A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children.

Atopic dermatitis (AD), a common pruritic and chronic inflammatory skin disease, has a major impact on a patient's quality of life. It is characterized by dry, itchy, and eczema-like rashes. AD is more prevalent in young children and has been linked to a variety of other allergy disorders. Traditional drug therapy has certain limitations for treating young children with AD. However, biologics have good clinical application prospects in the medical treatment of young patients. Dupilumab, a fully human monoclonal antibody, specifically binds to the IL-4 Rα subunit, inhibiting IL-4 and IL-13 signaling and blocking the occurrence of type 2 inflammatory response. It has a good effect on treating infants and children with moderate-to-severe AD. This review explores the safety and efficacy of dupilumab in the treatment of AD in infants and children and the impact of early intervention on AD progression, with the aim of informing clinical practice in the use of dupilumab for the treatment of young patients with AD.

Using machine learning techniques to predict the risk of osteoporosis based on nationwide chronic disease data.

Osteoporosis is a major public health concern that significantly increases the risk of fractures. The aim of this study was to develop a Machine Learning based predictive model to screen individuals at high risk of osteoporosis based on chronic disease data, thus facilitating early detection and personalized management. A total of 10,000 complete patient records of primary healthcare data in the German Disease Analyzer database (IMS HEALTH) were included, of which 1293 diagnosed with osteoporosis and 8707 without the condition. The demographic characteristics and chronic disease data, including age, gender, lipid disorder, cancer, COPD, hypertension, heart failure, CHD, diabetes, chronic kidney disease, and stroke were collected from electronic health records. Ten different machine learning algorithms were employed to construct the predictive mode. The performance of the model was further validated and the relative importance of features in the model was analyzed. Out of the ten machine learning algorithms, the Stacker model based on Logistic Regression, AdaBoost Classifier, and Gradient Boosting Classifier demonstrated superior performance. The Stacker model demonstrated excellent performance through ten-fold cross-validation on the training set and ROC curve analysis on the test set. The confusion matrix, lift curve and calibration curves indicated that the Stacker model had optimal clinical utility. Further analysis on feature importance highlighted age, gender, lipid metabolism disorders, cancer, and COPD as the top five influential variables. In this study, a predictive model for osteoporosis based on chronic disease data was developed using machine learning. The model shows great potential in early detection and risk stratification of osteoporosis, ultimately facilitating personalized prevention and management strategies.

Construction and validation of a machine learning model for the diagnosis of juvenile idiopathic arthritis based on fecal microbiota.

Purpose: Human gut microbiota has been shown to be significantly associated with various inflammatory diseases. Therefore, this study aimed to develop an excellent auxiliary tool for the diagnosis of juvenile idiopathic arthritis (JIA) based on fecal microbial biomarkers. Method: The fecal metagenomic sequencing data associated with JIA were extracted from NCBI, and the sequencing data were transformed into the relative abundance of microorganisms by professional data cleaning (KneadData, Trimmomatic and Bowtie2) and comparison software (Kraken2 and Bracken). After that, the fecal microbes with high abundance were extracted for subsequent analysis. The extracted fecal microbes were further screened by least absolute shrinkage and selection operator (LASSO) regression, and the selected fecal microbe biomarkers were used for model training. In this study, we constructed six different machine learning (ML) models, and then selected the best model for constructing a JIA diagnostic tool by comparing the performance of the models based on a combined consideration of area under receiver operating characteristic curve (AUC), accuracy, specificity, F1 score, calibration curves and clinical decision curves. In addition, to further explain the model, Permutation Importance analysis and Shapley Additive Explanations (SHAP) were performed to understand the contribution of each biomarker in the prediction process. Result: A total of 231 individuals were included in this study, including 203 JIA patients and Non-JIA individuals. In the analysis of diversity at the genus level, the alpha diversity represented by Shannon value was not significantly different between the two groups, while the belt diversity was slightly different. After selection by LASSO regression, 10 fecal microbe biomarkers were selected for model training. By comparing six different models, the XGB model showed the best performance, which average AUC, accuracy and F1 score were 0.976, 0.914 and 0.952, respectively, thus being used to construct the final JIA diagnosis model. Conclusion: A JIA diagnosis model based on XGB algorithm was constructed with excellent performance, which may assist physicians in early detection of JIA patients and improve the prognosis of JIA patients.

