Tea polyphenols nanoparticles integrated with microneedles multifunctionally boost 5-aminolevulinic acid photodynamic therapy for skin cancer.

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor's inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs). The TP NPs specifically increase cellular uptake of ALA by A375 and A431 cells and reduce mitochondrial membrane potential. Subsequently, the photosensitizer protoporphyrin IX derived from ALA accumulates in the tumor cells in a dose-dependent manner with TP NPs, generating reactive oxygen species to promote apoptosis and necrosis of A375 and A431 cells. Interestingly, TP NPs can ameliorate the tumor's inherent hypoxia microenvironment and rapid oxygen consumption during PDT by inhibiting hypoxia inducible factor-1α, thereby boosting reactive oxygen species (ROS) generation and enhancing ALA-PDT efficacy through a positive feedback loop. After ALA@TP NPs are loaded into MNs to fabricate ALA@TP NPs@MNs, the MNs enhance skin penetration and storage stability of ALA. Importantly, they exhibit remarkable antitumor efficacy in A375-induced melanoma and A431-induced squamous cell carcinoma with a reduced dose of ALA and reverse hypoxia in vivo. This study provides a facile and novel strategy that integrates MNs and green NPs of TP for addressing the bottlenecks of ALA-PDT and enhancing the ALA-PDT efficacy against skin cancers for future clinical translation.

Type 2 Cytokine-Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study.

Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a noninvasive approach to investigate AD-derived KCs. To evaluate whether such AD-derived KCs are suitable to mimic AD inflammatory responses, we compared hair follicle-derived KCs from healthy donors with those from patients with AD in a type 2 cytokine environment. Stimulation of AD-derived KCs with IL-4 and IL-13 induced higher expression changes of AD-associated markers than that of healthy KCs. The combination of IL-4 and IL-13 generally induced highest expression changes, but IL-13 alone also induced significant changes of AD-specific markers. Similar to the 2-dimensional cultures, IL-4/IL-13 stimulation of 3-dimensional skin models generated with AD-derived KCs modulated the expression of several AD-relevant factors. Whole-transcriptome analysis revealed that IL-4 and IL-13 acted similarly on these 3-dimensional skin models. Histologically, IL-13 alone and in combination with IL-4 increased epidermal spongiosis, a histological hallmark of AD skin. Taken together, our pilot study suggests that hair follicle-derived KCs from patients with AD represent a useful model system to study AD-related inflammation in a personalized in vitro model.

Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study.

BACKGROUND: α1-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α1-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. METHODS: In a nationwide nested study, we identified 2702 individuals with α1-antitrypsin deficiency and 26,750 control subjects without α1-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. RESULTS: Individuals with α1-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81-2.63), leukemia (1.76, 1.12-2.79), liver cancer (3.91, 2.23-6.85), and cancer overall (1.25, 1.13-1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55-3.58), 1.83 (1.19-2.81), 4.46 (2.74-7.28), and 1.45 (1.31-1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60-4.95) and skin disease (2.93, 2.19-3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α1-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α1-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). CONCLUSION: Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.

The DNA sensor AIM2 mediates psoriasiform inflammation by inducing type 3 immunity.

Psoriasis is a chronic and recurrent inflammatory skin disease characterized by abnormal proliferation and differentiation of keratinocytes and activation of immune cells. However, the molecular driver that triggers this immune response in psoriatic skin remains unclear. The inflammation-related gene absent in melanoma 2 (AIM2) was identified as a susceptibility gene/locus associated with psoriasis. In this study, we investigated the role of AIM2 in the pathophysiology of psoriasis. We found elevated levels of mitochondrial DNA in patients with psoriasis, along with high expression of AIM2 in both the human psoriatic epidermis and a mouse model of psoriasis induced by topical imiquimod (IMQ) application. Genetic ablation of AIM2 reduced the development of IMQ-induced psoriasis by decreasing the production of type 3 cytokines (such as IL-17A and IL-23) and infiltration of immune cells into the inflammatory site. Furthermore, we demonstrate that IL-17A induced AIM2 expression in keratinocytes. Finally, the genetic absence of inflammasome components downstream AIM2, ASC, and caspase-1 alleviated IMQ-induced skin inflammation. Collectively, our data show that AIM2 is involved in developing psoriasis through its canonical activation.

Prevalence and gender - specific analysis of a systemic sclerosis cohort in Latvia.

