IGF1 synthesis after CO2 fractional laser resurfacing (FLR): New insights in the treatment of scalp actinic keratoses

ObjectivesActinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin-like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet-induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin-like growth factor 1 (IGF-1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing. MethodsWe enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm(2), treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real-time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients. ResultsIGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow-up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four- and six-follow-up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment. DiscussionTaken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma

Therapeutic Potential of Targeting the JAK/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition

Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients' quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis

Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma

Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future

A miniaturized silicon based device for nucleic acids electrochemical detection

In this paper we describe a novel portable system for nucleic acids electrochemical detection. The core of the system is a miniaturized silicon chip composed by planar microelectrodes. The chip is embedded on PCB board for the electrical driving and reading. The counter, reference and work microelectrodes are manufactured using the VLSI technology, the material is gold for reference and counter electrodes and platinum for working electrode. The device contains also a resistor to control and measuring the temperature for PCR thermal cycling. The reaction chamber has a total volume of 20 μL. It is made in hybrid silicon–plastic technology. Each device contains four independent electrochemical cells.Results show HBV Hepatitis-B virus detection using an unspecific DNA intercalating redox probe based on metal–organic compounds. The recognition event is sensitively detected by square wave voltammetry monitoring the redox signals of the intercalator that strongly binds to the double-stranded DNA. Two approaches were here evaluated: (a) intercalation of electrochemical unspecific probe on ds-DNA on homogeneous solution (homogeneous phase); (b) grafting of DNA probes on electrode surface (solid phase).The system and the method here reported offer better advantages in term of analytical performances compared to the standard commercial optical-based real-time PCR systems, with the additional incomes of being potentially cheaper and easier to integrate in a miniaturized device. Keywords: Electrochemical detection, Real time PCR, Unspecific DNA intercalato

Preliminary Sizing of High-Altitude Airships Featuring Atmospheric Ionic Thrusters: An Initial Feasibility Assessment

When it comes to computing the values of variables defining the preliminary sizing of an airship, a few standardized approaches are available in the existing literature. However, when including a disruptive technology in the design is required, sizing procedures need to be amended, so as to be able to deal with the features of any additional novel item. This is the case of atmospheric ionic thrusters, a promising propulsive technology based on electric power, where thrusters feature no moving parts and are relatively cheap to manufacture. The present contribution proposes modifications to an existing airship design technique, originally conceived accounting for standard electro-mechanical thrusters, so as to cope with the specific features of new atmospheric ionic thrusters. After introducing this design procedure in detail, its potential is tested by showing results from feasibility studies on an example airship intended for a high-altitude mission. Concurrently, the so-obtained results allow the demonstration of the sizing features corresponding to the adoption of atmospheric ionic thrusters at the current level of technology, comparing them to what is obtained for the same mission when employing a standard electro-mechanical propulsion system

Syphilis Diagnosis and Treatment: State of The Art

The present review summarises the current knowledge in the field of syphilis diagnosis and treatment, along with epidemiologic and historical data. A literature search was conducted in PubMed and Google Scholar, using the search terms "syphilis", "diagnosis", "dermoscopy", "management AND treatment", "laboratory tests AND syphilis", and "primary OR secondary OR tertiary OR congenital syphilis". A total of 55 out of 100 papers were included in this review. An overview of the different clinical presentation of primary, secondary, tertiary, and congenital syphilis, with particular attention to dermatologic signs and dermoscopic examination, is provided. The panorama diagnostic procedures are illustrated, along with their accuracy and recommendation. Treatment and management options of patients at different syphilis stages are provided and discussed according to the referring guidelines. The dermatologist can play a key role in providing the early and correct diagnosis and setting up in the proper management of patients with syphilis infection

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-na & iuml;ve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (+/- 9.1) to 0.7 (+/- 1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term

How to integrate surgery and targeted therapy with biologics for the treatment of hidradenitis suppurativa: Delphi consensus statements from an Italian expert panel

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified ten areas of interest based on published evidence and personal experience: 1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); 2) tailoring surgery to HS characteristics; 3) wide local excision; 4) pre-surgery biologic treatment; 5) concomitant biologic and surgical treatments; 6) pre- and post-surgery management; 7) antibiotic systemic therapy; 8) biologic therapy after radical surgery; 9) management of adverse events to biologics; 10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements