Centro Studi GISED

Eggplant (Solanum melongena L.) is a major Solanaceous crop of Asian origin, but genomic resources remain limited compared to related species. Here, a core collection of 368 accessions spanning global diversity of S. melongena and wild relatives is phenotyped for agronomic, disease resistance and fruit metabolomic traits and resequenced. Additionally, 40 chromosome-level assemblies of S. melongena, its progenitor S. insanum and the allied species S. incanum enable the construction of two graph-based pangenomes, capturing broad genetic variation. We demonstrate the power of these datasets by identifying major loci controlling prickliness and resistance to Fusarium oxysporum f. sp. melongenae, driven by SVs affecting the LONELY GUY 3 gene and a resistance gene cluster, respectively, as well as a mutation in a GDSL-like esterase/lipase gene altering the levels of dicaffeoyl-quinic acids. These findings provide a cornerstone for pangenome-assisted breeding, enabling detailed analyses of genetic diversity, domestication history, and trait evolution in eggplant.

Introduction The Psoriasis Longitudinal Assessment and Registry (PSOLAR; NCT00508547) is a large, international, prospective, longitudinal, disease-based registry that enrolled patients with psoriasis (PsO) who were receiving, or were candidates for, systemic therapy. The aims of the Registry are to assess the long-term safety and improve understanding of real-world biologic use in patients with PsO. Objective The objective of this analysis is to describe real-world effectiveness of guselkumab in patients with psoriasis. Methods Disease characteristics, absolute Psoriasis Area and Severity Index (PASI) score, percentage of body surface area (BSA) involvement, and change from baseline in PASI score and BSA through two years are reported for patients with PsO treated with guselkumab (GUS). Some patients initiated GUS ahead of enrolment in the registry. Results As of 12 July 2024, 2198 patients who initiated GUS prior to, or at, enrolment were included with a mean (standard deviation [SD]) duration of follow-up of 3.02 (1.08) years. Of these, 1184 (53.9%) were from North America, 672 (30.6%) were from Europe and 342 (15.6%) were from the Asia-Pacific region. Through 2 years of treatment, 244 (11.1%) patients withdrew from the registry, with the most common reason for withdrawal being patient choice (n=96, 39.3%) and 48 (19.7%) patients being lost to follow-up. Most patients had plaque PsO (2140, 97.4%) with a mean (SD) baseline PASI score of 6.0 (7.02) and a mean (SD) BSA involvement of 8.9% (12.72%). At baseline, 427 (21.1%) patients had a PASI score of 0, 188 (9.3%) had PASI >0–<1, 199 (9.8%) had PASI ≥1–<2, 160 (7.9%) had PASI ≥2–<3, 231 (11.4%) had PASI ≥3–<5 and 816 (40.4%) had PASI ≥5. Approximately 1 in 4 GUS patients had a PASI score of >10 (n=496; 24.5%). At Month 6, the mean (SD) change from baseline in PASI score was −4.5 (7.06) and the mean (SD) change from baseline in %BSA was −6.6 (12.41), corresponding to a mean (SD) absolute PASI score of 1.6 (3.10) and a mean (SD) BSA of 2.3% (5.81%), respectively. Improvements were maintained through 1 year of therapy; at Month 12, the mean (SD) change from baseline in PASI score was −4.4 (6.96) and in %BSA was −6.8 (12.26), corresponding to mean (SD) absolute PASI score of 1.5 (2.74) and a mean (SD) BSA of 1.9% (4.79%). Improvements were maintained through 2 years of treatment, with a mean (SD) absolute PASI score of 1.5 (3.13) and a mean (SD) BSA of 2.1% (6.08%), respectively. Conclusion: Patients in this large real-world registry experienced improvements in PsO severity while receiving treatment with GUS. Improvements were maintained through 2 years of treatment, supporting the use of GUS as a highly effective long-term option for patients with PsO.