BACKGROUND: Systemic sclerosis (SSc) is considered by many to be one of the most severe autoimmune rheumatic diseases with lower prevalence observed in Northern Europe. No previous studies on the prevalence of SSc in Latvia have been conducted and the aim was to study the demographic and clinical data of patients with SSc in northeastern Europe country. METHODS: This study was conducted in two main Latvian hospitals for adults and includes patients with SSc who were consulted between 2016 and 2021. RESULTS: During the study period, 159 patients with SSc were consulted. The point prevalence on 1 January 2021 was 84.0 per million. Female to male ratio was 4.67:1, and highest gender ratio was observed in the age group 70-79-year (6.75:1). Antinuclear antibodies were present in 82.58% of patients, without gender difference. Centromere pattern was more frequently observed in females (40.19% vs. 19.04%), in contrast to speckled pattern (50.98% vs. 57.14%). At disease onset females tended to be younger (46.51 ± 13.52) than males (50.5 ± 16.64). Males had more diffuse cutaneous subtype, interstitial lung disease, pulmonary hypertension and esophageal dysmotility. More than half of patients received treatment with glucocorticoids at any point of the disease (68.31%), without gender difference. CONCLUSIONS: Systemic sclerosis is less common in Latvia than in other countries and regions. Due to its location, the data from Latvia are consistent with a north-south gradient in Europe. Gender ratio differences persisted in older age groups as well. Antinuclear antibodies presence did not differ between genders, but in female's centromere pattern was much more likely to be present. Males had more severe disease course, but in both genders more than half of patients received treatment with GCs at any point of the disease.

The Use of Teledermatology for Skin Cancer Referrals: A Retrospective Study in a Single Tertiary Centre.

INTRODUCTION: Teledermatology utilises telecommunications technology to deliver dermatological care remotely, incorporating live video consultations, store-and-forward systems, and hybrid approaches. It is particularly valuable in underserved or remote areas with limited access to dermatologists. Reported benefits include reduced face-to-face consultations for benign lesions, leading to increased capacity for severe cases, improved access for rural patients, and enhanced satisfaction among clinicians and patients. The COVID-19 pandemic accelerated the adoption of teledermatology, integrating it into the National Health Service (NHS) framework for managing referrals and ensuring continuity of care. This study examines the outcomes of two-week wait referrals for suspected skin cancer, focusing on diagnostic concordance between teledermatology and histopathology. MATERIALS AND METHODS: The study was conducted at Addenbrooke's Hospital, part of Cambridge University Hospitals, via a retrospective review of patient records from November 2022 to May 2023. Inclusion criteria were all patients referred by their general practitioner (GP) under the two-week wait for suspected skin cancer pathway. Data collected included patient demographics, waiting times, clinical and histological diagnoses, and patient re-referrals for the same problem. The primary objective was to assess diagnostic concordance between the clinical diagnosis from teledermatology and histopathology. Secondary objectives included accuracy of lesion site description, patient waiting times, and computed time savings from the use of teledermatology. RESULTS: The study covered 71 patients (34 males, 37 females) aged 19-87 years (mean: 59.63), with Fitzpatrick skin I-III predominating. A total of 110 individual lesions were assessed, and 46 required surgical management. Clinical and histological concordance was 62%, with 100% accuracy for basal cell carcinoma (BCC) and melanoma. The service saved 10 hours of consultant time and reduced the need for 62 initial face-to-face consultations. Lesion site documentation had a 73% correlation between GPs and dermatologists. Diagnoses varied widely between GPs and dermatologists, with a 31% concordance. CONCLUSION: Our study shows that teledermatology is a safe and effective method for managing two-week wait referrals for suspected skin cancer, reducing footfall, and saving time and costs for both clinicians and patients. While there are limitations, the usage of teledermatology allows increasingly limited capacity for face-to-face consultations to be reserved for high-risk patients. Further studies in different regions should explore teledermatology's utility across diverse demographics, particularly to address healthcare disparities for those with darker skin tones.

Terlipressin-induced skin necrosis in cirrhotic patients-A case report and comprehensive literature review.

