Clinical utility of ingenol mebutate in the management of actinic keratosis. Perspectives from clinical practice

Actinic keratoses (AKs) are epidermal cutaneous neoplasia observed predominantly in middle-aged and older subjects with mainly photo type I and photo type II on sun-exposed surfaces as a result of DNA damage. AKs have historically been characterized as being "precancerous"; however, now it is considered by many authors a carcinoma in situ that can persist or progress to invasive squamous cell carcinoma (SCC) with metastatic potential. Despite the advances in the recognition of typical clinic, dermoscopic and histologic patterns, currently it is not yet possible to predict which AKs will progress to SCC. For this reason, early diagnosis and effective therapy are recommended based on cost/risk/benefit analysis. Current treatment consists of lesion-directed or field-directed therapies or a combination of both. Among the topical field therapies, ingenol mebutate stands out for its therapeutic efficacy, both as directed lesion therapy and as field directed therapy. The aim of this review is to demonstrate the utility of ingenol mebutate in the management of AK in daily clinical practice and to highlight data from real world in order to confirm evidence from pivotal studies. In order to explore clinical data from real world, PubMed searches were performed with the search terms "clinical data ingenol mebutate" and "real world ingenol mebutate". The hits were examined for relevant articles using defaults criteria. The timeframe for the sample search started from the first publication on this topic in 2008 up to now. A total of 23 articles were found using the keywords specified above. The overview points out a low number of real-life studies on the effectiveness and tolerability of this novel treatment due to short period of clinical experience for its recent approval. Further real-life studies are required in order to better identify the efficacy, safety and adherence of the drug on a larger population

Le Primavere Elleniche: una svolta nell'itinerario poetico di Giosue Carducci

La presente tesi di laurea si propone di studiare le Primavere Elleniche di Giosue Carducci,titolo con il quale si indicano tre odi composte nel biennio 1871-1872 e dedicate a Carolina Cristofori Piva, donna mantovana con la quale il poeta ebbe una relazione affettiva protrattasi dal 1872 al 1878. Dopo un'attenta analisi metrico-tematica dei testi e la ricognizione dei modelli letterari ai quali Carducci dovette in parte ispirarsi per la stesura di questi versi, sono fornite le chiavi interpretative con le quali le odi saranno esaminate nelle successive sezioni dell'elaborato. Nel secondo capitolo le Primavere Elleniche, lette in rapporto con l'epistolario carducciano e le poche missive che della Piva ci sono pervenute, sono presentate come componimenti direttamente ispirati da Lina, fautrice della metaforica rinascita del poeta in seguito agli avvenimenti luttuosi che segnarono la vita di quest'ultimo nel 1870 e, specie all'inizio della conoscenza tra i due, perfetto escamotage per intraprendere un nuovo discorso poetico di matrice neoclassica secondo la volontà espressa da Carducci di far ritorno all'arte pura, una poesia libera da ragioni extraletterarie. Tale decisione, argomento del terzo capitolo, deve essere interpretata come la necessità per il Vate di allontanarsi dalla produzione epodica e dalle questioni socio-politiche che vi erano connesse in seguito agli avvenimenti storici che interessarono la penisola italiana tra la fine degli anni Sessanta ed i primi Settanta, quando gli ideali repubblicani per i quali Carducci aveva da sempre combattutto si rivelarono vane speranze e la politica della Sinistra non riusciva in alcun modo a soddisfare un Enotrio Romano ormai disilluso. Le Primavere Elleniche in quest'ottica vogliono essere il critico controcanto alla poesia giambica ed uno stacco netto rispetto alla precedente produzione, il simbolo del ritorno all'arte pura e ad una poesia che, svincolatasi da ragioni contingenti, può davvero dirsi autonoma secondo quanto anticipato dal componimento Prologo e dall'ode Ad Alessandro D'Ancona. A questo punto dell'analisi emerge un concetto, quello di inizio della poetica neoclassica da un lato e di fine di quella epodica dall'altro, che mostra la strada da intraprendere per la terza ed ultima chiave interpretativa, oggetto del capitolo finale. Le Primavere Elleniche vengono quindi presentate come gli incunaboli delle future Odi Barbare (1877), con le quali numerose sono le affinità sia sul piano metrico che su quello tematico, passando prima attraverso la raccolta delle Nuove poesie (1873)