Treatment With Selumetinib for Café-au-Lait Macules and Plexiform Neurofibroma in Pediatric Patients With Neurofibromatosis Type 1.

This case report describes 4 patients with a rare autosomal dominant multisystem disorder resulting from NF1 variants that leads to café-au-lait macules and neurofibromas.

Integrated single-cell and spatial transcriptomics reveals heterogeneity of fibroblast and pivotal genes in psoriasis.

Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis.

Narrative Review of the Pathogenesis of Stasis Dermatitis: An Inflammatory Skin Manifestation of Venous Hypertension.

INTRODUCTION: Stasis dermatitis (SD), also known as venous dermatitis, is a form of inflammatory dermatitis of the lower extremities that typically occurs in older individuals and represents a cutaneous manifestation of venous hypertension. Venous hypertension (also known as sustained ambulatory venous pressure) is most often due to retrograde blood flow, which occurs due to calf muscle pump failure. This failure is most commonly secondary to incompetent venous valves, valve destruction, or obstruction of the venous system. Many of the common symptoms associated with SD are caused by inflammatory processes. METHODS: This review summarizes the pathogenesis and key role of inflammation in SD by reviewing inflammatory biomarkers associated with SD. The literature was selected though a high-level PubMed search focusing on keywords relating to inflammation associated with SD. RESULTS: Venous reflux at the lower extremities causes venous hypertension, which leads to chronic venous insufficiency. High venous pressure due to venous hypertension promotes the local accumulation and extravasation of inflammatory cells across the vascular endothelium. Leukocyte trapping in the microcirculation and perivascular space is associated with trophic skin changes. Cell adhesion molecules are linked with the perpetuated influx of activated leukocytes into inflammatory sites. Here, inflammatory cells may influence the remodeling of the extracellular matrix by inducing the secretion of proteinases such as matrix metalloproteinases (MMPs). The increased expression of MMPs is associated with the formation of venous leg ulcers and lesions. Phosphodiesterase 4 activity has also been shown to be elevated in individuals with inflammatory dermatoses compared to healthy individuals. DISCUSSION: Because inflammation is a key driver of the signs and symptoms of SD, several of the highlighted biomarkers of inflammation represent potential opportunities to target and interrupt molecular pathways of cutaneous inflammation and, therefore, remediate the signs and symptoms of SD. CONCLUSION: Understanding the pathogenesis of SD may help clinicians identify drivers of inflammation to use as potential targets for the development of new treatment options.

Stasis dermatitis is a skin disease that affects the legs, most often of older people, with chronic venous insufficiency. Chronic venous insufficiency is when veins cannot return blood from the legs back to the heart. This leads to high blood pressure in veins and causes blood in those veins to flow backwards. If stasis dermatitis is left untreated, complications, including skin ulcers, can result. Other skin symptoms of stasis dermatitis include itchiness, scaling, and discoloration. Such skin symptoms can have a negative effect on a person's quality of life. Inflammation that lasts a long time is likely the main link between the skin changes seen in people with stasis dermatitis and the increased pressure in leg veins. Several molecules are associated with the inflammation observed in stasis dermatitis, including white blood cells, matrix metalloproteinases, phosphodiesterase 4, and interleukin-31. Treatment for stasis dermatitis should focus both on the underlying chronic venous insufficiency and the associated skin issues. Identifying inflammatory markers and pathways could help treat the signs and symptoms associated with stasis dermatitis, including the skin symptoms.

Advances in machine learning-based bacteria analysis for forensic identification: identity, ethnicity, and site of occurrence.

When faced with an unidentified body, identifying the victim can be challenging, particularly if physical characteristics are obscured or masked. In recent years, microbiological analysis in forensic science has emerged as a cutting-edge technology. It not only exhibits individual specificity, distinguishing different human biotraces from various sites of occurrence (e.g., gastrointestinal, oral, skin, respiratory, and genitourinary tracts), each hosting distinct bacterial species, but also offers insights into the accident's location and the surrounding environment. The integration of machine learning with microbiomics provides a substantial improvement in classifying bacterial species compares to traditional sequencing techniques. This review discusses the use of machine learning algorithms such as RF, SVM, ANN, DNN, regression, and BN for the detection and identification of various bacteria, including Bacillus anthracis, Acetobacter aceti, Staphylococcus aureus, and Streptococcus, among others. Deep leaning techniques, such as Convolutional Neural Networks (CNN) models and derivatives, are also employed to predict the victim's age, gender, lifestyle, and racial characteristics. It is anticipated that big data analytics and artificial intelligence will play a pivotal role in advancing forensic microbiology in the future.

