The use of chitosan as a skin-regeneration agent in burns injuries: A review

Chitosan is an amino-polysaccharide, traditionally obtained by the partial deacetylation of chitin from exoskeletons of crustaceans. Properties such as biocompatibility, hemostasis, and the ability to absorb physiological fluids are attributed to this biopolymer. Chitosan’s biological properties are regulated by its origin, polymerization degree, and molecular weight. In addition, it possesses antibacterial and antifungal activities. It also has been used to prepare films, hydrogels, coatings, nanofibers, and absorbent sponges, all utilized for the healing of skin wounds. In in vivo studies with second-degree burns, healing has been achieved in at least 80% of the cases between the ninth and twelfth day of treatment with chitosan coatings. The crucial steps in the treatment of severe burns are the early excision of damaged tissue and adequate coverage to minimize the risk of infection. So far, partial-thickness autografting is considered the gold standard for the treatment of full-thickness burns. However, the limitations of donor sites have led to the development of skin substitutes. Therefore, the need for an appropriate dermal equivalent that functions as a regeneration template for the growth and deposition of new skin tissue has been recognized. This review describes the properties of chitosan that validate its potential in the treatment of skin burns.

Cosmeceutical aptitudes of niacinamide: A review

Background: The prevalence and scope of dermatological illness differ from region to region. Based upon type and severity, the conditions may vary from superficial to deep systemic skin infections. Niacinamide, an amide analog of vitamin B3 which was conventionally utilized as a food supplement, is now explored for the management of skin disorders. Being a powerhouse on its own, it is not stored inside the body naturally and has to be acquired from external sources. Areas covered: This review is an attempt to disclose the physiology, pharmacology, and highlight the dermatological potentials of niacinamide, discussing its pharmacological mechanisms, varied commercially available treatments, and novel approaches, i.e., in research and patented formulations. Results: Niacinamide has been verified in treating almost every skin disorder, viz. aging, hyperpigmentation, acne, psoriasis, pruritus, dermatitis, fungal infections, epidermal melasma, non-melanoma skin cancer, etc. It has been reported to possess numerous properties, for instance, anti-inflammatory, antimicrobial, antioxidant, antipruritic, and anticancer, which makes it an ideal ingredient for varied dermal therapies. Long term use of niacinamide, regardless of the skin type, paves the way for new skin cells, makingskin healthier, brighter, and hydrated. Conclusion: Niacinamide possesses a variety of positive characteristics in the field of dermatology. Novel approaches are warranted over current treatments which could bypass the above shortcomings and form an effective and stable system. Hence, niacinamide has the potential to become an individual and a productive component with wide future scope.

Response to Extracorporeal Photopheresis in Patients with Cutaneous T-Cell Lymphoma: A Retrospective Medical Chart Review