Gender matter in isotretinoin therapy for acne vulgaris? A retrospective study

Introduction: Gender differences have been recently highlighted for several aspects of acne vulgaris such as epidemiology, pathogenesis, clinical course, quality of life and treatment outcome. In particular a shorter but more severe clinical course has been reported in males than in females; nevertheless, usually men have their quality of life less affected. Aim: To determine if the response and the adverse events to 1 cycle of oral isotretinoin therapy can be influenced by gender. Methods: A retrospective study was conducted on consecutive patients affected by acne vulgaris and treated with oral isotretinoin. Global acne grading system (GAGS), acne-related quality of life (AQoL) and isotretinoin-related adverse events were considered as outcome measures and were evaluated before (T0), every month during administration and 4 weeks after the withdrawal (T1) of oral isotretinoin therapy. Mann-Whitney U test and Wilcoxon signed-rank test were used for quantitative parameters and Fisher exact test for qualitative ones. Results: Forty-nine acneic patients were retrospectively selected (33 males 67.3% and 16 females -32.7%; median age: 19 years). Patients had received a median dosage of isotretinoin of 0.4 mg/kg/die for a median period of 5 months; no differences in outcome measures among genders were reported. Limitations: The study is retrospective and the sample is small and not homogenously distributed among genders, as males are double in number than females. Conclusions: In our study population gender didn't influence neither the clinical and the quality of life outcome measures nor the occurrence of adverse events to oral isotretinoin therapy for acne

First data on plastic ingestion by blue sharks (Prionace glauca) from the Ligurian Sea (North-Western Mediterranean Sea)

Few studies have focused so far on plastic ingestion by sharks in the Mediterranean Sea. The aim of this paper was to determine, for the first time, the plastic litter ingested by blue sharks (Prionace glauca), categorized as \u201cCritically Endangered\u201d in the Mediterranean Sea by IUCN, caught in the Pelagos Sanctuary SPAMI (North-Western Mediterranean Sea). The analysis of the stomach contents was performed following the MSFD Descriptor 10 standard protocol implemented with FT-IR spectroscopy technique. The results showed that 25.26% of sharks ingested plastic debris of wide scale of sizes from microplastics (<5 mm) to macroplastics (>25 mm). The polyethylene sheetlike user plastics, widely used as packaging material, are the most ingested debris. This research raises a warning alarm on the impact of plastic debris on a threatened species, with a key role in the food web, and adds important information for futures mitigation actions

iga anticardiolipin in patients with gastroenteric tumor

Recently the presence of antiphospholipid antibodies in patients with cancer has been demonstrated, suggesting an involvement of autoimmune response in neoplastic conditions. The presence of antiphospholipid antibodies in tumor disease is highly correlated with the risk of developing thrombotic complications, which represents a significant cause of morbidity and mortality in cancer patients. Interestingly, it has been highlighted that high levels of IgM and IgG anticardiolipin antibodies are more often produced in patients with gastroenteric tumor than in patients with either ovarian or breast tumor. Thus far, there are no data looking into the role or measurements of IgA in patients with solid cancer. Our preliminary results, in this study, demonstrate that testing only for IgG and IgM anticardiolipin antibodies may increase the incidence of false positive because 44% who were IgA positive and IgG and IgM negative had high titres of CA19.9 and CEA. We suggest that taking into account the role of IgA could substantially improve the detection of antiphospholipids antibodies in subjects with solid cancer, and this detection may allow us for better prevention and management of thrombotic complications in these patients

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score

A New Approach to Land-Use Structure. Patch Perimeter Metrics as a Spatial Analysis Tool