Investigation of optimal energy or density of a fractional CO2 laser system in the treatment of stable non-segmental vitiligo.

BACKGROUND: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo. OBJECTIVE: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients. METHOD: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd). RESULTS: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05). CONCLUSION: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%.

Clinical guideline for the diagnosis and treatment of cutaneous warts (2022).

AIM: Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed. METHODS: We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%. RESULTS: Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained. CONCLUSIONS: It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Effects of Oral Carotenoids on Oxidative Stress: A Systematic Review and Meta-Analysis of Studies in the Recent 20 Years.

Carotenoids protect organs, tissues, and cells from the damaging action of singlet oxygen, oxygen radicals, and lipid peroxides. This systematic review was sought to evaluate the influence of oral carotenoids on antioxidant/oxidative markers, blood carotenoids levels, and lipid/lipoprotein parameters in human subjects. A comprehensive review of relevant literature was conducted in PubMed, Web of Sciences, and the Cochrane library, from 2000 to December 2020. Randomized controlled trials, case-controlled trials, or controlled trials were identified. A total of eighteen trials were included, with the target populations being healthy subjects in 16 studies, athletes in 1 study, and pregnant women in 1 study. The meta-analysis results showed that carotenoids complex supplementation significantly increased the levels of antioxidative parameters ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) [standardized mean difference (SMD) = 0.468; 95% CI: 0.159-0.776, p = 0.003; SMD = 0.568; 95% CI: 0.190-0.947, p = 0.003] and decreased the blood triglyceride (TG) level (SMD = -0.410, 95% CI: -0.698 to -0.122, p = 0.005). Oral carotenoids supplement significantly increased the blood levels of ß-carotene (SMD = 0.490, 95% CI: 0.123-0.858, p = 0.009), α-tocopherol (SMD = 0.752, 95%CI: 0.020-1.485, p = 0.044), and the intaking durations were 8 weeks. The levels of antioxidative enzymes and other lipid/lipoprotein parameters were not different between subjects receiving carotenoids and controls (p > 0.05). In conclusion, our systematic review showed that the carotenoids complex is beneficial for alleviating potential oxidative stress via interacting with free radicals or decreasing blood TG levels. The intaking duration of carotenoids should be 8 weeks to reach enough concentration for function.

Sporothrix schenckii regulates macrophage inflammatory responses via the c-JUN-induced Dab2 transcription.

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2-like type of gene expression in BMDMs with the inhibited Il-6, Il1-ß and Arg-1 and induced Tnf-α, Il-10 and Mgl-1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN. We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis-induced skin lesions were accompanied with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c-JUN pathway, effects that can then control the expression of inflammatory factors.

Experts' Consensus on the Use of Pimecrolimus in Atopic Dermatitis in China: A TCS-Sparing Practical Approach.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease with rising prevalence. Topical corticosteroids (TCS) are recommended as first-line therapy for patients with AD in China; however, corticophobia is a widespread concern, which can manifest as noncompliance: in a previous Chinese study, almost all parents whose children had AD were very concerned about the side effects of TCS and, as a result, nearly half did not use it in the event of recurrence. We propose a TCS-sparing treatment algorithm for the management of infants, children, adolescents, and adults with mild-to-moderate AD, to guide clinical practice in China. METHODS: A panel of eight experts in AD from China and one expert from Germany formed to develop a practical algorithm for the management of mild-to-moderate AD, focusing on pimecrolimus. RESULTS: Irrespective of body location, all patients with mild AD (including acute flares) and infants with moderate AD should apply the topical calcineurin inhibitor (TCI) pimecrolimus twice daily to the affected area until symptoms disappear. For children, adolescents, and adults with moderate AD, pimecrolimus should be applied twice daily to sensitive skin areas, and a TCI (either pimecrolimus or tacrolimus) should be applied twice daily to other body locations. Short-term administration of TCS, followed by TCI twice daily, is recommended for most patients with moderate AD experiencing acute flares, regardless of lesion site. Emollients should be used regularly. CONCLUSIONS: The algorithm presented intends to simplify treatment of AD in China and guide clinical decision-making.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.