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(1) Background: The purpose of this study is to compare the rate of COVID-19 vaccination among psoriasis patients internationally and to correlate it with their treatment regimens. (2) Methods: We conducted a cross-sectional study from January 2021 to October 2022 among adults in the United States (US), Chile, China, Switzerland, and Singapore using the Global Healthcare Study on Psoriasis survey. (3) Results: A total of 310 psoriasis patients in the US (98), Chile (32), China (80), Switzerland (39), and Singapore (61) were surveyed. Of these, 248 patients (80.0%) were vaccinated at least once for COVID-19 (Chile: 100%, Singapore: 100%, US: 93.9%, Switzerland: 69.2%, China: 45.0%). Compared with other countries, patients in China were 89% less likely to report at least one COVID-19 vaccination (1 − 0.11 = 0.89; OR 0.11; 95% CI: 0.03–0.48), and patients in Switzerland were 80% less likely (1 − 0.20 = 0.80; OR 0.20; 95% CI: 0.05–0.79). Compared with patients on biologics, patients on topicals were 10.9 (95% CI: 2.1–56.6) times more likely to report at least one COVID-19 vaccination, and patients on oral systemics were 7.2 times more likely (95% CI: 1.6–31.6). (4) Conclusions: Country of residence and treatment regimen are associated with different COVID-19 vaccination rates in psoriasis patients. [ABSTRACT FROM AUTHOR]

Vaccine hesitancy has been a contentious issue even before the pandemic. The COVID-19 crisis has further amplified vaccine hesitancy, with worries about adverse effects, cultural and religious beliefs, and misinformation on social media. In dermatology, patients with pre-existing skin conditions may have specific concerns about the impact of the vaccine on their skin health. Factors such as cutaneous reactions, potential flares of underlying conditions, and fears of psoriasis worsening post-vaccination contribute to vaccine hesitancy. Healthcare professionals, including dermatologists, play a crucial role in addressing vaccine hesitancy by providing accurate information, addressing concerns, and understanding the psychological impact on patients. The concept of vaccine fatigue is also explored, noting the challenges in sustaining vaccine acceptance over time, especially with regards to booster vaccinations. Overcoming vaccine hesitancy requires trust-building, effective communication strategies, and collaboration between healthcare workers and non-healthcare individuals to combat misinformation. By recognizing and addressing psychological factors, dermatologists can increase vaccine acceptance and improve public health efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we thoroughly explore the clinical and biological features of immunotherapy-induced vitiligo-like depigmentation (VLD) in patients with stage III-IV melanoma receiving immunotherapy. Key findings include a distinct immune signature with an upregulation of ITGA in the VLD group, an upregulation of EDAR and downregulation of LAG3 in VLD-responders group, a longer time to VLD onset in patients pre-treated with targeted therapy, the distribution of VLD lesions primarily in sun-exposed areas as opposed to mechanically stressed areas in non-immunotherapy-related vitiligo, the predominance of a symmetrical, small-freckle lesional pattern and a prolonged progression-free survival (PFS) and overall survival (OS) in VLD patients without LDH elevation as opposed to those with LDH elevation. Vitiligo-like depigmentation (VLD) is an immune-related adverse event (irAE) of checkpoint-inhibitor (CPI) treatment, which has previously been associated with a favourable outcome. The aim of this study was to explore clinical, biological and prognostic features of melanoma patients with VLD under CPI-treatment and to explore whether they exhibit a characteristic immune response profile in peripheral blood. Melanoma patients developing VLD under CPI were included in a prospective observational single-center cohort study. We collected and analysed clinical parameters, photographs and serum from 28 VLD patients. They received pembrolizumab (36%), nivolumab (11%), ipilimumab/nivolumab (32%) or clinical trial medications (21%). We performed a high-throughput proteomics assay (Olink), in which we identified a distinct proteomic signature in VLD patients in comparison to non-VLD CPI patients. Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller "freckle-like" macules and a preferential distribution in UV-exposed areas. Patients with previous targeted therapy showed a significantly longer time lapse between CPI initiation and VLD onset compared to non-pre-treated patients (12.5 vs. 6.25 months). Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3. ITGA11 was elevated in the VLD-group when compared to non-VLD-CPI-treated melanoma patients. Our findings demonstrate that on a proteomic level, VLD is characterized by a distinct immune signature when compared to CPI-treated patients without VLD and that therapy responsiveness is reflected by a characteristic immune profile. The pathomechanisms underlying these findings and how they could relate to the antitumoral response in melanoma remain to be elucidated. [ABSTRACT FROM AUTHOR]