Key Clinical Message: The occurrence of terlipressin-induced skin necrosis in cirrhotic patients is a rare but serious adverse event that warrants further investigation. Clinicians should be aware of this potential complication in cirrhotic patients receiving terlipressin therapy and closely monitor for any signs of skin necrosis. Early recognition and prompt intervention are crucial in preventing further complications and improving patient outcomes. Further research is needed to better understand the risk factors associated with terlipressin-induced skin necrosis and to develop effective preventive strategies. Overall, healthcare providers should exercise caution when prescribing terlipressin to cirrhotic patients, weighing the potential benefits against the risks of this rare but significant adverse event. Abstract: Terlipressin is commonly used to manage conditions related to portal hypertension, such as hepatorenal syndrome and esophageal variceal bleeding. Despite its therapeutic benefits, terlipressin can rarely lead to severe ischemic complications involving the skin vasculature, known as terlipressin-induced skin necrosis. We present a 50-year-old male with cirrhosis and acute variceal bleeding who developed skin necrosis following terlipressin administration. We performed a comprehensive review of the literature by analyzing 18 case reports/case series comprising 22 cirrhotic patients with terlipressin-induced skin necrosis. Among these individuals, we found a mean age of 51 years with a male predominance (78%). Further analysis showed that the onset of skin necrosis ranged from 2 to 5 days post-terlipressin initiation, with bolus administration being predominant (85.7%). The underlying pathophysiological mechanisms of terlipressin-induced skin ischemia are still elusive but primarily attributed to the vasoconstrictive and thrombogenic effects. Management involves terlipressin discontinuation and supportive care. Physicians should be aware of this potential complication in patients receiving terlipressin and closely observe for any signs of skin rash.

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Introduction: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Materials and methods: Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Results: Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. Conclusion: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Blastic plasmacytoid dendritic cell neoplasm: Two case reports.

BACKGROUND: Blastic plasmacytoid dendritic cell tumor (BPDCN) is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells. BPDCN has an extremely poor prognosis. Skin lesions are usually the first manifestation of BPDCN, although the tumor may also invade the bone marrow, lymph nodes, peripheral blood, and other parts of the body, leading to several other manifestations, requiring further differentiation through skin biopsy and immunohistochemistry. CASE SUMMARY: In the present paper, the cases of 2 patients diagnosed with BPDCN are discussed. The immunohistochemistry analysis of these 2 patients revealed positivity for CD4, CD56, and CD123. Currently, no standard chemotherapy regimen is available for BPDCN. Therefore, intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases. CONCLUSION: Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable. Future treatment modalities tailored for elderly patients will help prolong survival.

A study of social isolation in patients with varicose veins of the lower extremities: A scoping review.

OBJECTIVES: To undertake a scoping review of the literature on social alienation in patients with lower extremity varicose veins in order to serve as a reference for future studies in the field. METHODS: With a focus on the phenomenon of social alienation in patients with varicose veins of the lower extremities, a systematic search of Chinese and English databases was carried out using the scoping review methodology as a framework. The included literature was summarized and analyzed with a time frame from database construction to June 24, 2024. RESULTS: A total of 15 publications were included, demonstrating that social alienation is a frequent occurrence in people with varicose veins of the lower extremities but has not yet received much attention. In individuals with varicose veins of the lower limbs, demographic factors, illness issues, psychological problems, and social factors are the key influences on social alienation. CONCLUSION: Social alienation is a common phenomenon that is unevenly distributed in patients with varicose veins of the lower leg and is influenced by a number of different circumstances. In order to better meet the social needs of patients, healthcare professionals should pay attention to the issue of social alienation in patients with varicose veins of the lower extremity, identify and implement intervention strategies quickly, and actively explore a new model of treatment and care for social alienation.

MobileNet-V2: An Enhanced Skin Disease Classification by Attention and Multi-Scale Features.

The increasing prevalence of skin diseases necessitates accurate and efficient diagnostic tools. This research introduces a novel skin disease classification model leveraging advanced deep learning techniques. The proposed architecture combines the MobileNet-V2 backbone, Squeeze-and-Excitation (SE) blocks, Atrous Spatial Pyramid Pooling (ASPP), and a Channel Attention Mechanism. The model was trained on four diverse datasets such as PH2 dataset, Skin Cancer MNIST: HAM10000 dataset, DermNet. dataset, and Skin Cancer ISIC dataset. Data preprocessing techniques, including image resizing, and normalization, played a crucial role in optimizing model performance. In this paper, the MobileNet-V2 backbone is implemented to extract hierarchical features from the preprocessed dermoscopic images. The multi-scale contextual information is fused by the ASPP model for generating a feature map. The attention mechanisms contributed significantly, enhancing the extraction ability of inter-channel relationships and multi-scale contextual information for enhancing the discriminative power of the features. Finally, the output feature map is converted into probability distribution through the softmax function. The proposed model outperformed several baseline models, including traditional machine learning approaches, emphasizing its superiority in skin disease classification with 98.6% overall accuracy. Its competitive performance with state-of-the-art methods positions it as a valuable tool for assisting dermatologists in early classification. The study also identified limitations and suggested avenues for future research, emphasizing the model's potential for practical implementation in the field of dermatology.

