High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study.

Purpose: Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers. Patients and methods: We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data. Results: Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology (p < 0.05), Clark IV and V levels (p < 0.05), vascular invasion (p < 0.05), and biological mutants (p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration (p < 0.02) and the BRAF V600E mutation (p < 0.02). Conclusion: CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis.

Natural language processing in dermatology: A systematic literature review and state of the art.

BACKGROUND: Natural Language Processing (NLP) is a field of both computational linguistics and artificial intelligence (AI) dedicated to analysis and interpretation of human language. OBJECTIVES: This systematic review aims at exploring all the possible applications of NLP techniques in the dermatological setting. METHODS: Extensive search on 'natural language processing' and 'dermatology' was performed on MEDLINE and Scopus electronic databases. Only journal articles with full text electronically available and English translation were considered. The PICO (Population, Intervention or exposure, Comparison, Outcome) algorithm was applied to our study protocol. RESULTS: Natural Language Processing (NLP) techniques have been utilized across various dermatological domains, including atopic dermatitis, acne/rosacea, skin infections, non-melanoma skin cancers (NMSCs), melanoma and skincare. There is versatility of NLP in data extraction from diverse sources such as electronic health records (EHRs), social media platforms and online forums. We found extensive utilization of NLP techniques across diverse dermatological domains, showcasing its potential in extracting valuable insights from various sources and informing diagnosis, treatment optimization, patient preferences and unmet needs in dermatological research and clinical practice. CONCLUSIONS: While NLP shows promise in enhancing dermatological research and clinical practice, challenges such as data quality, ambiguity, lack of standardization and privacy concerns necessitate careful consideration. Collaborative efforts between dermatologists, data scientists and ethicists are essential for addressing these challenges and maximizing the potential of NLP in dermatology.

Association between Vitamin D Receptor Polymorphisms, Tight Junction Proteins and Clinical Features of Adult Patients with Atopic Dermatitis.

INTRODUCTION: Few studies have explored the intricate connections between vitamin D receptor (VDR) gene polymorphisms, VDR, tight junction (TJ) protein expression and clinical features of atopic dermatitis (AD). METHODS: From 43 adult AD patients, VDR polymorphisms were genotyped from peripheral blood samples using polymerase chain reaction-restriction fragment length polymorphism. VDR, occludin, claudin-1 and ZO-1 protein expression from skin lesion biopsies were assessed by immunohistochemistry. RESULTS: The A1012G heterozygous VDR polymorphism exhibited a lower odds ratio (OR) for juvenile AD onset (OR: 0.046, 95% CI 0.004-0.51, p=0.012). In contrast, the presence of ≥2 homozygous VDR polymorphisms were significantly associated with positive skin prick test (SPT) (10/20, 50%) vs. negative SPT (1/23, 4.3%; p=0.0003). The most highly expressed TJ proteins in lesions of AD patients were claudin-1 and zonulin-1 (ZO-1), while VDR and occludin were less prevalent. A significant correlation was observed between ZO-1 expression and a body mass index ≥30 kg/m2 (OR: 12.1, 95% CI 1.06-137.9, p=0.045). Claudin-1 expression was associated with a positive SPT (OR: 8.23, 95% CI 1.04-65.5, p=0.046) and serum 25(OH)D levels were negatively correlated with ZO-1 expression (rho= -0.43, p=0.0058). CONCLUSION: This study provides novel insights into the relationship between VDR gene polymorphisms, VDR, TJ protein expression, and clinical features in adult AD patients, highlighting a significant role of vitamin D in the pathophysiology of this disease.

Interleukin-13 Inhibitors in the Treatment of Atopic Dermatitis: The Role of Tralokinumab.

INTRODUCTION: The advent of biotechnological drugs has significantly changed the management of atopic dermatitis (AD) and the approach to the moderate-to-severe form of this chronic relapsing disease. OBJECTIVES: The aim of our review is to summarize the current literature on anti-interleukin (IL)-13 in atopic dermatitis. METHODS: A literature search was organized and a systematic review was performed to summarize the most recent evidence supporting the efficacy and safety of tralokinumab. RESULTS: Tralokinumab (anti-IL-13) 300 mg every 2 weeks subcutaneously has proven effective in several clinical trials in adults and adolescents with moderate to severe atopic dermatitis inadequately controlled with other topical or systemic therapies. Tralokinumab was found to be significantly superior in terms of efficacy in reducing Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI) -75, Numeric Pain Rating Scale (NRS) pruritus, and Dermatology Life Quality Index (DLQI) scale numbers. During follow-up, tralokinumab was well tolerated with limited severity of adverse events. CONCLUSIONS: Tralokinumab leads to statistically significant improvements in disease severity and outcome scores. It represents an effective treatment option for adults with moderate to severe AD, but further large-scale studies are needed to verify long-term superiority over other treatments.

Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate-to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region.

INTRODUCTION: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. OBJECTIVES: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. METHODS: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant'Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell'Immacolata - IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. RESULTS: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Dermatology Life Quality Index score. CONCLUSIONS: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported.

Photoprotection: Current developments and controversies.

This review aimed at summarizing some of the key points that were discussed during the photoprotection session at the International Forum of Dermatology in 2022. This international conference was designed to address prominent topics of clinical dermatology in a holistic way, allowing to articulate multiple viewpoints. Therefore, this review does not claim to be exhaustive, but is instead intended to give an overview of recent developments and ongoing controversies in the field of photoprotection. Cumulative ultraviolet radiation (UVR) exposure is the major aetiological factor in the development of photoageing, photoimunosuppression and photocarcinogenesis. UVA (320-400 nm) penetrates into the dermis and damages DNA and other intracellular and acellular targets primarily by generating reactive oxygen species (ROS). It is the major contributor to photoageing, characterized by fine and coarse wrinkles, dyspigmentation and loss of elasticity. UVB (290-320 nm) is responsible for sunburns through direct damage to DNA by the formation of 6-4 cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts. Both UVA and UVB exposure increase the risk of basal cell carcinoma, squamous cell carcinoma and melanoma. In recent years, visible light (VL; 400-700 nm) has also been implicated in the exacerbation of conditions aggravated by sun exposure such as hyperpigmentation and melasma. Photoprotection is a critical health strategy to reduce the deleterious effects of UVR and VL. Comprehensive photoprotection strategies include staying in the shade when outdoors, wearing photoprotective clothing including a wide-brimmed hat, and sunglasses, and the use of sunscreen. Due to the absorption of UV filters, the safety of sunscreens has been questioned. Newer sunscreens are becoming available with filters with absorption even beyond the UV spectrum, offering enhanced protection compared with older products. Prevention of photocarcinogenesis, sun-induced or sunlight-exacerbated hyperpigmentary conditions and drug-induced photosensitivity is an important reason for adopting comprehensive photoprotection strategies.

OPT-In; Optimized Patient Treatment Outcomes in Plaque Psoriasis: A 3-Year State-Transition Treatment-Sequencing Model in the Italian Setting.

INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.

INTRODUCTION: Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs). OBJECTIVES: The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC. METHODS: Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement. RESULTS: The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724). CONCLUSIONS: The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.

Clinical and Ultrasound Efficacy of Topical Hypertonic Cream (Jovita Osmocell®) in the Treatment of Cellulite: A Prospective, Monocentric, Double-Blind, Placebo-Controlled Study.

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product's pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction.

From Cellulite to Post-liposuction Skin Irregularities: A Proposal for Definition and Classification.

Background: Post-liposuction skin irregularities (PLSI) represent a complication of liposuction, even though literature does not report specific data on their characteristics. Objective: Considering the expanding request of treatment of PLSI and their similarities to cellulite, the aim of this study is to provide a definition or classification of their appearance according to a previously described cellulite scale and to highlight eventual novel features, in patients undergoing previous liposuction and a control group. Methods: A total of 47 women, of which 47 percent performed a previous liposuction, were included in this study. Pictures of gluteal area and postero-lateral thighs were analyzed according to number and depth of depressions, skin laxity, asymmetry and v-sign by three investigators. The correlation between parameters and previous liposuction was explored with statistical analysis. Results: Our results show good to excellent intraobserver agreement and moderate to good agreement between the evaluators. Additionally, we showed that PLSI can appear as marked cellulite signs (depth of evident depression) or as specific previously not reported features including asymmetry and v-sign. Conclusion: Our findings provide information about the previously unreported morphology of PLSI. Further studies will apply validated features of PLSI proposed herein to clinical practice.

Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.