Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study.

Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. Rhenium skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm2 in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. Results: A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 (n = 19), grade 2 (n = 9), or grade 3 (n = 1). Conclusion: This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy.

Advancing inflammatory skin disease therapy: Sustained tofacitinib release via electrospun fiber dressings.

Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings - uniaxial, coaxial, and layer-by-layer - were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies - a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.

EVALUATION OF ANTICANCER THERAPY- RELATED DERMATOLOGIC ADVERSE EVENTS: INSIGHTS FROM FDA's FAERS DATASET.

BACKGROUND: New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking. METHODS: This study utilized the FDA's Adverse Event Reporting System (FAERS) database (January 2013-September 2022), with 3,399,830 reports involving 3,084 drugs and 16,348 AEs. A nearest neighbor matching model was employed to select 10 controls for each case report, utilizing the cosine similarity of demographic and AE severity factors to minimize false positives/ negatives. RESULTS: There were 10,698 unique anticancer drugs (n=212) to skin AE (n=873) pairs, of which 676 had significant Reporting Odds Ratios (ROR) >1, comprising 113 drugs and 144 AEs. The minimum ROR was 1.25, and 50% of associations displayed a ROR >10. The most common were rash (51 agents) and dry skin (28 drugs). Methotrexate induced the most distinct AEs (34), then mechlorethamine (33), and vemurafenib (24). Targeted therapies accounted for 49% of pairs, cytotoxic chemotherapies for 35.9%, and immunotherapies for 11%. CONCLUSIONS: 113 anticancer drugs were identified as significantly associated with skin AEs, most frequently rash and dry skin. Data are likely underreported but enable quick post-marketing identification of skin toxicity signals.

Investigation of verapamil-induced cardiorenal dysfunction and compensatory ion regulation in zebrafish embryos.

The purpose of the present study was to investigate the development of verapamil-induced cardiorenal failure and the response of epidermal ionocytes in zebrafish embryos to this syndrome. Zebrafish embryos were exposed to verapamil for 24 h at different developmental stages (48, 72, and 96 h post-fertilization). The exposure resulted in the generation of edema in the pericardial and yolk sac regions, with more-pronounced effects observed in later-stage embryos. Cardiac parameters showed a suppressed heart rate at all stages, with a more-significant effect appearing in later stages. Verapamil also affected cardiac parameters including the end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and cardiac output (CO), indicating negative overall effects on cardiac performance. mRNA levels of heart failure markers (nppa and nppb genes) were upregulated in verapamil-exposed embryos at all stages. Renal function was impaired as FITC-dextran excretion was suppressed. A whole-embryo ion content analysis revealed significant increases in sodium and calcium contents in verapamil-exposed embryos. The density of epidermal ionocytes increased, and the apical membrane of ionocytes was enlarged, indicating upregulation of ion uptake. In addition, mRNA levels of several ion transporter genes (rhcg1, slc9a3, atp6v1a, atp2b1a, trpv6, and slc12a10.2) were significantly upregulated in verapamil-exposed embryos. In summary, prolonged exposure to verapamil can induce cardiorenal failure which triggers compensatory upregulation of ionocytes in zebrafish embryos.

Rate of skin and nerve complications as a result of cutaneous traction with modern foam boots.

INTRODUCTION: Cutaneous traction is used to temporize lower extremity fractures and relies on friction between the skin and surrounding material to apply a longitudinal force. This circumferential compressive force can lead to pressure sores, skin sloughing, or compressive neuropathies. These complications have been reported in up to 11% of patients when the cutaneous traction relies on adhesive tapes, plaster, and rubber bandages being in immediate contact with the skin. The rates of these complications are not well documented when using modern foam boots. METHODS: A retrospective chart review was performed on all orthopedic trauma patients who suffered pelvic or lower extremity injuries between March 1st, 2020 and April 30th, 2021 at a single Level-1 trauma center. We included all patients with femoral fractures, axially unstable pelvic ring and/or acetabular fractures, and unstable hip dislocations temporized with the use of cutaneous traction. All patients had intact skin and lower extremity nerve function prior to application. RESULTS: There were 138 patients identified with 141 lower extremities. The average patient age was 50.7 (6-100) years. Mean traction weight of 9.8 (5-20) pounds. Average traction duration was 20.9 (2.3-243.5) hours. At the time of traction removal, there was 1 (0.7%) new skin wound and 0 nerve palsies. The new skin wound was a stage one heel pressure sore and did not require further treatment. CONCLUSION: Cutaneous traction with a modern foam boot was found to have a skin complication rate of 0.7% and a nerve palsy complication rate of 0% for an overall complication rate of 0.7%, which has not been previously established and is lower than historically reported complication rates of 11% when utilizing adhesive and plaster directly on skin. Foam boot Cutaneous traction may be considered a safe option for traction placement.

