Multiple Skin Research Articles

Unveiling the mechanisms for the development of rosehip-based dermatological products: an updated review.

Rosa spp., commonly known as rosehips, are wild plants that have traditionally been employed as herbal remedies for the treatment of a wide range of disorders. Rosehip is a storehouse of vitamins, including A, B complex, C, and E. Among phytonutrients, vitamin C is found in the highest amount. As rosehips contain significant levels of vitamin C, they are perfect candidates for the development of skincare formulations that can be effectively used in the treatment of different skin disorders (i.e., scarring, anti-aging, hyperpigmentation, wrinkles, melasma, and atopic dermatitis). This research focuses on the vitamin C content of several Rosa sp. by their botanical and geographic origins, which according to research studies are in the following order: R. rugosa > R. montana > R. canina > R. dumalis, with lower levels in R. villosa and R. arvensis, respectively. Among rosehip species, R. canina is the most extensively studied species which also displays significant amounts of bioactive compounds, but also antioxidant, and antimicrobial activities (e.g., against Propionibacterium acnes, Staphylococcus aureus, S, epidermis, and S. haemolyticus). The investigation also highlights the use of rosehip extracts and oils to minimise the harmful effects of acne, which primarily affects teenagers in terms of their physical appearance (e.g., scarring, hyperpigmentation, imperfections), as well as their moral character (e.g., low self-confidence, bullying). Additionally, for higher vitamin C content from various rosehip species, the traditional (i.e., infusion, maceration, Soxhlet extraction) and contemporary extraction methods (i.e., supercritical fluid extraction, microwave-assisted, ultrasonic-assisted, and enzyme-assisted extractions) are highlighted, finally choosing the best extraction method for increased bioactive compounds, with emphasis on vitamin C content. Consequently, the current research focuses on assessing the potential of rosehip extracts as medicinal agents against various skin conditions, and the use of rosehip concentrations in skincare formulations (such as toner, serum, lotion, and sunscreen). Up-to-date studies have revealed that rosehip extracts are perfect candidates as topical application products in the form of nanoemulsions. Extensive in vivo studies have revealed that rosehip extracts also exhibit specific activities against multiple skin disorders (i.e., wound healing, collagen synthesis, atopic dermatitis, melasma, and anti-aging effects). Overall, with multiple dermatological actions and efficacies, rosehip extracts and oils are promising agents that require a thorough investigation of their functioning processes to enable their safe use in the skincare industry.

MICIL: Multiple-Instance Class-Incremental Learning for skin cancer whole slide images

Artificial intelligence (AI) agents encounter the problem of catastrophic forgetting when they are trained in sequentially with new data batches. This issue poses a barrier to the implementation of AI-based models in tasks that involve ongoing evolution, such as cancer prediction. Moreover, whole slide images (WSI) play a crucial role in cancer management, and their automated analysis has become increasingly popular in assisting pathologists during the diagnosis process. Incremental learning (IL) techniques aim to develop algorithms capable of retaining previously acquired information while also acquiring new insights to predict future data. Deep IL techniques need to address the challenges posed by the gigapixel scale of WSIs, which often necessitates the use of multiple instance learning (MIL) frameworks. In this paper, we introduce an IL algorithm tailored for analyzing WSIs within a MIL paradigm. The proposed Multiple Instance Class-Incremental Learning (MICIL) algorithm combines MIL with class-IL for the first time, allowing for the incremental prediction of multiple skin cancer subtypes from WSIs within a class-IL scenario. Our framework incorporates knowledge distillation and data rehearsal, along with a novel embedding-level distillation, aiming to preserve the latent space at the aggregated WSI level. Results demonstrate the algorithm’s effectiveness in addressing the challenge of balancing IL-specific metrics, such as intransigence and forgetting, and solving the plasticity-stability dilemma.

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris.

The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms. We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions. The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses. These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

Abstract 6988: TP53RK regulates DNA replication by CDC7-mediated MCM helicase phosphorylation in colorectal cancer

