The Diagnosis and Management of Cutaneous Metastases from Melanoma

Melanoma is one of the deadliest skin tumors, accounting for almost 90% of skin cancer mortality. Although immune therapy and targeted therapy have dramatically changed the prognosis of metastatic melanoma, many patients experience disease progression despite the currently available new treatments. Skin metastases from melanoma represent a relatively common event as first sign of advanced disease or a sign of recurrence. Skin metastases are usually asymptomatic, although in advanced stages, they can present with ulceration, bleeding, and superinfection; furthermore, they can cause symptoms related to compression on nearby tissues. Treatments vary from simple surgery resections to topical or intralesional local injections, or a combination of these techniques with the most recent systemic immune or target therapies. New research and studies should focus on the pathogenesis and molecular mechanisms of the cutaneous metastases of melanoma in order to shed light on the mechanisms underlying the different behavior and prognoses of different patients

Dupilumab for Treatment of Prurigo Nodularis: Real-Life Effectiveness for up to 84 Weeks

: (1) background: prurigo nodularis (PN) is a persistent and inflammatory dermatological condition characterized by chronic itching and the formation of hardened nodules, significantly impacting the affected individuals' quality of life and psychological well-being. the management of PN poses challenges due to the limited efficacy and undesirable side effects associated with current interventions. (2) methods: this article examines sixteen patients affected by PN treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. this involves a retrospective descriptive statistical analysis. (3) results and (4) conclusions: In all patients, dupilumab proves to be an effective drug in achieving disease clearance, as indicated by all the parameters considered as assessed by both physicians and patients at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, and Week 84), in comparison to the initial baseline

Efficacy and Safety of Dupilumab in the Treatment of Hand Eczema: A Retrospective Study

Background: Hand eczema (HE) is a prevalent chronic condition that exerts a substantial and enduring adverse effect on quality of life (QoL) and imposes an economic burden on society. Managing HE poses challenges due to the limited effectiveness and potential adverse effects associated with many currently available topical and systemic treatments. Methods: This article examines twenty-one patients affected by HE treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. Results: At week 6, HECSI-75 was achieved by 12 patients (57.9%). The proportion of patients meeting the HECSI-75 criteria steadily increased over the observation weeks, reaching 90% at week 16 and 100% at week 104. Furthermore, HECSI-90 and HECSI-100 were achieved by 75% and 60% of patients at week 16 and by 100% and 85% of patients at week 68, respectively. All patients who reached week 104 maintained complete disease remission according to HECSI 100. Conclusions: In all patients, dupilumab was shown to be an effective drug in achieving disease clearance, as indicated by all the parameters considered at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, Week 84, and Week 104), in comparison to the initial baseline

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Rosacea-like eruptions associated with upadacitinib in atopic dermatitis: two case reports and management strategies

Atopic dermatitis (AD) is a chronic inflammatory skin disease often requiring systemic therapies for moderate-to-severe cases. Janus kinase (JAK) inhibitors, including upadacitinib, have emerged as effective options, targeting pro-inflammatory cytokines involved in AD pathogenesis. However, adverse dermatologic reactions, such as rosacea-like eruptions, have been observed, potentially linked to immune pathway modulation. This report describes two patients with severe AD who achieved complete disease clearance with upadacitinib but developed rosacea-like eruptions. Both cases required discontinuation of the drug and treatment with antibiotics, which resolved the symptoms. However, withdrawal led to AD flares in one patient, necessitating the reintroduction of upadacitinib at a reduced dose combined with prophylactic antibiotics. These cases underscore the efficacy of JAK inhibitors while highlighting the challenge of managing adverse effects. Individualized treatment approaches, including dose adjustments and adjunctive therapies, are essential for balancing AD control with tolerability. Further research is needed to optimize the management of these reactions

Severe paradoxical generalized pustular psoriasis induced by adalimumab biosimilar successfully treated with brodalumab

Paradoxical psoriasis is a rare but increasingly recognized adverse effect of anti-TNF-α therapy, characterized by the onset or exacerbation of psoriatic lesions in patients treated for other immune-mediated conditions. We report the case of a 47-year-old woman with chronic plaque psoriasis who developed severe generalized pustular psoriasis (GPP) after six months of treatment with an adalimumab biosimilar. Given the extent and severity of the eruption and following inadequate response to previous conventional therapies, the patient was treated with brodalumab, an IL-17RA inhibitor. Rapid and complete remission of both pustular and plaque psoriasis was achieved and maintained for over 60 weeks. This case supports the efficacy of IL-17 pathway blockade in managing paradoxical GPP and highlights the importance of prompt recognition and appropriate therapeutic switching in severe biologic-induced psoriasis

Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides

background: the neutrophil/lymphocyte ratio (NLR) at baseline has been demonstrated to correlate with higher stages of disease and to be a prognostic factor in numerous cancers. however, its function as a prognostic factor for mycosis fungoides (MF) has not been yet clarified. objective: our work aimed to assess the association of the NLR with different stages of MF and to outline whether higher values of this marker are related to a more aggressive MF.methods: we retrospectively calculated the NLRs in 302 MF patients at the moment of diagnosis. the NLR was obtained using the complete blood count values.results: the median NLR among patients with early stage disease (low-grade IA-IB-IIA) was 1.88, while the median NLR for patients with high-grade MF (IIB-IIIA-IIIB) was 2.64. statistical analysis showed positive associations of advanced MF stages with NLRs higher than 2.3. conclusions: our analysis demonstrates that the NLR represents a cheap and easily available parameter functioning as a marker for advanced MF. this might guide physicians in recognizing patients with advanced stages of disease requiring a strict follow-up or an early treatment