Acne and acne sequelae can have an important impact on patients' quality of life, affecting interpersonal relationships and social functioning. Acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH), in particular, are a major concern for patients with acne, as their management is challenging and often unsatisfactory. Retinoids are considered the mainstay of acne treatment because of their action on multiple pathogenetic factors, and there is increasing evidence that they can also improve AIS and AIH. Trifarotene, a topical retinoid with selectivity for retinoic acid receptor (RAR)-γ, has undergone an extensive clinical development programme, demonstrating its efficacy in treating facial and truncal acne and improving acne sequelae. In this article, we review the main evidence supporting the use of trifarotene in patients with acne and acne sequelae and provide place-in-therapy suggestions based on the experience of the Italian Acne Board with this drug in real-life practice. Trifarotene can be used successfully, as monotherapy or in association with other treatments, in most clinical settings of acne, but it plays an essential role in patients with existing AIS and AIH, those with a clinical or personal history of scarring and those who are predisposed to AIH. Owing to its long-term efficacy and tolerability, trifarotene is also a good option as a maintenance treatment. As with other topical retinoids, patients undergoing trifarotene therapy should be given advice on how to minimise local irritation when starting treatment.

Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2). To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo. OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator's Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods. Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks. The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16. Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity. In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN. ClinicalTrials.gov Identifier: NCT04501666.

Background: Chronic leg ulcers present a global challenge in healthcare, necessitating precise wound measurement for effective treatment evaluation. This study is the first to validate the "split-wound design" approach for wound studies using objective measures. We further improved this relatively new approach and combined it with a semi-automated wound measurement algorithm. Method: The algorithm is capable of plotting an objective halving line that is calculated by splitting the bounding box of the wound surface along the longest side. To evaluate this algorithm, we compared the accuracy of the subjective wound halving of manual operators of different backgrounds with the algorithm-generated halving line and the ground truth, in two separate rounds. Results: The median absolute deviation (MAD) from the ground truth of the manual wound halving was 2% and 3% in the first and second round, respectively. On the other hand, the algorithm-generated halving line showed a significantly lower deviation from the ground truth (MAD = 0.3%, p < 0.001). Conclusions: The data suggest that this wound-halving algorithm is suitable and reliable for conducting wound studies. This innovative combination of a semi-automated algorithm paired with a unique study design offers several advantages, including reduced patient recruitment needs, accelerated study planning, and cost savings, thereby expediting evidence generation in the field of wound care. Our findings highlight a promising path forward for improving wound research and clinical practice.

Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.SIGNIFICANCEThis study examines the question as to whether the perception of skin dryness and sensitivity differs between patients with psoriasis and controls. In this population-based survey (cross-sectional study) of 11,283 participants, subjects with psoriasis reported a higher prevalence of dry (71.1%) and sensitive (49.4%) skin than those without psoriasis (51.6% and 38.5%, respectively). However, no significant differences in patch-test results were observed between the 2 groups. Finally, the study found that people with psoriasis perceived their skin as drier and more sensitive than controls, regardless of psoriasis severity, highlighting the importance of addressing subjective perceptions in treatment strategies.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

ABSTRACT Introduction Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD. Similar results were reported in a phase 3 trial in adolescents (aged ≥12 years). Areas covered We review the role of IL-13 in AD and discuss the value of tralokinumab for treating moderate-to-severe AD, comparing efficacy and safety results derived from clinical trials and real-life data. Expert opinion The role of IL-13 in AD supports a targeted therapeutic approach. Tralokinumab has proven efficacious and well-tolerated in a large proportion of patients confirming its value for treating moderate-to-severe AD from age 12 years onwards; it quickly improves itching and can maintain a high-level of response over time; it can be administered with flexible dosing schedules. Future studies will further clarify the role of IL-13 pathway and which patients would be best suited to tralokinumab, shifting AD treatment into an era of precision medicine.

Journal Article Accepted manuscript Decoding Atopic Dermatitis: Unveiling Phenotypes Through Data-Driven Methods Get access Simone Cazzaniga, Simone Cazzaniga Department of Dermatology, Inselspital University Hospital of Bern, Bern, SwitzerlandCentro Studi GISED, Bergamo, Italy Correspondence: Simone Cazzaniga, Email:simone.cazzaniga@gised.it https://orcid.org/0000-0001-8161-6138 Search for other works by this author on: Oxford Academic Google Scholar Dagmar Simon Dagmar Simon Department of Dermatology, Inselspital University Hospital of Bern, Bern, Switzerland https://orcid.org/0000-0001-8965-9407 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad453, https://doi.org/10.1093/bjd/ljad453 Published: 17 November 2023 Article history Editorial decision: 10 November 2023 Received: 10 November 2023 Accepted: 16 November 2023 Published: 17 November 2023