INTRODUCTION Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used in the treatment of cutaneous T-cell lymphoma (CTCL) for over 30 years. Clinical trials of newer agents for the treatment of CTCL have shown response rates of approximately 30% in heterogeneous patient populations. The objective of this study was to assess the effectiveness of ECP in the treatment of CTCL patients in real-world clinical practice. METHODS This is an interim analysis of a retrospective medical chart review study conducted at clinical sites in the United States, in which treating physicians were responsible for patient selection and data collection via structured case report forms. Patients with a confirmed diagnosis of CTCL who initiated ECP between January 1, 2017 and February 28, 2019 were included in the study. In addition, patients must have initiated ECP at age ≥18 years with no ECP treatment received within the year prior to data collection, have received at least 3 months of ECP treatment, and have response data available in the patient chart. Data collected included patient demographics, clinical characteristics, and treatments received prior to and concomitantly with ECP. Clinical outcomes were collected every 3 months during treatment for up to 18 months, and included the body surface area (BSA) affected, appearance of new skin lesions, and the physician-rated Clinical Global Impression-Improvement (CGI-I) scores. Response to ECP was defined as >50% reduction in BSA affected at any point during the follow-up period, consisting of the time from ECP initiation through the time of data collection. Data analysis was descriptive in nature. RESULTS Four clinical sites participated in the study and enrolled a total of 26 patients for the interim analysis. Patients were predominantly female (53.8%) and White (88.5%). Mean age at CTCL diagnosis was 68.4 years, and the majority patients were diagnosed with Sézary syndrome (57.5%) or mycosis fungoides (30.8%). Nearly half of patients (46.1%) had stage IV disease at diagnosis (IVA, 26.9%; IVB, 19.2%) and half of patients (50.0%) had lymph node involvement at diagnosis. Median BSA involvement with plaques/patches at diagnosis was 80% (interquartile range [IQR], 20% to 90%). Six patients (23.1%) achieved >50% reduction in BSA affected, and among those, median time to response was 6.0 months (IQR, 2.9 to 15.0 months). New skin lesions appeared in 5 patients (19.2%). Among those with available data, the percentage of patients rated as minimally improved, much improved, or very much improved on the CGI-I was 57.7% at 3 months (N=26), 50.0% at 6 months (N=18), and 60.0% at 9 months (N=15) after ECP initiation. CONCLUSIONS This retrospective observational study describes patient characteristics and clinical outcomes among CTCL-diagnosed patients initiating therapy with ECP. Despite the population treated with ECP in real-world practice being older and having more advanced-stage disease compared to recent clinical trials, response rate was comparable. Disclosures Girardi: Transimmune: Patents & Royalties: Inventor/IP; Helsinn: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; Soligenix: Research Funding; Mallinckrodt Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Stradefy Biosciences Inc: Patents & Royalties: Inventor/IP; Actelion: Membership on an entity's Board of Directors or advisory committees, Research Funding. Huang: Mallinckrodt Pharmaceuticals: Current Employment. Corman: Mallinckrodt Pharmaceuticals: Consultancy. Edmundson: Mallinckrodt Pharmaceuticals: Consultancy. Kale: Mallinckrodt Pharmaceuticals: Consultancy. Rusibamayila: Mallinckrodt Pharmaceuticals: Consultancy. Foss: Kura: Honoraria; Daiichi Sankyo: Honoraria; Seattle Genetics: Honoraria, Speakers Bureau; Acrotech: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Kyowa: Honoraria.

Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery—Starting Points and Recent Developments

During the last decades, several technologies were developed for testing drug delivery through the dermal barrier. Investigation of drug penetration across the skin can be important in topical pharmaceutical formulations and also in cosmeto-science. The state-of- the-art in the field of skin diffusion measurements, different devices, and diffusion platforms used, are summarized in the introductory part of this review. Then the methodologies applied at Pázmány Péter Catholic University are shown in detail. The main testing platforms (Franz diffusion cells, skin-on-a-chip devices) and the major scientific projects (P-glycoprotein interaction in the skin; new skin equivalents for diffusion purposes) are also presented in one section. The main achievements of our research are briefly summarized: (1) new skin-on-a-chip microfluidic devices were validated as tools for drug penetration studies for the skin; (2) P-glycoprotein transport has an absorptive orientation in the skin; (3) skin samples cannot be used for transporter interaction studies after freezing and thawing; (4) penetration of hydrophilic model drugs is lower in aged than in young skin; (5) mechanical sensitization is needed for excised rodent and pig skins for drug absorption measurements. Our validated skin-on-a-chip platform is available for other research groups to use for testing and for utilizing it for different purposes.

Metastatic plasma cell leukemia to the skin: a case report with review of the literature

Plasma cell leukemia (PCL) is a rare variant of leukemia with an aggressive clinical course and a poor prognosis. The cutaneous involvement in PCL is very rare either at clinical presentation of leukemia, namely “leukemia cutis”, or in the metastatic PCL to the skin. We present a case of eruptive multiple cutaneous nodules in a 56-year-old man with metastatic PCL. Histologically, a diffuse dermal and subcutaneous infiltration of ovoid cells with amphophilic cytoplasm and eccentrically located nucleus consistent with plasmacytoid morphology was observed. Neoplastic cells showed strong immunoexpression for CD138 and CD38 consistent with plasma cells phenotype, and loss of expression of CD56. Kappa light chain restriction similar to the phenotype of his PCL was demonstrated. We suggest that the evaluation of new skin lesions in leukemic patients should include a histopathologic examination to establish the diagnosis as soon as possible and a correct management of the disease.