Access to systemic treatment of non-melanoma skin cancer in Spain: a survey analysis.

BACKGROUND: Novel and highly effective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain's decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access. METHODS: A cross-sectional survey (July-September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs. FINDINGS: Fifty physicians from 15 Spanish AaCc responded to the survey. Access for drug with approved public reimbursement, Hedgehog inhibitors in basal-cell carcinoma and anti PD-L1 antibody in Merkel carcinoma, was observed in 84% and 86% of centers, respectively. For other EMA-approved treatments, but without reimbursement in Spain access decreased to 78% of centers. Heterogeneity in access was mainly observed intra regions. CONCLUSION: Unequal financial support for drugs for NMSC with creates a patchwork of access across Spanish hospitals, with variations even within the same AaCc.

Topical retinoids: Novel derivatives, nano lipid-based carriers, and combinations to improve chemical instability and skin irritation.

BACKGROUND: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti-aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products. AIM: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges. METHODS: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid-based carriers, liposomes, penetration-enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed. RESULTS: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid-based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family. CONCLUSIONS: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid-based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods.

Rotational radiofrequency-based technology leads to adipose tissue reduction and contouring effect in the thighs, abdomen, and flanks.

BACKGROUND: Excess body adiposity and skin irregularities represent a major problem in today's society. Currently, radiofrequency-based devices constitute an increasingly popular medical-aesthetic application and a powerful non-invasive method to combat this problem. OBJECTIVE: This study aims to determine the efficacy and safety of the high-frequency device Zionic™ (Termosalud, Inc., Gijón, Spain) in reducing body contouring and improving skin appearance in the abdomen/flanks or thighs. MATERIALS AND METHODS: Thirty nine individuals were treated with the Zionic™ device in the abdomen/flanks or thighs. A total of 8 sessions of 40-50 min each, 72/96 h apart were performed. At baseline, body measurements were taken including photographs, body contours, and ultrasound scans to assess dermal thickness, dermal echogenicity, and subcutaneous fat thickness. The measurements were repeated after the eight sessions for comparison and analysis. Quantitative data was complemented with a customized survey to evaluate participants satisfaction level. RESULTS: At the follow-up visit, a significant average reduction of 3% in abdomen/flanks circumferences and 2% in thighs contours was noticed. Abdomen/flanks and thighs subcutaneous fat layer thickness was significantly reduced by 8% and 6%, respectively. Dermal echogenicity changes, related to skin collagen content and organization, showed non-significant increasing tendencies of 7% for abdomen/flanks and 8% for thighs. Thighs dermal thickness was significantly increased by 6%. Results were associated to a high satisfaction level (80%) and no severe adverse events. CONCLUSION: Zionic™ treatment is a safe, effective, and well-tolerated noninvasive procedure for body contouring and improvement of skin properties in abdomen, flanks, and thighs.

The Role of Probiotics in Skin Care: Advances, Challenges, and Future Needs.

The skin, being the largest organ in the human body, plays a pivotal role in safeguarding the body against invasive pathogens. Therefore, it is essential to reinforce and protect this vital organ. Current research supports the impact of probiotics on skin health and their ability to alleviate various skin disorders. However, the effectiveness and probable side effects of probiotics in skin care remain a subject of debate, necessitating further investigation and analysis. Hence, this study aims to highlight existing gaps and future needs in the current research on probiotics in skin care and pave the way for future investigations. Therefore, we scrutinized the effects of oral (fermented foods and dietary supplements) and non-oral/topical probiotics on skin care, and the mechanism of probiotics that affect skin health. The results of most studies showed that fermented foods containing probiotics, particularly dairy products, positively impact skin health. The research results regarding the efficacy of probiotic supplements and live strains in treating skin disorders show promising potential. However, safety evaluations are crucial, to identify any potential adverse effects. While research has identified numerous potential mechanisms by which probiotics may influence skin health, a complete understanding of their precise mode of action remains elusive. However, it seems that probiotics can exert their positive effects through the gut-skin and gut-skin-brain axis on the human body. Therefore, following the identification of safe probiotics, additional studies should be carried out to establish optimal dosages, potential side effects, suitable regulatory guidelines, and validation methods.

Palliative care in dermatooncology - Current practice in German dermatooncological centers and specialist offices.

