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The current scientific evidence suggests that surgical navigation (SN) can contribute to improve oncologic outcomes in sinonasal and craniofacial surgery. The present study investigated the feasibility of intraoperative SN and its role in improving the outcomes of surgically treated sinonasal and craniofacial tumors. This prospective study compared navigation-guided surgery for sinonasal or craniofacial malignancies with a pair-matched cohort (1:2 matching) of patients operated without SN. A systematic review of the literature was performed. Thirty-five patients who underwent navigation-guided surgery were included. The pair-matched control cohort included 70 patients operated without SN. The margin status analysis demonstrated a lower rate of positive margins (p = 0.013) in the SN group, especially in pT4 (p = 0.034), recurrent (p = 0.024), high-grade tumors (p = 0.043), and endoscopic-assisted open surgery (p = 0.035). The mean preoperative time did not show a significant difference between surgeries performed with or without SN (1.26 vs. 1.23 h, p = 0.445). However, surgeries utilizing SN had a significantly longer median duration compared to those without (8.10 vs. 6.00 h, p = 0.029). A total of 209 patients were included in the meta-analysis; 91 patients (43.5 %) underwent surgery with SN. The results of the meta-analysis showed an improvement in terms of negative margins rate with the use of SN (OR = 2.62; 95%-confidence interval: 1.33-5.17). In conclusion, intraoperative SN can contribute to achieve a clear margin resection, especially in locally advanced tumors, recurrences, highly aggressive histologies, and when endoscopic-assisted open surgery is employed., Competing Interests: Declaration of conflicting interests As of April 2024, Dr. Marco Ferrari and Prof. Piero Nicolai are members of an advisory board on the use of steroid-eluting resorbable stents (Propel®) distributed by the same vendor of the navigation system used in the present study (Medtronic®). Other author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The introduction of adjuvant therapies for patients with resected cutaneous melanoma (CM) has increased the need for sensitive biomarkers for risk stratification and disease monitoring. This study aims to investigate the utility of circulating tumor DNA (ctDNA) assessment in predicting and reflecting disease status during adjuvant therapy., Methods: We enrolled 32 patients with resected BRAF-mutated stage III CM receiving adjuvant targeted therapy or immunotherapy. Plasma samples of patients were collected at the baseline (treatment initiation) and during the therapy, and BRAF-mutated ctDNA was quantified by droplet digital PCR (ddPCR)., Results: Baseline ctDNA was detected in 11/32 (34.4%) patients and predicted postoperative high risk of relapse [HR 3.79, 95% CI 1.20-12.00, p = 0.023]. The three-year overall survival (OS) rate was 54.6% (95% CI 22.9-77.9) versus 95% (95% CI 69.5-99.3) in ctDNA-positive and negative groups, respectively, with significantly worse OS for ctDNA-positive patients [HR 7.92, 95% CI 1.56-40.36, p = 0.013]. Among the baseline ctDNA-positive group (high-risk patients), longitudinal ctDNA detection during adjuvant therapy reflected the clinical outcomes. Only non-relapsing patients cleared their plasma ctDNA by the end of the treatment, while persistent ctDNA detection provided early evidence of disease recurrence., Conclusions: ctDNA detection shows promising results in the post-operative setting for identifying cutaneous melanoma patients at the highest risk of relapse and for real-time monitoring of patients' clinical status and treatment response., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by Comitato Etico Interaziendale AOU Città della Salute e della Scienza di Torino (TESEO − 0061280 - CE CS2/1306) and was conducted in accordance with the ethical standards of the University of Turin IRB and the principles of the declaration of Helsinki. Informed consent: Informed consent to surgical procedure and data collection was obtained from all subjects involved in the study. Competing interests: The authors declare no conflict of interest., (© 2024. The Author(s).)