Potential association between allergenic food exposure and skin disease in Bangladesh: An application of principal component logistic regression (PCLR).

Background and Aim: Allergenic foods can trigger skin conditions, yet their impact in Bangladesh remains underexplored. This study aims to investigate the potential association between exposure to allergenic foods and the development of skin disease across Bangladesh. Methods: We conducted a cross-sectional survey with 970 respondents from the divisions of Dhaka, Sylhet, Rangpur, and Chattogram who self-reported skin disease triggered by food allergens. We analyzed the data using multiple response analysis and principal component logistic regression. Results: Approximately 64% of respondents had skin disease attributable to allergenic foods, with a relatively higher proportion among females (52%) than males (48%). Beef (67%), Brinjal (47.1%), Hilsa (45.8%), and Shrimp (23.7%) were the most frequently cited allergenic foods. Principal component logistic regression identified two highly significant principal components: the first representing Hilsa, Beef, and Brinjal (odds ratio = 2.256), and the sixth reflecting Corn (odds ratio = 1.342). Individuals who consumed foods with high loadings of the first principal component were 125.6% more likely to develop skin disease than nonconsumers, while those exposed to Corn had a 34.2% higher risk. Conclusion: The findings highlight prevalent allergenic foods in Bangladesh and their substantial impact on skin health, underscoring the need for dietary awareness and tailored interventions to mitigate allergic skin conditions in this population.

Machine learning-based identification of an immunotherapy-related signature to enhance outcomes and immunotherapy responses in melanoma.

Background: Immunotherapy has revolutionized skin cutaneous melanoma treatment, but response variability due to tumor heterogeneity necessitates robust biomarkers for predicting immunotherapy response. Methods: We used weighted gene co-expression network analysis (WGCNA), consensus clustering, and 10 machine learning algorithms to develop the immunotherapy-related gene model (ITRGM) signature. Multi-omics analyses included bulk and single-cell RNA sequencing of melanoma patients, mouse bulk RNA sequencing, and pathology sections of melanoma patients. Results: We identified 66 consensus immunotherapy prognostic genes (CITPGs) using WGCNA and differentially expressed genes (DEGs) from two melanoma cohorts. The CITPG-high group showed better prognosis and enriched immune activities. DEGs between CITPG-high and CITPG-low groups in the TCGA-SKCM cohort were analyzed in three additional melanoma cohorts using univariate Cox regression, resulting in 44 consensus genes. Using 101 machine learning algorithm combinations, we constructed the ITRGM signature based on seven model genes. The ITRGM outperformed 37 published signatures in predicting immunotherapy prognosis across the training cohort, three testing cohorts, and a meta-cohort. It effectively stratified patients into high-risk or low-risk groups for immunotherapy response. The low-risk group, with high levels of model genes, correlated with increased immune characteristics such as tumor mutation burden and immune cell infiltration, indicating immune-hot tumors with a better prognosis. The ITRGM's relationship with the tumor immune microenvironment was further validated in our experiments using pathology sections with GBP5, an important model gene, and CD8 IHC analysis. The ITRGM also predicted better immunotherapy response in eight cohorts, including urothelial carcinoma and stomach adenocarcinoma, indicating broad applicability. Conclusions: The ITRGM signature is a stable and robust predictor for stratifying melanoma patients into 'immune-hot' and 'immune-cold' tumors, enhancing prognosis and response to immunotherapy.

Biomaterials for reliable wearable health monitoring: Applications in skin and eye integration.

Recent advancements in biomaterials have significantly impacted wearable health monitoring, creating opportunities for personalized and non-invasive health assessments. These developments address the growing demand for customized healthcare solutions. Durability is a critical factor for biomaterials in wearable applications, as they must withstand diverse wearing conditions effectively. Therefore, there is a heightened focus on developing biomaterials that maintain robust and stable functionalities, essential for advancing wearable sensing technologies. This review examines the biomaterials used in wearable sensors, specifically those interfaced with human skin and eyes, highlighting essential strategies for achieving long-lasting and stable performance. We specifically discuss three main categories of biomaterials-hydrogels, fibers, and hybrid materials-each offering distinct properties ideal for use in durable wearable health monitoring systems. Moreover, we delve into the latest advancements in biomaterial-based sensors, which hold the potential to facilitate early disease detection, preventative interventions, and tailored healthcare approaches. We also address ongoing challenges and suggest future directions for research on material-based wearable sensors to encourage continuous innovation in this dynamic field.