Abstract Background: We identify TP53 regulating kinase (TP53RK), which showed the highest cell growth inhibition efficiency in six colon cancer cell lines. TP53RK is overexpressed in various cancer types, including multiple myeloma and skin cancer, but the mechanism for its tumorigenesis in colon cancer is unknown. Therefore, this study aims to reveal the tumorigenesis mechanism of TP53RK, which is overexpressed in Colorectal Cancer (CRC), through global and phospho-proteomics. Method: A total 5 CRC cell lines (HT29, SW480, HCT116, H508 and CaCO2), colon normal fibroblast CRL1459, HCT116 p53 null cell and patient-derived normal organoid were used. Immunoblotting, MTT assay, Colony formation assay, Annexin-V assay and cell cycle analysis were performed for evaluation of TP53RK loss-of-function. With kinase-substrate enrichment analysis with phospho-proteome analysis, MCM2 was found to be a substrate for the kinase regulated by TP53RK. Results: High-throughput genetic screening approach have been widely applied to the study the gene function and molecular mechanism associated with tumorigenesis. By using genome-wide CRISPR/Cas9 library screening, we identify TP53RK, the first committed negative-selected gene, as a tyrosine kinase in the colorectal cancer(CRC) specific biomarker. Through proteome analysis, we found that depletion of TP53RK can hypo-phosphorylate the DNA helicase complex, MCM2 (minichromosome maintenance protein2). According to previous studies, the phosphorylation of MCM2 is regulated by CDC7 (cell division cycle7), and the abnormal states of CDC7 and MCM2 cause DNA replication disorder. Our results show that TP53RK expression is upregulated in CRC and its depletion results in decreased CDC7 expression and hypo-phosphorylation of the MCM complex. Decreased CDC7 expression due to its instability after TP53RK depletion can lead to DNA replication errors. DNA replication errors can lead cancer cells to apoptosis, suggesting that they may be a strategy for cancer treatment. In summary, we provide TP53RK as a novel prognostic and therapeutic target in CRC. Conclusion: To recapitulate briefly, our findings suggest that the interaction of TP53RK with CDC7 can regulate CDC7 protein stability and stabilized CDC7 can phosphorylate MCM2 to initiate DNA replication. In other words, because overexpression of TP53RK acts as an oncogene that promotes tumor progression in CRC, depletion of TP53RK can degrade CDC7 and induce colon cancer cells to death or regression. Citation Format: Younghee Choi, Ji-won Park, Jun-kyu Kang, Eun-ju Kim, Sang-Hyun Song, Eugene C. Yi, Tae-You Kim. TP53RK regulates DNA replication by CDC7-mediated MCM helicase phosphorylation in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6988.

Abstract 4484: Discovery of a potential first-in-class Za targeted small molecule inhibitor of ADAR1 p150 which demonstrates strong anti-tumor efficacy

Abstract Background: Adenosine deaminase, RNA specific (ADAR1), catalyzes the hydrolytic deamination of adenosine (A) to inosine (I) in double-stranded (ds) RNAs. ADAR1 has two isoforms: p110 in the nucleus and p150 in the cytoplasm. Both isoforms alter the coding and non-coding sections of self-dsRNA. The ADAR1 p150 isoform is expressed from an interferon (IFN)-response promoter and has a Z-DNA/Z-RNA binding domain at the N-terminus. ADAR1 has been implicated in promoting cell survival and resistance to immune response in several cancer types like multiple myeloma, breast, lung, liver, and skin cancer. Inhibition of ADAR1 p150 has the potential to enhance anti-tumor efficacy as monotherapy and in combination with other therapeutic modalities. The Zα domain of ADAR1 p150 provides exclusivity to p150 compared to the other isoforms. Herein, we outline the discovery of a potential first-in-class Zα targeted ADAR1 p150 inhibitor and degrader for cancer immunotherapy. Methods: AVA-ADR-001 was identified through a high throughput p110 knockout cell-based assay. The ability of AVA-ADR-001 to induce interferons was confirmed in various cell lines. The anti-tumor efficacy of AVA-ADR-001 was evaluated in B16F10 syngeneic melanoma mice model as monotherapy and in combination with anti-PD-1. PROTAC AVA-ADR-703 was used to demonstrate selective degradation of the ADAR1 p150 protein. Results: We have discovered AVA-ADR-001, a novel small molecule inhibitor of ADAR1 which significantly increases the IFN response in vitro in an MDA5-dependent manner. In vitro binding studies confirm that AVA-ADR-001 binds to the Zα domain of ADAR1 with low nM potency. AVA-ADR-001 demonstrates anti-tumor efficacy 1.5X superior to anti-PD1 ICB non-responsive tumor models. In addition, the AVA-ADR-001 monotherapy and combination groups showed a significant upregulation of numerous interferon-stimulated genes, including IFIH1, IFN-β, and CXCL-10. Finally, targeted protein degradation of ADAR1 p150 while sparing ADAR1 p110 was confirmed when cells were treated with AVA-ADR-703 with nM DC50, the PROTAC variant of AVA-ADR-001. Conclusions: To our knowledge, AVA-ADR-001 and AVA-ADR-703 are the first selective Zα-targeted small molecule inhibitor and degrader of ADAR1 p150 respectively to be disclosed. As a powerful and targeted first-in-class ADAR1 inhibitor, AVA-ADR-001 has demonstrated a strong induction of interferon (IFN) in a number of cancer cell lines and in vivo. AVA-ADR-001 has also demonstrated strong in vivo anti-tumor efficacy as monotherapy and in combination with anti-PD1. Furthermore, AVA-ADR-703 demonstrates selective and highly efficient degradation of ADAR1 p150 while sparing ADAR1 p110. Given that ADAR1 has a pro-metastatic and immune-suppressive role, AVA-ADR-001 and AVA-ADR-703 have significant potential to emerge as strong cancer immunotherapy candidates. Citation Format: Avijit Goswami, Sandeep Goyal, Kawaljit Singh, Princy Khurana, Barnali Deb, Aditya Kulkarni. Discovery of a potential first-in-class Za targeted small molecule inhibitor of ADAR1 p150 which demonstrates strong anti-tumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4484.

