Aquaporin 1, Aquaporin 8, and Aquaporin 9 Expressions in Malignant Melanoma: A Possible Correlation with Prognosis and Clinical Outcome.

Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.

A prospective randomized controlled trial of Psychodermatology on the efficacy of Rilastil Difesa Sterile® cream in the hand eczema of healthcare workers during the COVID-19 pandemic.

Hand eczema is one of the most frequent dermatological diseases, with an incidence increased during the COVID-19 pandemic. The impact on life quality is considerable, giving rise to the need for a psycho-dermatological approach. This is a Randomized Control Trial (RCT) evaluating, either by the dermatological or psychological point of view, the effectiveness of an emollient and rehydrating topical product (Rilastil Difesa Sterile® cream) versus a standard treatment (i.e. moisturizing basic cream) in a group of 51 healthcare workers suffering from hand eczema during the COVID-19 pandemic. The enrolled subjects were randomized into a treatment or a control arm, treated for 8 weeks, and monitored through a clinical score (HECSI) and questionnaires evaluating the impact of the pathology and treatment on quality of life (DLQI and QOLHEQ). A psychometric evaluation was performed using the SCL-90 R, OCI-R, and CPDI scales. Our data, despite not reaching the statistical significance, demonstrated that both the clinical and psychological scores decreased mostly in patients treated with Rilastil Difesa Sterile® cream when compared to those treated with simple topical emollients. Moreover, we observed a high level of psychic suffering in dermatological patients and a parallel change in dermatological and psychological indicators, thus confirming their connection.

Prevalence of Self-Reported Hand Eczema Signs among Healthcare Workers after the Third Wave of COVID-19 Pandemic: A Survey in a Northern Italy Hospital.

Background: Proper hand hygiene is one of the enhanced preventive measures immediately proposed to avoid the spreading of the severe acute respiratory syndrome coronavirus-2, also known as COVID-19. Objectives: The objective of this study was to estimate the prevalence of self-reported hand eczema signs and symptoms among healthcare workers in a Northern Italy University Hospital after the third wave of the COVID-19 pandemic. Materials and methods: A cross-sectional study was conducted in June 2021. The hospital workers were invited to complete an online questionnaire through a link sent via institutional e-mail to both health personnel and support staff. Results: Eight-hundred and sixty-three subjects completed the questionnaire; 51.1% of them self-reported suffering from at least one hand skin lesion. One-hundred thirty-seven responders declared that they changed their hand hygiene habits, and 88.9% of them carried out these modifications both in occupational and domestic environments. In detail, a change in terms of daily hand washing frequency is reported as follows: before the COVID-19 pandemic, only 27.8% and 10.1% of responders washed their hands 10-20 and 20+ times per day, respectively, while after the pandemic, the percentage increased to 37.8% and 45.8%, respectively. When comparing the health care workers with the administrative staff, we observed a statistically significative difference (p = 0.0001) in the daily hand washing frequency among the two groups, with a higher value in health care personnel. Accordingly, a higher prevalence of hand eczema signs (52.8% versus 45.6%) was detected in the healthcare group. Conclusions: We underline the potential role of the pandemic in the spread of hand eczema as an occupational disease and the need to implement its prevention.

Temporal correlation between the first melanoma and the first noncutaneous tumor in CKDN2A genotyped patients.

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

COVID-19 first lockdown and outpatient hospital setting: a single center, real life study focusing on pattern changes in patients' ethnicities and treated dermatoses.

BACKGROUND: During the first Italian lockdown period, the imponent amount of hospital COVID-19 patients forced the healthcare system to re-organize visits but no information are available on outpatient ethnical patterns. Here we evaluated healthcare management changes on dermatological outpatient non-surgical settings visits during the SARS-CoV-2 pandemic. METHODS: In this retrospective study we collected data of scheduled, performed and not-performed visits, together with patients' characteristics (i.e., age, gender) with a particular attention for ethnicities among the outpatients accessing during the first Italian lockdown (March 5-April 30, 2020). Then, we compared these data with the corresponding ones in 2019 (before COVID-19 pandemic). RESULTS: During the Italian lockdown the dermatological department registered a great decrement (-83.5%, P<0.001) in visits compared to the corresponding time period in 2019. Performed and scheduled visits to non-oncological stable patients together with emergency accesses to dermatology decreased. Non-Italian patients decreased accesses, especially the South East Asians (-70.4%) and North Africans (-90.0%). CONCLUSIONS: Hospitals policy and mass media deeply condition the public opinion, and this aspect may explain a different access to the hospital among non-Italian patients. Telemedicine should be promoted especially among non-Italian communities in Italy to overgo patients' skepticism and incentivize prevention and early treatment in dermatological conditions.

The impact of COVID-19 pandemics on dermatologic surgery: real-life data from the Italian Red-Zone.

BACKGROUND: The COVID-19 pandemic is challenging healthcare systems worldwide. Dermatology had to re-prioritize visits, guarantee urgent care, and ensure continuity for chronic patients. OBJECTIVES: To evaluate the COVID-19 impact on dermatologic surgery outpatient management. MATERIAL AND METHODS: In this real-life retrospective observational study, we evaluated both major and minor outpatient surgeries (MaOS and MiOS) performance in 2020, before and during the first month of lockdown declaration, in a primary referral center in Northern Italy. During the lockdown, all lifesaving and cancer surgery, (approximately 80% of our usual activities), were continued. Data from 2020 were compared with the 2019 corresponding periods to assess the real-life impact of COVID-19 in dermatologic surgical activities. RESULTS: From January 1st to April 3rd, 2020 we performed 769 interventions, compared to 908 over the corresponding 2019 period. After the lockdown, scheduled surgeries were reduced by 14.8%; overall performed ones displayed a reduction of 46.5% (51.6% MaOS, 44.2% MiOS). 52.9% and 12.5% procedures were canceled due to patients' renunciation and due to confirmed/suspected COVID-19, respectively. CONCLUSIONS: While reduced in number, dermatologic surgeries, similarly to other surgical specialties, remained operative to provide oncological and/or life-saving procedures.

