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.

The SILVER study. Efficacy of topical nitric-zinc complex solution in the treatment of resistant warts: A postmarketing evaluation.

The treatment of cutaneous viral warts caused by human papillomavirus (HPV) infection is often subject to local recurrence and a long clinical and treatment course. Our aim was to analyze real-life data on the treatment of difficult-to-treat warts from a multicenter postmarketing surveillance assessment on the efficacy, tolerability, and safety of a commercially available nitric-zinc complex solution (NZCS). Dermatologists from 14 Italian centers completed a questionnaire about their clinical experience on treatment of "difficult-to-treat" warts, which included warts in the plantar, periungual, anogenital and aesthetically sensitive areas. The questionnaire was designed to obtain detailed information on wart treatment and compare NZCS efficacy with previous treatments. Of 106 questionnaires returned, 83 reported NZCS use; 67 had previous treatments (23 cryotherapy, 2 electrocoagulation, 12 other topical application, and 30 combined treatment, such as laser, cryotherapy, and/or electrocoagulation). NZCS had superior efficacy to that of previous treatments (p < .0001), resulting in 84.1% with a full or partial clearance (vs. 44.8% for previous treatments), and had better local tolerability (p < .0001). NZCS showed better efficacy and tolerability than other previous wart treatments.

Split-thickness skin grafting for reconstruction of auricular skin defects: a statistical analysis.

BACKGROUND AND OBJECTIVES: Surgical reconstruction following the removal of large malignant auricular lesions is challenging. While many options for defect closure have been described, in the elderly population usually affected flap surgery, long anesthesia times, patient compliance, and anticoagulant therapy pose additional risks. An alternative quick, simple, and effective method of defect closure is therefore highly desirable. The objective of the present study was to assess the aesthetic outcome, healing process, complications, and recurrence rates associated with unmeshed split-thickness skin grafts (STSGs) used for covering large auricular skin defects following cartilage-sparing skin cancer removal. PATIENTS AND METHODS: Under local tumescent anesthesia, 32 patients received STSGs for defect closure following the removal of malignant cutaneous neoplasms of the ear. RESULTS: The average defect size was 8.0 cm². In all cases, complete healing of the recipient site occurred within two weeks. There were no major complications. The aesthetic outcome was rated highly by patients as well as by the dermatosurgeon involved and two independent plastic surgeons. CONCLUSIONS: STSGs are a valid option for closing large auricular skin defects. Even large cutaneous tumors of the external ear do not necessarily infiltrate the cartilage. Thus, cartilage-sparing tumor resection with subsequent defect closure using a STSG is an excellent and quick method associated with high patient satisfaction.

Spalthauttransplantation zur Defektdeckung am Ohr: eine statistische Analyse.

HINTERGRUND UND ZIELE: Die Rekonstruktion nach Entfernung ausgedehnter maligner Hauttumoren am Ohr ist eine Herausforderung. Verschiedene Methoden der Defektdeckung wurden beschrieben. Lappenplastiken, längere Anästhesiezeiten, geringe Compliance und Antikoagulation stellen bei den oft älteren Patienten zusätzliche Risiken dar. Eine rasch, effizient und unkompliziert durchführbare Methode der Defektdeckung ist daher wünschenswert. Ziel der Studie war die Beurteilung des ästhetischen Resultats, des Heilungsprozesses, der Komplikations- und Rezidivrate nach Transplantation ungenetzter Spalthaut (SPHT) zur Defektdeckung nach knorpelerhaltender Resektion maligner Tumoren am Ohr. PATIENTEN UND METHODIK: 32 Patienten wurden nach Entfernung von Hauttumoren am Ohr einer Defektdeckung mittels SPHT unterzogen. ERGEBNISSE: Die durchschnittliche Defektgröße betrug 8,0 cm2 . Eine vollständige Einheilung des Transplantates erfolgte in allen Fällen innerhalb von zwei Wochen. Wesentliche Komplikationen traten nicht auf. Das ästhetische Resultat wurde sowohl von den Patienten als auch von einem Dermatochirurgen und zwei plastischen Chirurgen als gut bewertet. SCHLUSSFOLGERUNGEN: Die SPHT am Ohr ist eine zuverlässige Methode zur Deckung ausgedehnter Hautdefekte. Selbst bei großen Tumoren des äußeren Ohres ist der Ohrknorpel nicht immer infiltriert. Eine knorpelschonende Tumorresektion mit anschließender Defektdeckung mittels SPHT ist eine ausgezeichnete und rasch durchführbare Technik mit hoher Patientenzufriedenheit.

Epidemiology of pyoderma gangrenosum: Results from an Italian prospective multicentre study.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by painful, necrotic ulcerations. PG is described as a rare disease: the world-wide incidence is estimated to be around 3 to 10 cases per million population per year. These estimations are based mostly on case reports and retrospective case series; there are no prospective, multicentre studies on the matter. The apparent rarity of PG is in contrast with our clinical perception as dermatologists: in our opinion, PG is not so uncommon. Therefore, we decide to investigate the epidemiology of PG in the Italian population and confirm our clinical suspicions that it is not an orphan disease. We enrolled all patients diagnosed with PG in 8 Italian Dermatological Departments from 1st October 2014 to 1st November 2015, and we recorded their features. Our data, collected from 64 patients, are in accordance with those of the published literature regarding the epidemiology and features of PG. In an Italian population of roughly 8 million inhabitants of 7 provinces, we found an incidence of 5.17 new cases per million population per year. Unlike our predictions before the study, we confirmed the world-wide incidence of PG. To our knowledge, this is the first observational, multicentre study on PG. We hope that it provides a stimulus for further researches on PG and for the creation of an Italian register.

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.

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo.

Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, ß1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in Ras(G12V)-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

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).

Isolation and characterization of squamous cell carcinoma-derived stem-like cells: role in tumor formation.

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of ß1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2-4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors.

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.