Cutaneous metastatic osteosarcoma – A rare case report

Introduction/Objective Osteosarcoma is an aggressive malignant primary bone tumor with common metastases to lungs via hematogenous spread. Other common sites of metastasis include bone and kidneys. Metastasis (excluding extraskeletal) to the skin is extremely rare. To date, roughly 12 cases of cutaneous metastasis have been reported in the literature. Methods/Case Report We report a 44-year-old female patient with a history of osteosarcoma of proximal tibia who underwent wide local excision in 2018 and subsequent chemotherapy. Approximately 2 years after her initial diagnosis, she presented with a painful mass in the left mid-thigh. Imaging studies revealed a 1.7 cm calcified nodule suspicious for metastatic osteosarcoma or a partially calcified granuloma. Fat necrosis and old hematoma were also considered in the radiographic differential, although less likely. An excisional biopsy was performed, which showed a high grade osteoid-producing tumor involving the deep dermis and subcutaneous adipose tissue confirming a metastasis of osteosarcoma. A new skin nodule developed at the same site six months later; though radiographic imaging studies were suggestive of subcutaneous fat stranding in the setting of cellulitis or vascular insufficiency. Given her prior history, another excisional biopsy was performed, which showed recurrent metastatic osteosarcoma. Results (if a Case Study enter NA) NA Conclusion Metastatic osteosarcoma to the skin is a rarely reported event in the literature. The prior clinical history and high index of clinical suspicion are essential in rendering the correct diagnosis. As the skin may be the first site of metastases it is important to include metastatic osteosarcoma in the differential in patients with a prior history of osteosarcoma who develops new skin or subcutaneous lesions. This case highlights the importance of providing history to the pathologist, as other tumors and non-neoplastic lesions can mimic osteosarcoma, particularly in small biopsy specimens. The easier access to the skin/ subcutis could also aid in obtaining tissue for molecular testing.

Contrast-Enhanced Mammography in the Diagnosis of Breast Angiosarcoma

A 60-year-old female presented for further assessment of a new right breast lump (November 2020). She had a history of a stage I (T1bN0M0) right breast invasive mammary carcinoma, grade 2 (score 7/9) with receptors ER/PR-negative, HER2/neu-positive, diagnosed four years prior to her current presentation. At that time, she was treated with a right breast lumpectomy and local radiation. Breast assessment with contrast-enhanced mammography showed new skin thickening with associated enhancement within the palpable region. Histology of subsequent ultrasound-guided biopsy found radiation-induced breast angiosarcoma. Breast angiosarcoma is a rare entity that represents less than 1% of all breast cancers. To our knowledge, this is the first case describing the imaging findings of breast angiosarcoma on contrast-enhanced mammography.

Development of a Multi-Layer Skin Substitute Using Human Hair Keratinic Extract-Based Hybrid 3D Printing

Large-sized or deep skin wounds require skin substitutes for proper healing without scar formation. Therefore, multi-layered skin substitutes that mimic the genuine skin anatomy of multiple layers have attracted attention as suitable skin substitutes. In this study, a novel skin substitute was developed by combining the multi-layer skin tissue reconstruction method with the combination of a human-derived keratinic extract-loaded nano- and micro-fiber using electrospinning and a support structure using 3D printing. A polycaprolactone PCL/keratin electrospun scaffold showed better cell adhesion and proliferation than the keratin-free PCL scaffold, and keratinocytes and fibroblasts showed better survival, adhesion, and proliferation in the PCL/keratin electrospun nanofiber scaffold and microfiber scaffold, respectively. In a co-culture of keratinocytes and fibroblasts using a multi-layered scaffold, the two cells formed the epidermis and dermal layer on the PCL/keratin scaffold without territorial invasion. In the animal study, the PCL/keratin scaffold caused a faster regeneration of new skin without scar formation compared to the PCL scaffold. Our study showed that PCL/keratin scaffolds co-cultured with keratinocytes and fibroblasts promoted the regeneration of the epidermal and dermal layers in deep skin defects. Such finding suggests a new possibility for artificial skin production using multiple cells.