Nicotinamide Attenuates UV-Induced Stress Damage in Human Primary Keratinocytes from Cancerization Fields.

UVB radiation directly damages DNA, increases ROS and nitric oxide (NO) release, and promotes inflammation leading to genomic instability and cell death. Nicotinamide (NAM) is the precursor of NAM adenine dinucleotide, essential for cell energy production and DNA damage repair. NAM protects HaCat cells from UV-induced impairment; however, little is known about its effects on human primary keratinocytes and those isolated from field cancerization (i.e., field cancerization human primary keratinocytes [FC-HPKs]). We examined the role of NAM against UV-induced oxidative stress damages in FC-HPKs, isolated from precancerous lesions and skin cancers, and in normal human epidermal keratinocytes. Cells were treated for 18, 24, and 48 hours with NAM (5, 25, and 50 µM, respectively) before UVB irradiation. FC-HPK showed four-fold higher basal ROS levels than normal human epidermal keratinocytes; NAM downregulated ROS production only in irradiated FC-HPKs, which showed a greater sensibility to UV rays. UV exposure increased OGG1, inducible nitric oxide synthase, and IL-1ß expression, an effect counteracted by NAM pretreatment. Intracellular nitric oxide production and DNA damages were inhibited by NAM exposure before irradiation. Collectively, our findings indicate that pretreatment with 25 µM NAM 24 hours before UVB irradiation effectively prevents oxidative stress formation, DNA damage, and inflammation in both normal human epidermal keratinocytes and FC-HPKs.

North Italy: Welcome to the Tropics!

We describe a case of cutaneous Larva Migrans in an 8-year-old Caucasian girl. The lesion appeared ten days after a bath in the river in a valley in the north-east of Piedmont. The patient was successfully treated with Albendazole 400 mg daily for 5 days. Autochthonous cases are rare, particularly in northern Italy. Probably the high temperatures and the high degree of humidity favored by the climate changes to which Europe is subjected are favorable to the development of larvae. The diagnosis of cutaneous Larva Migrans should, therefore, be considered also in individuals who have not traveled in geographic areas at risk for the climate.

Minced Skin Grafting: A Minimally Invasive and Low-Cost Procedure to Treat Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that usually presents as a painful ulcer with erythematous and undermined borders and is often characterized by pathergy. Although this condition precludes a surgical approach, in cases resistant to treatment with immunosuppressive agents, skin grafts and amputation are considered last resorts. Both expose the patient to the risk of developing new lesions. A minimally invasive autologous graft, "minced micrografts," is a possible alternative to speed up the healing process, reducing the risk of pathergy.This procedure was implemented in a 28-year-old man with PG who was prescribed prednisone and dapsone and who had a large ulcer on the arm and armpit that had persisted for 4 months and was undergoing slow re-epithelialization. A sample of finely minced skin previously taken from the clavicular region suspended in a hydrogel was spread on the wound bed in a proportion of less than 1:6 with respect to the receiving site. Seven days later, initial signs of re-epithelialization appeared, and the wound healed in 3 months.In patients with PG, the minced micrograft method could facilitate ulcer healing by releasing cytokines, chemokines, and growth factors, thus promoting granulation tissue formation, neoangiogenesis. Because this method does not require special equipment or complex surgical techniques and is very low cost, it should be an integral part of the arsenal of procedures aimed at improving the quality of life of patients with PG.

Safety margins for dermatofibrosarcoma protuberans: a comparison between wide local excision and Mohs Tubingen technique.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally infiltrating, rarely metastasizing, soft tissue tumour. Due to its indistinct margins, local aggressive behaviour and high recurrence rate, the surgical approach is complex. Micrographic surgery and variants of this technique, e.g. Tubingen torte technique (TTT), should be considered as first-line treatment. OBJECTIVES: To confirm that TTT is a safe and tissue-sparing technique, relative to theoretical wide local excision (WLE), for the same lesions, as recommended by the guidelines in the literature. MATERIALS AND METHODS: Seventeen patients with histologically confirmed DFSP, treated with TTT between September 2014 and February 2019, were retrospectively analysed. For each patient, the final TTT excision area was calculated and compared with the theoretical equivalent area based on WLE. The difference in area was calculated and presented as percentage difference of preserved healthy skin based on the two approaches. RESULTS: In our patients, the mean preoperative lesion size was 4.55 ± 5.34 cm2. The mean final total excised area was 17.73 ± 11.75 cm2 for TTT and 53.65 ± 15.57 cm2 for WLE. The amount of preserved healthy tissue using the micrographic technique was significant; 69.15% (95% CI: 62.95-75.36) of healthy tissue was preserved using TTT. No recurrence or metastases were observed in any of the patients after a median follow-up period of 38.00 ± 21 months. CONCLUSION: In our experience, TTT remains a safe, effective and tissue-sparing treatment for DFSP patients, especially when it is essential to spare tissue and in challenging locations.

Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers.

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.