Optimization of skin sampling based on tape stripping for lipidome analysis by nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry.

In this study, skin sampling by tape stripping for lipid analysis was optimized by examining the lipid profiles of the stratum corneum (SC), focusing on the composition and levels of ceramides (Cer), diacylglycerols (DG), and triacylglycerols (TG), using nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry. Significant variations in the number and composition of the identified lipids, particularly Cer and neutral lipid species, were observed across different skin locations, including the forearm, forehead, cheek, and neck. Analysis of the layer-to-layer lipid profiles of the seven consecutive layers revealed a gradual decrease in DG and TG levels from the outermost to the innermost layers, with certain Cer subclasses showing increases in the second to fourth layers and subsequent decreases. Comparative analysis of lipid profiles from adjacent spots demonstrated statistical consistency and persistent differences between spots. Pooling layers were evaluated as an alternative method for representing SC layers, and their efficiencies were assessed by varying the number of pooled layers. We found that pooling five consecutive layers was effective in terms of the number and levels of identified lipids. Additionally, investigations into the matrix effect and extraction efficiency upon pooling layers indicated that pooling up to five layers did not significantly affect ionization suppression or reduce extraction recovery.

Time from Diagnostic Suspicion to In-Person Evaluation in Skin Cancer Using Teledermatology.

Introduction: Early diagnosis of skin cancer is crucial for improving prognosis. Teledermatology (TD) usage can optimize referrals and reduce waiting times. This study aims to evaluate waiting times at the critical referral nodes in teleinterconsultations that raised suspicion of skin malignancy in the Chilean TD platform of the public health care system. Materials and Methods: A cross-sectional observational study that analyzed asynchronous teleinterconsultations and raised suspicion for skin malignancy following the teledermatologist evaluation was uploaded on the Chilean Ministry of Health's TD platform from January 1 to June 30, 2022. Results: Out of 20,522 teleinterconsultations, 1,853 raised suspicion of skin cancer. Among them, 1,119 patients were assessed by in-person examination, while 669 were still on the waiting list. Response times averaged 3.98 days for TD diagnostic suggestions. Overall referral times averaged 75.98 days from initial teleinterconsultation to the final specialist in-person evaluation. Waiting times showed significant differences among health care services and geographic regions. Discussion: In resource-limited settings, TD serves as a valuable tool to optimize referrals and manage the demand for oncologic dermatological consultation. The long waiting times emphasize the need for targeted interventions, especially in regions with longer delays. Conclusion: While TD has shown to be an effective tool in optimizing referrals, waiting times still exceed international recommendations, even in urban centers. The considerable heterogeneity in referral times within health care services and geographic regions highlights the necessity of establishing standardized referral protocols and explicit deadlines to fulfill teleinterconsultations that raise suspicion of skin malignancy in the Chilean public system.

A Descriptive, Post Hoc Analysis of Efficacy and Safety of Risankizumab in Diverse Racial and Ethnic Patient Populations With Moderate-to-Severe Psoriasis.

INTRODUCTION: Historically, patients with skin of color are underdiagnosed with psoriasis and underrepresented in clinical trials. In this study, we assess the efficacy and safety of risankizumab in patients with moderate-to-severe plaque psoriasis by race and ethnicity in the open label extension LIMMitless (NCT03047395). METHODS: Patients received continuous treatment with 150 mg risankizumab through their initial trial and the open label extension. Patients self-identified their race and ethnicity. Efficacy was assessed using Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety is reported by events/100 patient-years. RESULTS: A total of 897 patients (race: 662 White, 196 Asian, 25 Black or African American, 14 Other; ethnicity: 98 Hispanic or Latino, 799 non-Hispanic or Latino) were included in this analysis. Compared to baseline, patients had a mean percent reduction in PASI between 94.6% (Asian) and 99.3% (Black or African American) and reported mean percent improvements in DLQI ranging from 87.1% (Asian and Black or African American) to 93.7% (Hispanic or Latino) at week 100. CONCLUSION: While the data presented here comprise a small retrospective descriptive analysis and cannot detect statistical differences, efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis appears similar across the racial and ethnic groups studied and no new safety signals were detected.

In vitro 3D skin culture and its sustainability in toxicology: a narrative review.

In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.