Differentiation of keratinocytes or exposure to type 2 cytokines diminishes S. aureus internalization.

Staphylococcus aureus is a leading cause of skin and soft tissue infections. Colonization by this bacterium is increased in individuals with chronic cutaneous diseases such as atopic dermatitis, psoriasis, and bullous pemphigoid. The greater abundance of S. aureus on the skin of subjects with atopic dermatitis in particular has been linked to recurrent cutaneous infections. The primary cell type of the epidermal layer of the skin is the keratinocyte, and it is thought that S. aureus internalized in keratinocytes associates with an increased incidence of skin infections. This study addresses whether keratinocyte differentiation and/or inflammation, two important characteristics altered in cutaneous diseases, influence bacterial internalization. To do this, S. aureus internalization was measured in immortalized and primary keratinocytes that were differentiated using high Ca2+-containing media and/or exposed to cytokines characteristic of atopic dermatitis (IL-4 and IL-13) or psoriasis (IL-17A and IL-22) skin. Our results indicate that S. aureus internalization is uniquely decreased upon keratinocyte differentiation, since this was not observed with another skin-resident bacterium, S. epidermidis. Additionally, treatment with IL-4 + IL-13 diminished bacterial internalization. We interpret this decrease as a mechanism of keratinocyte-based bacterial killing since a similar number of bacterial genomes were detected in cytokine-treated cells, but less viable internalized S. aureus was recovered. Finally, of the receptors reported for S. aureus binding/internalizing into keratinocytes, expression of the α5 component of the α5β1 integrin was in greatest accordance with the number of internalized bacteria in the context of keratinocyte differentiation.IMPORTANCEIndividuals with chronic cutaneous diseases demonstrate heightened susceptibility for severe and recurrent infections from Staphylococcus aureus. What drives this altered susceptibility remains poorly understood. Previous publications have detected S. aureus as deep as the dermal layer of skin in subjects with atopic dermatitis, suggesting that the cutaneous environment of this disease enables deeper bacterial infiltration than occurs in healthy individuals. This observation indicates that S. aureus has greater opportunity to interact with multiple skin cell types in individuals with chronic inflammatory skin diseases. Identifying the characteristics of the skin that influence bacterial internalization, a common method to establish reservoirs and evade the immune response, is critical for our understanding of S. aureus pathogenesis. The significance of this research is the novel identification of epidermal characteristics that influence S. aureus internalization. With this knowledge, methods can be developed to identify patient populations at greater risk for cutaneous infections.

An unusual case of multiple skin abscesses caused by methicillin-resistant <i>Staphylococcus aureus </i>in a 6-year-old boy

This report is a rare case of a 6-year-old child presenting with multiple skin abscesses resulting from a methicillin-resistant Staphylococcus aureus (MRSA) infection post blunt trauma to the pelvic region. Staphylococcus aureus poses challenges due to its antibiotic resistance. The child’s condition, marked by sepsis and extensive abscesses, prompted a multidisciplinary approach involving antibiotic therapy and surgical interventions. The MRSA strain exhibited resistance to various antibiotics, emphasizing the importance of individualized treatment as per the case. The case underlines the complexities of managing multi-site MRSA infections and emphasizes the significance of accurate diagnosis, appropriate antibiotic selection, and surgical intervention for successful outcomes.