Background: Psoriasis (PSO) involves about 1-3% of the population, and around 75% of women develop PSO before the age of 40. Official guidelines on the treatment of woman with anti-IL17 and anti-IL23 during this potential childbearing time are not currently available. Objective: To investigate the effectiveness and safety of biologic treatments in women of childbearing age. Methods: At the Dermatology Clinic of the University of Turin, Italy, 172 women aged 20-55 years underwent IL-17 and IL-23 inhibitor therapy for moderate-severe PSO and were followed up to 52 weeks in a real-life, retrospective, single-center study. Results: Overall, 40% of patients achieved PASI 100 at week 16, and 72% at week 52. A similar trend was observed for PASI 90 and PASI < 3 with almost 80% and 90% of patients achieving the target at 52 weeks. As for PASI 100, a statistically significant difference ( p = 0.004) was found at 16 weeks, with 23.84% of patients achieving PASI 100, with IL-17 and 15.70% with the IL-23 inhibitor. No statistically significant differences were found at 28 and 52 weeks. No statistically significant differences in PASIs at any time points were recorded across the different biologic agents. Forty-six patients discontinued treatment. The most reported side effects were headache, nausea, asthenia, injection site pain, and rhinitis. Conclusions: This study showed that biologic drugs are effective and safe in women of childbearing age, with negligible side effects.

Objectives: Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients., Methods: A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with patient-reported outcomes measures (PROMs) and nasal cytology. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤ 4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day., Results: Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction of the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in 2 cases, which led to dupilumab discontinuation., Conclusions: Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Hand eczema (HE) is a prevalent inflammatory skin condition, impacting 15-20% of individuals, with a notable incidence rate of approximately 7.3 cases per 1000 person/years. This condition exhibits significant gender-based variability, with a higher prevalence in females. The clinical presentation of HE is characterized by pruritic erythematous, edematous, weeping plaques, vesicles, and/or bullae, showcasing considerable heterogeneity., Evidence Acquisition: A literature search was conducted across multiple databases, including Medline, Pubmed, Scopus, and the Cochrane Library. The search was conducted using the following key words and medical subject heading (MeSH) terms: "hand," "eczema," "dermatitis," "dermoscopy," and "histology," employing the Boolean term "AND" to combine the research terms for optimal search precision. PRISMA algorithm has been used for article screening. The search scope included manuscripts published up to October 1, 2023., Evidence Synthesis: Up to 50% of HE cases are associated with atopic dermatitis, emphasizing the complex interplay between various dermatological conditions. Common subtypes of HE include irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), atopic hand eczema (AHE), and protein contact dermatitis/contact urticaria (PCD). The chronic nature of HE presents a substantial management challenge, often underestimated, leading to delayed treatment and potential progression to chronic hand eczema (CHE). Beyond individual health implications, HE exerts a profound impact on occupational, domestic, social, and psychological aspects, establishing itself as the most prevalent occupation-related skin disease. This paper seeks to establish a comprehensive classification system for HE, integrating clinical, dermoscopic, and histological elements. Dermoscopy, specifically, proves instrumental in distinguishing HE from palmar psoriasis, revealing characteristic features such as yellow scales and irregular vessels. Histopathological findings underscore the dynamic changes observed from acute to chronic stages, while challenges in differentiating hyperkeratotic HE from psoriasis underscore the necessity for a holistic diagnostic approach., Conclusions: Accurate diagnosis and effective management of HE necessitate a holistic perspective that recognizes the inherent complexities of this inflammatory skin disease. By providing a multidimensional classification system, incorporating clinical, dermoscopic, and histological parameters, this paper aimed to contribute to a more nuanced understanding of HE and facilitate improved approaches to its diagnosis and treatment.

This study was carried out at the Dermatologic Clinic of the University of Turin, Italy, to assess the effectiveness and safety of adjuvant therapy in patients who received either targeted therapy (TT: dabrafenib + trametinib) or immunotherapy (IT: nivolumab or pembrolizumab) for up to 12 months. A total of 163 patients participated, including 147 with stage III and 19 with stage IV with no evidence of disease. The primary outcomes were relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). At 48 months, both TT and IT approaches yielded comparable outcomes in terms of RFS (55.6-55.4%, p = 0.532), DMFS (58.2-59.8%, p = 0.761), and OS (62.4-69.5%, p = 0.889). Whilst temporary therapy suspension was more common among TT-treated patients compared to IT-treated individuals, therapy discontinuation due to adverse events occurred at comparable rates in both groups. Predictors of relapse included mitoses, lymphovascular invasion, ulceration, and positive sentinel lymph nodes. Overall, the proportion of BRAF-mutated patients receiving IT stood at 7.4%, lower than what was observed in clinical trials.