Simple Summary: Early detection and resection of cutaneous melanoma are crucial for a good prognosis. However, visual distinction of early melanomas from benign nevi remains challenging. New artificial intelligence-based approaches for risk stratification of pigmented skin lesions provide screening methods for laypersons with increasing use of smartphone applications (apps). Our study aims to prospectively investigate the diagnostic accuracy of a CE-certified smartphone app, SkinVision®, in melanoma recognition. Based on classification into three different risk scores, the app provides a recommendation to consult a dermatologist. In addition, both patients' and dermatologists' perspectives towards AI-based mobile health apps were evaluated. We observed that the app classified a significantly higher number of lesions as high-risk than dermatologists, which would have led to a clinically harmful number of unnecessary excisions. The diagnostic performance of the app in dichotomous classification of 1204 pigmented skin lesions (risk classification for nevus vs. melanoma) remained below advertised rates with low sensitivity (41.3–83.3%) and specificity (60.0–82.9%). The confidence in the app was low among both patients and dermatologists, and no patient favored an assessment by the app alone. Although smartphone apps are a potential medium for increasing awareness of melanoma screening in the lay population, they should be evaluated for certification with prospective real-world evidence. The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 CE-certified smartphone app in melanoma risk stratification and its patient and dermatologist satisfaction. Pigmented skin lesions ≥ 3 mm and any suspicious smaller lesions were assessed by the smartphone app SkinVision® (SkinVision® B.V., Amsterdam, the Netherlands, App-Version 6.8.1), 2D FotoFinder ATBM® master (FotoFinder ATBM® Systems GmbH, Bad Birnbach, Germany, Version 3.3.1.0), 3D Vectra® WB360 (Canfield Scientific, Parsippany, NJ, USA, Version 4.7.1) total body photography (TBP) devices, and dermatologists. The high-risk score of the smartphone app was compared with the two gold standards: histological diagnosis, or if not available, the combination of dermatologists', 2D and 3D risk assessments. A total of 1204 lesions among 114 patients (mean age 59 years; 51% females (55 patients at high-risk for developing a melanoma, 59 melanoma patients)) were included. The smartphone app's sensitivity, specificity, and area under the receiver operating characteristics (AUROC) varied between 41.3–83.3%, 60.0–82.9%, and 0.62–0.72% according to two study-defined reference standards. Additionally, all patients and dermatologists completed a newly created questionnaire for preference and trust of screening type. The smartphone app was rated as trustworthy by 36% (20/55) of patients at high-risk for melanoma, 49% (29/59) of melanoma patients, and 8.8% (10/114) of dermatologists. Most of the patients rated the 2D TBP imaging (93% (51/55) resp. 88% (52/59)) and the 3D TBP imaging (91% (50/55) resp. 90% (53/59)) as trustworthy. A skin cancer screening by combination of dermatologist and smartphone app was favored by only 1.8% (1/55) resp. 3.4% (2/59) of the patients; no patient preferred an assessment by a smartphone app alone. The diagnostic accuracy in clinical practice was not as reliable as previously advertised and the satisfaction with smartphone apps for melanoma risk stratification was scarce. MHealth apps might be a potential medium to increase awareness for melanoma screening in the lay population, but healthcare professionals and users should be alerted to the potential harm of over-detection and poor performance. In conclusion, we suggest further robust evidence-based evaluation before including market-approved apps in self-examination for public health benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Concerns about potential diagnostic delays due to pandemic-related disruptions were expressed early during the COVID-19 outbreak. In the present study, we investigated the impact of the Swiss COVID-19 lockdown between March and June 2020 on newly diagnosed melanomas. Our main findings include a short-term rise in melanoma diagnoses after the major lift of social lockdown restrictions. Further, the analyzed prognostic factor for melanomas, the Breslow thickness, was greater in elderly