Illegal wildlife trade: An analysis of carnivore products found in markets in Benin and Niger

West Africa is home to one of the largest protected area systems in Africa, the W-Arly- Pendjari (WAP) Complex, which provides a last refuge for many threatened carnivore species extirpated from most other protected areas in the region. However, rising global demand for wildlife products has increased concerns about the impacts of Illegal Wildlife Trade (IWT) on these species. To assess the extent of IWT, covert market surveys were conducted in Benin and Niger to identify wildlife products and derivatives coming from carnivore species (African civet, serval, caracal, lion, cheetah, leopard, and spotted hyena) suspected to be targeted by IWT. When possible, information about product origin was gathered to understand trading routes. Data were analysed to determine if products were available in markets due to their proximity to source populations or due to accessibility to trade and transport hubs. A variety of products from several threatened species, including multiple lion skins, were found in Benin and Niger. Products were found more frequently in markets near the WAP Complex and main trade and transport hubs. Sellers reported that a large majority of products originated from international trade, but some could also have been sourced from the WAP Complex. There was little evidence indicating that product availability was more affected by the distance to the WAP Complex than by the distance to international transport hubs, suggesting that trade was widespread across both countries. The study provides an evidence base and monitoring baselines to identify and assess interventions to address IWT and ultimately reduce illegal trafficking of wildlife.

LAMA: Lesion-Aware Mixup Augmentation for Skin Lesion Segmentation.

Deep learning can exceed dermatologists' diagnostic accuracy in experimental image environments. However, inaccurate segmentation of images with multiple skin lesions can be seen with current methods. Thus, information present in multiple-lesion images, available to specialists, is not retrievable by machine learning. While skin lesion images generally capture a single lesion, there may be cases in which a patient's skin variation may be identified as skin lesions, leading to multiple false positive segmentations in a single image. Conversely, image segmentation methods may find only one region and may not capture multiple lesions in an image. To remedy these problems, we propose a novel and effective data augmentation technique for skin lesion segmentation in dermoscopic images with multiple lesions. The lesion-aware mixup augmentation (LAMA) method generates a synthetic multi-lesion image by mixing two or more lesion images from the training set. We used the publicly available International Skin Imaging Collaboration (ISIC) 2017 Challenge skin lesion segmentation dataset to train the deep neural network with the proposed LAMA method. As none of the previous skin lesion datasets (including ISIC 2017) has considered multiple lesions per image, we created a new multi-lesion (MuLe) segmentation dataset utilizing publicly available ISIC 2020 skin lesion images with multiple lesions per image. MuLe was used as a test set to evaluate the effectiveness of the proposed method. Our test results show that the proposed method improved the Jaccard score 8.3% from 0.687 to 0.744 and the Dice score 5% from 0.7923 to 0.8321 over a baseline model on MuLe test images. On the single-lesion ISIC 2017 test images, LAMA improved the baseline model's segmentation performance by 0.08%, raising the Jaccard score from 0.7947 to 0.8013 and the Dice score 0.6% from 0.8714 to 0.8766. The experimental results showed that LAMA improved the segmentation accuracy on both single-lesion and multi-lesion dermoscopic images. The proposed LAMA technique warrants further study.

Diagnostic and therapeutic process of neurofibromatosis type 1 and type 2

Neurofibromatosis is one of the most common genetic diseases. It is inherited in an autosomal dominant manner. It is divided into two genetically distinct subtypes, characterised by multiple skin lesions and tumours of the peripheral and central nervous system. Neurofibromatosis type 1, or Recklinghausen's disease, is the most common phakomatosis. The disease is genetically determined by a mutation of the neurofibromin- 1 gene on chromosome 17. Neurofibromatosis type 2 accounts for 3% of all cases. The disease is genetically determined - caused by a mutation of the neurofibromin-2 gene on chromosome 22. The diagnostic and therapeutic process of neurofibromatosis is a major challenge for clinicians. Given the complexity of the problem, we have reviewed the literature on the diagnostic and therapeutic possibilities of the disease.

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08-7.035), C*03:04 (OR = 3.665, 95%CI: 2.102-6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326-3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions.