Background: Advancements in managing stage III melanoma have involved the implementation of adjuvant therapies alongside a simultaneous decrease in the utilization of completion lymph node dissection (CLND) following positive sentinel node biopsy (SLNB). Methods: This retrospective study from the University of Turin's Dermatology Clinic analyzed relapse-free survival (RFS) and overall survival (OS) among stage III melanoma patients (n = 157) who underwent CLND after positive SLNB versus those who did not receive such procedure. Results: Patients without CLND had a median RFS of 49 months (95% CI 42-NA), while CLND recipients showed 51 months (95% CI 31-NA) ( p = 0.139). The 48-month OS for non-CLND patients was 79.8% (95% CI 58.2-91.0) versus 79.2% (95% CI 67.5-87.0) for CLND recipients ( p = 0.463). Adjusted Hazard Ratios through inverse probability treatment weighting revealed the impact of CLND to be insignificant on RFS (aHR 0.90, 95% CI 0.37-2.22) and marginal on OS (aHR 0.41, 95% CI 0.13-1.21). Conversely, adjuvant therapy significantly reduced the risk of relapse (aHR 0.46, 95% CI 0.25-0.84), irrespective of CLND. Conclusions : This study corroborates the growing evidence that CLND after positive SLNB does not enhance RFS or OS, while emphasizing the crucial role of adjuvant therapy, be it immunotherapy or targeted therapy, in reducing the risk of relapse in melanoma patients with positive SLNB.

Background: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE)., Methods: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized., Results: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported., Conclusions: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes., (© 2024 Wiley Periodicals LLC.)

Background: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required., Objective: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes., Methods: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022., Results: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors., Conclusions: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research., (© 2024 European Academy of Dermatology and Venereology.)

is missing (Short communication).

Real-world data on the long-term effectiveness of the anti-IL17 agent secukinumab in treating moderate-to-severe Hidradenitis suppurativa (HS) are lacking. In this study, 24 patients with moderate-severe HS received five weekly subcutaneous injections followed by maintenance doses every 4 weeks. Primary outcomes included HiSCR, IHS4 reduction, and DLQI measures assessed at 12-week intervals. The median secukinumab drug survival was 16.0 months (range 3-51), with a 56.5% maximal response rate at 6 months and dropout exceeding 40% at 1 year. Baseline disease burden emerged as a key predictor of treatment response, overshadowing factors like sex or BMI. Prior systemic steroid use negatively impacts drug survival. The study underscores the critical 6-month window for assessing treatment efficacy, emphasizing the importance of initial induction dosing. Additionally, the newly developed scoring system, IHS4-55, showed analogies to the older HiSCR score in capturing treatment response. In this real-life scenario, challenges persist in HS management, necessitating innovative therapeutic approaches and predictive markers., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/Objectives: Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous disorder associated with various hematologic malignancies, most commonly chronic lymphocytic leukemia. Detailed clinicopathologic studies of EDHM are lacking and the pathogenesis remains enigmatic. Initially thought to be a hypersensitivity reaction to insect stings, subsequent reports have challenged this understanding. The prognostic implications of EDHM remain unclear. Methods: A retrospective clinicopathologic study was performed on patients diagnosed with EDHM. Hematologic and dermatologic data were reviewed. Histologic specimens were re-evaluated and lesions were classified into acute/subacute, fully developed, and chronic/regressing. Results: The study included 35 patients. In 80% of these patients, EDHM was diagnosed after the hematologic disorder. Approximately 45% of the cohort experienced hematologic disease progression or relapse, while 65% required therapeutic intervention during the course of their hematologic disease. In total, 15/19 CLL patients had non-mutated IgHV, a marker of a more aggressive hematologic disease course. Dermatologic lesion morphology was heterogeneous, with most lesions occurring on exposed areas, and a significant 94% of patients demonstrated lesion seasonality. Histopathologic findings were consistent with features typically associated with insect bites. In addition, examination of lesions at different chronological stages revealed substantial similarities with Wells syndrome. Conclusions: Our findings support the potential role of insect bites in triggering EDHM in the context of adaptive immune dysfunction. EDHM may be associated with a more aggressive disease course or may be a marker of disease progression. The observed co-occurrence of features typical of Wells syndrome in EDHM patients suggests that these conditions are part of a spectrum of disorders that vary in clinical expression.