This work introduces a new class of landscape metrics characterizing basic features of patch perimeters. Specific computation on patch perimeters was carried out on fine-grained land-use maps with the aim to characterize spatial patterns of neighbor patches, evidencing contact points and perimeter length between two (or more) land-use types. A detailed set of class and landscape metrics were derived from such analysis. This approach is complementary to classical landscape metrics and proved to be particularly useful to characterize complex, fragmented landscapes profiling metropolitan regions based on integrated evaluations of their structural (landscape) and functional (land-use) organization. A multivariate analysis was run to characterize distinctive spatial patterns of the selected metrics in four metropolitan regions of southern Europe reflecting different morphological configurations (Barcelona: compact, polycentric; Lisbon: dispersed, mono-centric; Rome: dispersed, polycentric; and Athens: compact, mono-centric). Perimeter metrics assumed different values for each investigated land-use type, with peculiar characteristics associated to each city. Land-use types assessing residential, discontinuous urban patches were associated to particularly high values of perimeter metrics, possibly indicating patch fragmentation, spatially-associated distribution of land-use types and landscape complexity. Multivariate analysis indicates substantial differences among cities, reflecting the range of morphological configurations described above (from compact mono-centric to dispersed polycentric) and suggesting that urban expansion is accompanied with multiple modifications in the use of the surrounding non-urban land. The computational approach proposed in this study and based on spatially-explicit metrics of landscape configuration and proximity may reflect latent changes in local socio-spatial structures. Our results demonstrate that scattered urban expansion determines a polarization in suburban areas with highly fragmented and more homogeneous landscapes, respectively, associated with mixed cropland and forest systems

Energy Transfer from Magnetic Iron Oxide Nanoparticles: Implications for Magnetic Hyperthermia

Magnetic iron oxide nanoparticles (IONPs) have gained momentum in the field of biomedical applications. They can be remotely heated via alternating magnetic fields, and such heat can be transferred from the IONPs to the local environment. However, the microscopic mechanism of heat transfer is still debated. By X-ray total scattering experiments and first-principles simulations, we show how such heat transfer can occur. After establishing structural and microstructural properties of the maghemite phase of the IONPs, we built a maghemite model functionalized with aminoalkoxysilane, a molecule used to anchor (bio)molecules to oxide surfaces. By a linear response theory approach, we reveal that a resonance mechanism is responsible for the heat transfer from the IONPs to the surroundings. Heat transfer occurs not only via covalent linkages with the IONP but also through the solvent hydrogen-bond network. This result may pave the way to exploit the directional control of the heat flow from the IONPs to the anchored molecules─i.e., antibiotics, therapeutics, and enzymes─for their activation or release in a broader range of medical and industrial applications

Efficacy of Cemiplimab in a patient affected by Cutaneous Squamous Cell Carcinoma and Myelodysplastic Syndrome

Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin malignancy, often managed through surgical intervention. However, in certain cases, especially when complicated by concurrent hematologic disorders such as myelodysplastic syndrome (MDS), treatment options become more challenging. This abstract highlights a case study examining the efficacy of cemiplimab, a monoclonal antibody targeting programmed cell death protein 1 (PD-1), in a patient diagnosed with both cSCC and MDS. The patient, initially presenting with an advanced cSCC lesion and underlying MDS, underwent treatment with cemiplimab as a therapeutic approach. Monitoring of the patient's response included clinical evaluation, radiological assessments, and laboratory analyses. Results demonstrated a notable reduction in the size of the cSCC lesion and stabilization of hematologic parameters, suggesting a positive therapeutic effect of cemiplimab in this complex clinical scenario. This case underscores the potential utility of immunotherapeutic agents, specifically PD-1 inhibitors like cemiplimab, in the management of cutaneous malignancies coexisting with hematologic disorders. Further investigations and larger-scale studies are warranted to validate these findings and establish cemiplimab's role as a viable treatment option in similar clinical contexts