Circulating Tumor Cells: Origin, Role, Current Applications, and Future Perspectives for Personalized Medicine

Circulating tumor cells (CTCs) currently represent a revolutionary tool offering unique insights for the evaluation of cancer progression, metastasis, and response to therapies. Indeed, CTCs, upon detachment from primary tumors, enter the bloodstream and acquire a great potential for their use for personalized cancer management. In this review, we describe the current understanding of and advances in the clinical employment of CTCs. Although considered rare and fleeting, CTCs are now recognized as key players favoring the development of cancer metastasis and disease recurrence, particularly in malignant melanoma, lung, breast, and colorectal cancer patients. To date, the advancements in technology and the development of several successful approaches, also including immunomagnetic enrichment allow for a reliable and reproducible detection and characterization of CTCs. Those innovative methodologies improved the isolation, quantification, and characterization of CTCs from the blood of cancer patients, providing extremely useful evidence and new insights into the nature of the tumor, its epithelial/mesenchymal profile, and its potential resistance to therapy. In fact, in addition to their prognostic and predictive value, CTCs could serve as a valuable instrument for real-time monitoring of treatment response and disease recurrence, facilitating timely interventions and thus improving patient outcomes. However, despite their potential, several challenges hinder the widespread clinical utility of CTCs: (i) CTCs&rsquo; rarity and heterogeneity pose technical limitations in isolation and characterization, as well as significant hurdles in their clinical implementation; (ii) it is mandatory to standardize CTC detection methods, optimize the sample processing techniques, and integrate them with existing diagnostic modalities; and (iii) the need for the development of new techniques, such as single-cell analysis platforms, to enhance the sensitivity and specificity of CTC detection, thereby facilitating their integration into routine clinical practice. In conclusion, CTCs represent a potential extraordinary tool in cancer diagnostics and therapeutics, offering unprecedented opportunities for personalized medicine and precision oncology. Moreover, their ability to provide real-time insights into tumor biology, treatment response, and disease progression underlines a great potential for their clinical application to improve patients&rsquo; outcomes and advance our understanding of cancer biology

Epithelial-to-Mesenchymal Transition Gene Signature in Circulating Melanoma Cells: Biological and Clinical Relevance

The most promising method for monitoring patients with minimal morbidity is the detection of circulating melanoma cells (CMCs). We have shown that CD45&minus;CD146+ABCB5+ CMCs identify a rare primitive stem/mesenchymal CMCs population associated with disease progression. The epithelial-to-mesenchymal transition (EMT) confers cancer cells a hybrid epithelial/mesenchymal phenotype promoting metastatization. Thus, we investigated the potential clinical value of the EMT gene signature of these primitive CMCs. A reliable quantitative real-time polymerase chain reaction (qRT-PCR) protocol was settled up using tumor cell lines RNA dilutions. Afterwards, immune-magnetically isolated CMCs from advanced melanoma patients, at onset and at the first checkpoint (following immune or targeted therapy), were tested for the level of EMT hallmarks and EMT transcription factor genes. Despite the small cohort of patients, we obtained promising results. Indeed, we observed a deep gene rewiring of the EMT investigated genes: in particular we found that the EMT gene signature of isolated CMCs correlated with patients&rsquo; clinical outcomes. In conclusion, We established a reliable qRT-PCR protocol with high sensitivity and specificity to characterize the gene expression of isolated CMCs. To our knowledge, this is the first evidence demonstrating the impact of immune or targeted therapies on EMT hallmark gene expressions in CMCs from advanced melanoma patients

PIANO DI GESTIONE DEL SITO UNESCO VILLA ROMANA DEL CASALE

An effective asset management system must consider three essential elements, namely a reference legal framework that defines the reasons for its very existence, an institution that shapes organizational and decision-making needs and resources, human, financial and intellectual, used to make it operational. Having clarified the areas and the meaning of these three decisive elements, it becomes easier to plan, implement and monitor the actions identified to ensure the conservation and management of the assets and values associated with them in a sustainable way. The management systems are aimed at achieving results that benefit the site and its stakeholders and include planning, implementation and monitoring cycles, aimed at carrying out activities aimed at conservation, interpretation and access to the site, also taking care of the sustainable use and sharing of benefits. Obviously each management system must be regularly reviewed and updated in order to respond to changes in the site and in the context, making the necessary adjustments. With the powerful work undertaken by Civita to update the three Management Plans of the UNESCO sites of "val di Noto", "Siracusa and the Necropolis of Pantalica" and "villa romana del Casale" of Piazza Armerina, the goal was to develop an integrated system of the three different floors, related to three different contiguous sites, which has no precedent. From this unprecedented and extraordinary coordination it will be possible to reap mutual benefits, economies of scale and common strategies, for example, linked to the unpredictability of the risk of natural disasters or fluctuations in financial resources. Particular emphasis must be given to the participatory approach used in the drafting of the three Management Plans, through the shared understanding of the site, and its identity, by all interested parties with their involvement in the construction of technical contributions that is premised on involvement in management processes and also foundations- efficiency in terms of reactivity that only the continuous exchange of results and outputs can ensure, feeding the monitoring and reprogramming phases