Introduction: Over the past decade, significant advancements in the field of melanoma have included the introduction of a new staging system and the development of immunotherapy and targeted therapies, leading to changes in substage classification and impacting patient prognosis. Despite these strides, early detection remains paramount. The quest for dependable prognostic biomarkers is ongoing, given melanoma's unpredictable nature, especially in identifying patients at risk of relapse. Reliable biomarkers are critical for informed treatment decisions., Areas Covered: This review offers a comprehensive review of prognostic biomarkers in the context of clinical trials for immunotherapy and targeted therapy. It explores different clinical scenarios, including adjuvant, metastatic, and neo-adjuvant settings. Key findings suggest that tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors are promising biomarkers associated with improved treatment responses., Expert Opinion: Identifying practical prognostic factors for melanoma therapy is challenging due to the tumor's heterogeneity. Promising biomarkers include tumor mutational burden (TMB), circulating tumor DNA, and those characterizing the tumor microenvironment, especially the immune component. Future research should prioritize large-scale, prospective studies to validate and standardize these biomarkers, emphasizing clinical relevance and real-world applicability. Easily accessible biomarkers have the potential to enhance the precision and effectiveness of melanoma management.

Introduction: Current treatment guidelines for cutaneous T cell lymphoma (CTCL) advocate a stage-driven approach, considering clinical presentation, symptom burden, and patient comorbidities. Therapy selection hinges on factors like disease subtype, severity, and treatment availability. The primary goal is to enhance the quality of life by mitigating symptoms, as achieving lasting complete remission is infrequent., Areas Covered: Over the past decade (2013-2023), the therapeutic landscape of CTCL has experienced substantial transformation with the introduction of innovative therapies. This review explores the main pivotal developments in traditional treatment schedules and recently introduced drugs, aiming to offer clinicians and researchers a thorough perspective on the decade's progress in the field., Expert Opinion: Despite the progress made in CTCL therapeutics, ranging from topical chemotherapeutics to immunomodulatory agents, several unmet needs persist. Firstly, there is a pressing need for the incorporation of readily available predictors for treatment response, encompassing clinical, pathological, and molecular features. Secondly, a more profound comprehension of the tumor microenvironment is imperative to optimize the landscape of targetable molecules. Lastly, the undertaking of studies on combination regimens should be encouraged as it enhances therapy efficacies by synergistically combining agents with diverse modes of action.

Competing Interests: Conflicts of interest None disclosed.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin' sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment ( p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients' emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP.

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Introduction: Immunomodulating therapies harness the power of the immune system to combat disease. In advanced melanoma, immune checkpoint inhibitors have significantly improved survival outcomes by activating the immune system to recognize and eliminate cancer cells. In psoriasis, interleukin inhibitors effectively suppress inflammation and improve disease symptoms., Areas Covered: We provide a meta-opinion-based consensus paper on the analogies and differences in treatment mechanisms, duration, frequency between immunotherapy for advanced melanoma and biologics for psoriasis. Combining the current scientific evidence with expert insights, we provide valuable guidance for future research and decision-making processes., Expert Opinion: The development of immunological treatments in melanoma and psoriasis has revolutionized dermatology, but the quest for tailored therapies that maximize efficacy continues. Managing cutaneous exacerbations during melanoma immunotherapy in psoriatic patients remains challenging. Similarly, treating oncologic psoriasis patients resistant to traditional therapies requires individualized approaches. Research is needed to identify response predictors in both conditions and address the sustainability of healthcare systems due to the high cost of biologics. Drug delay studies for psoriasis and longer follow-up evaluations after immunotherapy discontinuation in melanoma are essential for optimizing treatment outcomes and resource allocation.

