, ceramides, and L-isoleucine (ILE) (pro-AMP cream) has been recently developed for the specific treatment of atopic eczema (AE) of the face. In this trial, we evaluated the clinical efficacy and tolerability of pro-AMP cream in the treatment of facial AE in children in comparison with an emollient cream. METHODS: In a randomized, prospective, assessor-blinded, parallel groups (2:1) controlled trial, 107 children (72 allocated to pro-AMP cream and 35 allocated to control group) with mild-to-moderate chronic AE of the face were enrolled. Treatments were applied twice daily for a 6-week period. Facial Eczema Severity Score (ESS) was evaluated at baseline, week 3, and week 6, by an assessor unaware of treatment allocation. Investigator's Global Assessment (IGA) score was assessed at week 3 and at week 6. Tolerability was evaluated at week 3 and at week 6 using a4-point score (from 0: low tolerability to 3: very good tolerability). RESULTS: At baseline ESS, mean (SD) was 6.1 (2.4) in the pro-AMP cream group and 5.3 (3) in the control group. In the pro-AMP group, in comparison with baseline, ESS was significantly reduced to 2.5 (-59%) after 3 wks and to 1.0 (-84%) at week 6 (p = 0.0001). In the control group, ESS was reduced to 3 (-42%) at week 2 and to 2.6(-50%) at week 6. At week 6, ESS in pro-AMP cream was significantly lower than the control group (1.0 vs. 2.6; p = 0.001). Both products were well tolerated. CONCLUSION: Pro-AMP cream has shown to be effective in the treatment of mild-to moderate chronic lesion of AE of the face. Clinical efficacy was greater in comparison with an emollient cream. ( CLINICAL TRIAL REGISTRY: NTR4084).

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.

An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN) shows greater efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic patients in comparison with glycerol-based emollient cream. A randomized, assessor-blinded, controlled trial.

BACKGROUND: Xerosis is a common skin disorder frequently observed in diabetic patients. An effective hydration of foot skin in diabetics is a relevant preventive strategy in order to maintain a healthy foot. Urea is considered an effective hydrating and emollient topical product. The aim of the present study was to evaluate the efficacy of topical urea 5% with arginine and carnosine (Ureadin Rx Db, ISDIN Spain) (UC) in comparison with glycerol-based emollient topical product (Dexeryl, Pierre Fabre) (EC), in Type 2 diabetic patients. METHODS: We assessed the effect of UC on skin hydration in a randomized, evaluator-blinded comparative study in 40 type II diabetic patients, aged 40-75 years, treated with UC or the comparator for 28 days with a twice-daily application. The principal outcomes were the Dryness Area Severity Index (DASI) Score and the Visual Analogue Score (VAS) for skin dryness evaluated at baseline and at the end of study period by an investigator unaware of treatment allocation. RESULTS: UC induced significantly greater hydration than EC with an 89% reduction in DASI score (from 1.6 to 0.2; p < 0.001) in comparison with baseline values. After 4 weeks, compared with the control group, DASI score in UC treated group was significantly lower (0.2 vs. 1.0; p = 0.048). VAS score (high values mean better hydration) significantly increased in both groups during treatment. VAS score at the end of treatment period was significantly higher in UC group in comparison with EC group (9.8 vs. 8.2; p = 0.05). CONCLUSION: Application of urea 5%, arginine and carnosine cream increases skin hydration and alleviates the condition of skin dryness in Type 2 diabetic patients in comparison with a control glycerol-based emollient product. (Dutch Trials Register trial number 3328).

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.

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.

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.

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.

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.