female patients during the lockdown compared to the pre- and post-lockdown period. In addition, proportionally more stage IV melanomas were diagnosed during the lockdown period. Our study highlights the need for an adjusted management of cancer patients in future pandemic management strategies. At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis. In this retrospective, exploratory cohort study, 1240 patients with a new diagnosis of melanoma were analyzed at five tertiary care hospitals in German-speaking Switzerland over a period of two years and three months. We compared the pre-lockdown (01/FEB/19–15/MAR/20, n = 655) with the lockdown (16/MAR/20–22/JUN/20, n = 148) and post-lockdown period (23/JUN/20–30/APR/21, n = 437) by evaluating patients' demographics and prognostic features using Breslow thickness, ulceration, subtype, and stages. We observed a short-term, two-week rise in melanoma diagnoses after the major lift of social lockdown restrictions. The difference of mean Breslow thicknesses was significantly greater in older females during the lockdown compared to the pre-lockdown (1.9 ± 1.3 mm, p = 0.03) and post-lockdown period (1.9 ± 1.3 mm, p = 0.048). Thickness increase was driven by nodular melanomas (2.9 ± 1.3 mm, p = 0.0021; resp. 2.6 ± 1.3 mm, p = 0.008). A proportional rise of advanced melanomas was observed during lockdown (p = 0.047). The findings provide clinically relevant insights into lockdown-related gender- and age-dependent effects on melanoma diagnosis. Our data highlight a stable course in new melanomas with a lower-than-expected increase in the post-lockdown period. The lockdown period led to a greater thickness in elderly women driven by nodular melanomas and a proportional shift towards stage IV melanoma. We intend to raise awareness for individual cancer care in future pandemic management strategies. [ABSTRACT FROM AUTHOR]

Apremilast (Otezla®) is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet's disease. While PDE4 inhibition overall is mechanistically understood, the effect of apremilast on the innate immune response, particularly inflammasome activation, remains unknown. Here, we assessed the effect of apremilast in a psoriasis mouse model and primary human cells. Psoriatic lesion development in vivo was studied in K5.Stat3C transgenic mice treated with apremilast for 2 weeks, resulting in a moderate (2 mg/kg/day) to significant (6 mg/kg/day) resolution of inflamed plaques after 2-week treatment. Concomitantly, epidermal thickness dramatically decreased, the cutaneous immune cell infiltrate was reduced, and proinflammatory cytokines were significantly downregulated. Additionally, apremilast significantly inhibited lipopolysaccharide- or anti-CD3-induced expression of proinflammatory cytokines in peripheral mononuclear cells (PBMCs). Notably, inflammasome activation and secretion of IL-1β were not inhibited by apremilast in PBMCs and in human primary keratinocytes. Collectively, apremilast effectively alleviated the psoriatic phenotype of K5.Stat3 transgenic mice, further substantiating PDE4 inhibitor-efficiency in targeting key clinical, histopathological and inflammatory features of psoriasis. Despite lacking direct effect on inflammasome activation, reduced priming of inflammasome components upon apremilast treatment reflected the indirect benefit of PDE4 inhibition in reducing inflammation. [ABSTRACT FROM AUTHOR]

Lung nodules are frequent findings in chest computed tomography (CT) in patients with metastatic melanoma. In this study, we assessed the frequency and compared morphologic differences of metastases and benign nodules. We retrospectively evaluated 85 patients with melanoma (AJCC stage III or IV). Inclusion criteria were ≤20 lung nodules and follow-up using CT ≥183 days after baseline. Lung nodules were evaluated for size and morphology. Nodules with significant growth, nodule regression in line with RECIST assessment or histologic confirmation were judged to be metastases. A total of 438 lung nodules were evaluated, of which 68% were metastases. At least one metastasis was found in 78% of patients. A 10 mm diameter cut-off (used for RECIST) showed a specificity of 95% and a sensitivity of 20% for diagnosing metastases. Central location (n = 122) was more common in metastatic nodules (p = 0.009). Subsolid morphology (n = 53) was more frequent (p < 0.001), and calcifications (n = 13) were solely found in non-metastatic lung nodules (p < 0.001). Our data show that lung nodules are prevalent in about two-thirds of melanoma patients (AJCC stage III/IV) and the majority are metastases. Even though we found a few morphologic indicators for metastatic or non-metastatic lung nodules, morphology has limited value to predict the presence of lung metastases. [ABSTRACT FROM AUTHOR]