Purpose: The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab., Methods: This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded., Results: Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown., Conclusions: DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The facial artery perforator flap is a valuable alternative for reconstruction of small to medium defects in the central midface and provide pleasing cosmetic results, allowing reconstruction in a one-stage procedure. Since Doppler ultrasound is not applicable to distinguish perforator from source artery, anatomical studies are needed to identify perforator areas along the course of the facial artery., Methods: Twenty facial arteries of 10 fresh anatomical head specimens were dissected. All perforators with an outer diameter of at least 0.50 mm were identified and injected with dye to color their respective vascular territories. Size and location of colored skin territories as well as the location of its perforators were documented and statistically analyzed., Results: In total, 89 perforators were identified. The average number of perforators per facial artery was 4.45±1.15. The mean outer diameter of the perforator at the origin of the facial artery was 0,65±0.14 mm. The mean size of the colored skin territories was 577.57±488.81 mm 2 . Perforator diameters were significantly associated with the size of its resulting perforasomes. Furthermore, perforators mostly originated in two specific areas: 3.5 cm lateral and caudal and 4.5 cm lateral and 5.5 cm caudal of the anterior nasal spine., Conclusion: This study provides evidence of two predominant locations of emergence of facial artery perforators. Additionally, the significant correlation between perforator size and its appendant perforasomes as well as their location with reference to the anterior nasal spine as relevant osseous landmarks helps surgeons in decision making for flap design and surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: Over the past two years, the scientific community has witnessed an exponential growth in research focused on identifying prognostic biomarkers for melanoma, both in pre-clinical and clinical settings. This surge in studies reflects the need of developing effective prognostic indicators in the field of melanoma., Areas Covered: The aim of this work is to review the scientific literature on the most recent findings on the development or validation of prognostic biomarkers in melanoma, in the attempt of providing both clinicians and researchers with an updated broad synopsis of prognostic biomarkers in cutaneous melanoma., Expert Opinion: While the field of prognostic biomarkers in melanoma appears promising, there are several complexities and limitations to address. The interdependence of clinical, histological, and molecular features requires accurate classification of different biomarker families. Correlation does not imply causation, and adjustments for confounding factors are often overlooked. In this scenario, large-scale studies based on high-quality clinical trial data can provide more reliable evidence. It is essential to avoid oversimplification by focusing on a single biomarker, as the interactions among multiple factors contribute to define the disease course and patient's outcome. Furthermore, implementing well-supported evidence in real-life settings can help advance prognostic biomarker research in melanoma.

Purpose: to report an uncommon presentation of Encorafenib-Binimetinib retinal side effects., Case Report: A 56-year-old Caucasian woman, naïve to previous chemotherapies, was started on Encorafenib/Binimetinib for metastatic melanoma. After seven hours from the first 45 mg Binimetinib dose, the patient developed blurry vision with coloured halos. The symptoms were transient and the following day a complete ophthalmological examination revealed the presence of subretinal fluid (SRF) at Optical coherence tomography (OCT). After one week, the patient remained asymptomatic, with no signs of SRF at the follow up reevaluation. However, six weeks later, the symptoms originally experienced with the first drug intake appeared again. This time fundus examination revealed an irregular macular region. At infrared OCT an almond shaped hyporeflective lesion, surrounded by hyperreflectivity, was demonstrated without signs of SRF. Encorafenib/Binimetinib was continued at the same dose and strict monitoring was scheduled, according to the European Medicine's Agency indication to withhold the drug only in presence of symptomatic retinal pigment epithelial detachment., Conclusion: Visual symptoms associated with SRF induced by Binimetinib have been described in the literature. In our case, visual symptoms were experienced by the patient at different times, both with and without evidence of SRF. This finding seems to suggest that while Binimetinib-induced SRF is an asymptomatic finding in most cases, with excellent outcome and rapid resolution, visual symptoms could be initially triggered by detectable SRF, yet persist without any further evidence of abnormal fluid accumulation and manifest intermittently., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Psoriasis is a chronic inflammatory skin disease whose molecular mechanisms and microenvironment are poorly understood. We performed gene expression analysis through the nCounter ® PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA) on 22 FFPE punch biopsies from 19 psoriasis-affected patients. A subset of five cases was analyzed before (T0) and after 6 months (T6) of treatment with dimethyl fumarate (DMF) to address immune microenvironment changes. Molecular comparisons according to biopsy site and age of onset showed a different distribution of innate immune cells (mast cells, macrophages, NK cells, and DC cells) and pathways (complement regulation and transporter functions). The analysis according to PASI (Psoriasis Area and Severity Index) led to non-significant results, suggesting no link between molecular expression profile and clinical amount of skin disease. In DMF-treated patients, we observed a strong immunomodulatory effect after treatment: A subversion of exhausted CD8 T cells, NK CD56dim cells, Tregs, neutrophils, CD45+ cells, T cells, B cells, and macrophages was reported between the two analyzed time-points, as well as the reduction in pro-inflammatory pathways and molecules, including cytotoxicity, pathogen defense, antigen processing, adhesion, cell cycle, chemokines, cytokines, and interleukins. The inflammatory psoriatic microenvironment can be modulated using DMF with encouraging results, achieving an immune-tolerant and non-inflammatory condition through the regulation of both innate and adaptive immunity.