Medical management of cutaneous lymphoma and associated ileus in a labrador dog

A 6-year-old male Labrador dog was presented to the Small Animal Medicine unit of the Veterinary Clinical Complex, Veterinary College and Research Institute, Orathanadu with a history of hair loss and multiple skin lumps all over the body. The dog was treated for atopic dermatitis past three weeks. Clinical examination revealed generalized alopecia, lymphadenopathy and nodule-like skin lumps were noticed all over the body. Hemato-biochemical analysis revealed anaemia, lymphocytosis and hypoproteinemia. FNAC of skin lump revealed cutaneous lymphoma. Radiography and ultrasonography examination revealed no evidence of metastasis. The dog was treated with modified Wisconsin Madison protocol. On the 15th week of protocol dog showed a distended abdomen and constipation, further abdominal ultrasonography revealed a distended loop and ileus. Hence the present case was diagnosed as vincristine-associated ileus in a dog. Neostigmine was administered to restore the intestinal motility. The dog showed uneventful recovery from cutaneous lymphoma and as well as vincristine-associated ileus.

Cutaneous metastasis in a case of carcinoma floor of mouth- A rare case report

The incidence of cutaneous metastasis in head and neck cancers is less than 1%. Carcinoma of the oral cavity is one of the most common cancers of the head neck region with frequent metastasis to internal organs, especially the lungs, liver, and bone.We present a case of Carcinoma of floor of mouth with cutaneous metastasis.A 55 year old lady presented to our department with complaints of non-healing ulcer in the oral cavity and ulcerated nodules over neck and chest. On examination, mouth opening tongue mobility was restricted with grade 2 trismus. An ulcer in left gb sulcus, bilateral lymphadenopathy and multiple ulcerated skin nodules on neck and chest wall were noted. CECT Face and Neck showed heterogenously ehancing mass at the floor of mouth involving left buccal mucosa and erosion of mandible, lymph node mets and skin nodules. ECOGPS was 1.She was treated with palliative systemic chemotherapy and thereafter Palliative radiation. Now she is having stable disease and is on metronomic chemotherapy with regular follow up.Our case has highlighted that cutaneous metastasis can be seen in the cancers of floor of mouth. Palliative chemotherapy and radiotherapy can significantly increase Progression free survival and hence the Quality of life of patients with such presentation.

Efficacy and tolerability of a novel cosmetic growth factor serum when used as part of biweekly diamond tip hydradermabrasion treatments on facial skin.

Growth factor preparations have demonstrated effectiveness in reversing age-related changes in facial skin. TNS® Advanced+ Serum (TNS A+ Serum; SkinMedica®, Allergan Aesthetics, an AbbVie Company) and TNS Advanced+ Pro-Infusion Serum for DiamondGlow® (DG-TNS A+; Allergan Aesthetics) combine growth factor technology with active botanical ingredients to target signs of skin aging. This prospective clinical study evaluated the effectiveness and tolerability of biweekly facial hydradermabrasion (DiamondGlow [DG]; Allergan Aesthetics) plus DG-TNS A+ combined with at-home topical TNS A+ Serum. Females aged 25-65 years with mild to severe facial photodamage received 6 biweekly DG plus DG-TNS A+ in-office treatments with at-home twice-daily TNS A+ Serum for 12 weeks. Investigator-assessed clinical grading of multiple skin attributes, subject self-assessments, instrumentation measurements, and clinical grading of irritation parameters (0-3, none to severe) were conducted at Visit 1, Day 3, and biweekly from Weeks 2-12. Twenty-nine women (Fitzpatrick skin types II-VI; 52% White, 41% African American) were enrolled. Immediate significant improvements after 1 DG plus DG-TNS A+ treatment were observed for fine lines/wrinkles, skin smoothness (visual and tactile), radiance, and hydration (all p ≤ 0.004). From Weeks 6-12, all investigator-assessed parameters showed significant improvements versus baseline (all p ≤ 0.002 at Week 12). Mean tolerability scores were <1 across parameters. All subjects (100%) were satisfied with results at Weeks 2-12. The combination of biweekly hydradermabrasion plus DG-TNS A+ with at-home TNS A+ Serum treatments was well tolerated and produced immediate, progressive improvement in multiple signs of photoaging in facial skin.

Isolated Severing of the Long Flexor of the Thumb Following an Electrical Shock: A Case Report

We report a case of isolated severing of the FPL tendon following an electrical shock, A 24 -year-old male suffered from an electrical shock while work on home electrical circuit. The lesion was limited to the right hand, clinical exam showed a deficit of thumb flexion with multiple skin burn lesions, surgical exploration and repair we done after stabilization of the patient.

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment

BackgroundThe outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact.Case presentationA 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours—conforming to the criteria of the Korean Disease Control and Prevention Agency—the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered.ConclusionThis case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Age of Flexible Electronics: Emerging Trends in Soft Multifunctional Sensors.

With the commercialization of first-generation flexible mobiles and displays in the late 2010s, humanity has stepped into the age of flexible electronics. Inevitably, soft multifunctional sensors, as essential components of next-generation flexible electronics, have attracted tremendous research interest like never before. This review is dedicated to offering an overview of the latest emerging trends in soft multifunctional sensors and their accordant future research and development (R&D) directions for the coming decade. First, key characteristics and the predominant target stimuli for soft multifunctional sensors are highlighted. Second, important selection criteria for soft multifunctional sensors are introduced. Next, emerging materials/structures and trends for soft multifunctional sensors are identified. Specifically, the future R&D directions of these sensors are envisaged based on their emerging trends, namely i) decoupling of multiple stimuli, ii) data processing, iii) skin conformability, and iv) energy sources. Finally, the challenges and potential opportunities for these sensors in future are discussed, offering new insights into prospects in the fast-emerging technology.

528 - Rapid skin clearance and itch improvement with upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: results from a phase 3b head-to-head clinical trial (Heads Up)

Abstract Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] ≥16; body surface area ≥10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) ≥3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] ≥4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods Skin clearance was assessed by EASI, with response defined as an improvement ≥75% (EASI75), ≥90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (≥4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a post-hoc analysis. Results EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P&amp;lt;0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P&amp;lt;0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P&amp;lt;0.001), with greater improvement observed as early as week 1 (nominal P&amp;lt;0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P&amp;lt;0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P&amp;lt;0.001), with greater proportions observed as early as week 1 (nominal P&amp;lt;0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P&amp;lt;0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P&amp;lt;0.001) and at week 1 (nominal P&amp;lt;0.001). Conclusions Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement.

IMDDHH: A Contribution to the Understanding of the Disease

Inborn Errors of Immunity (IEI) is an extremely rare group of heterogenous disorders which are characterized by predisposition to severe unusual and recurrent infections, severe allergies, features suggestive of autoimmune conditions and sometimes malignancies. We report a two-year-old female child presented to our emergency department with complaints of a history of recurrent respiratory infections, recurrent skin infections and a recent history of purulent discharge from both ears. Clinical examination revealed acute otitis media, pneumonia, multiple healed skin lesions associated with soft non-tender hepatomegaly and normal cardiac findings. Elevated hepatic transaminases and hypogammaglobulinemia suggested the possibility of an inborn error of immunity. A whole exome sequencing study performed on the patient established a diagnosis of IMDDHH (Immunodeficiency, Developmental Delay, and Hypohomosyteinemia) by revealing a missense mutation in the NFE2L2 gene of chromosome 2q31. Diagnosing such conditions with inborn errors of immunity requires a high index of suspicion combined with a comprehensive knowledge of the structure and function of both innate and adaptive immune systems. Recurrent skin and respiratory infections in a growing child belonging to a low-and-middle-income country like India is a common clinical scenario encountered frequently in pediatric clinic practice and is often ignored after attributing it to poor hygienic conditions. However, with careful history taking and examination, a sub-group of such patients may be isolated with a high probability of an underlying IEI, which can later be confirmed by genetic work-up.

Clinically amyopathic dermatomyositis associated with cutaneous ulcerations: a case-based review

Introduction and importance: Dermatomyositis (DM) is an autoimmune myopathy primarily affecting both muscles and skin. When muscle weakness is not clinically apparent, but characteristic skin lesions are present, the condition is referred to as clinically amyopathic dermatomyositis (CADM). Case presentation: The authors present the case of a 52-year-old female with a typical DM rash, interstitial pneumonia, and multiple skin ulcers. The skin biopsy was consistent with DM, and there were no signs of muscle involvement. Myositis-related and myositis-specific autoantibodies were also negative. Significant improvement was not observed until the patient received successive monthly pulses of methylprednisolone and the introduction of methotrexate. This treatment regimen allowed for the complete tapering of prednisone and resulted in sustained disease control. Clinical discussion: In addition to the case presentation, a narrative literature review was conducted using the MEDLINE database, and an evidence-based treatment flowchart is proposed. CADM is a subtype of DM, related to higher incidences of interstitial lung disease, skin vasculopathy and malignancy. When ulcers or interstitial pneumonia are present, treatment should be early and aggressive. Active screening for neoplasms is recommended, particularly within the first 5 years. Conclusion: The authors presented a case of seronegative CADM featuring skin vasculopathy, successfully treated with consecutive methylprednisolone pulses. Our literature review emphasized the importance of focused CADM management trials, highlighting the need for further research.