BACKGROUND: Dermato-oncology patients are often treated in certified skin cancer centers or dermato-oncological specialist offices. Especially in higher tumor stages, patients develop symptoms, either disease-related or due to therapy-related side effects, requiring treatment. Despite a markedly improved prognosis since the introduction of targeted therapies and immunotherapies, advance care planning is required in progressive disease. It is unclear how palliative care of skin cancer patients is currently organized in dermato-oncology. PATIENTS AND METHODS: In a nationwide survey, all certified skin cancer centers and dermato-oncological specialist offices in Germany were contacted and asked to participate in this anonymized survey. RESULTS: Overall, 45 responses (42%) were received. The majority (98%) of the respondents screen the patients on a regular basis for distressing symptoms, and all centers are connected to palliative medical care providers. Only 5% of the medical staff members have the additional qualification "palliative medicine". In 68% of the participating institutions, the opportunity for care planning is offered to patients. For 89%, palliative care is relevant for everyday work, and 82% desire more research opportunities on this topic. CONCLUSIONS: This survey has shown that palliative care plays a major role in dermato-oncological work. Given that only a small proportion of the staff have received specialized training in palliative care, however, an increase of this proportion would be desirable for comprehensive care.

Characterising the Tasmanian devil (Sarcophilus harrisii) pouch microbiome in lactating and non-lactating females.

Wildlife harbour a diverse range of microorganisms that affect their health and development. Marsupials are born immunologically naïve and physiologically underdeveloped, with primary development occurring inside a pouch. Secretion of immunological compounds and antimicrobial peptides in the epithelial lining of the female's pouch, pouch young skin, and through the milk, are thought to boost the neonate's immune system and potentially alter the pouch skin microbiome. Here, using 16S rRNA amplicon sequencing, we characterised the Tasmanian devil pouch skin microbiome from 25 lactating and 30 non-lactating wild females to describe and compare across these reproductive stages. We found that the lactating pouch skin microbiome had significantly lower amplicon sequence variant richness and diversity than non-lactating pouches, however there was no overall dissimilarity in community structure between lactating and non-lactating pouches. The top five phyla were found to be consistent between both reproductive stages, with over 85% of the microbiome being comprised of Firmicutes, Proteobacteria, Fusobacteriota, Actinobacteriota, and Bacteroidota. The most abundant taxa remained consistent across all taxonomic ranks between lactating and non-lactating pouch types. This suggests that any potential immunological compounds or antimicrobial peptide secretions did not significantly influence the main community members. Of the more than 16,000 total identified amplicon sequence variants, 25 were recognised as differentially abundant between lactating and non-lactating pouches. It is proposed that the secretion of antimicrobial peptides in the pouch act to modulate these microbial communities. This study identifies candidate bacterial clades on which to test the activity of Tasmanian devil antimicrobial peptides and their role in pouch young protection, which in turn may lead to future therapeutic development for human diseases.

Assessing Barrier Function in Psoriasis and Cornification Models of Artificial Skin Using Non-Invasive Impedance Spectroscopy.

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers - the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non-invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full-thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVES: Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. METHODS: We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. RESULTS: Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. DISCUSSION: This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Clinical outcomes in people with diabetes-related foot infections: Analysis from a limb preservation service infection database.

BACKGROUND: Diabetes-related foot infections are common and represent a significant clinical challenge. There are scant data about outcomes from large cohorts. The purpose of this study was to report clinical outcomes from a large cohort of people with diabetes-related foot infections. METHODS: A tertiary referral hospital limb preservation service database was established in 2018, and all new episodes of foot infections were captured prospectively using an electronic database (REDCap). People with foot infections between January 2018 and May 2023, for whom complete data were available on infection episodes, were included. Infection outcomes were compared between skin and soft tissue infections (SST-DFI) and osteomyelitis (OM) using chi-square tests. RESULTS: Data extraction identified 647 complete DFI episodes in 397 patients. The data set was divided into two cohorts identifying each infection episode and its severity as either SST-DFI (N = 326, 50%) or OM (N = 321, 50%). Most infection presentations were classified as being moderate (PEDIS 3 = 327, 51%), with 36% mild (PEDIS 2 = 239) and 13% severe (PEDIS 4 = 81). Infection resolution occurred in 69% (n = 449) of episodes with failure in 31% (n = 198). Infection failures were more common with OM than SST-DFI (OM = 140, 71% vs. SST-DFI = 58, 29%, p < 0.00001). In patients with SST-DFI a greater number of infection failures were observed in the presence of peripheral arterial disease (PAD) compared to the patients without PAD (failure occurred in 30% (31/103) of episodes with PAD and 12% (27/223) of episodes without PAD; p < 0.001). In contrast, the number of observed infection failures in OM episodes were similar in patients with and without PAD (failure occurred in 45% (57/128) of episodes with PAD and 55% (83/193) of episodes without PAD; p = 0.78). CONCLUSIONS: This study provides important epidemiological data on the risk of poor outcomes for DFI and factors associated with poor outcomes in an Australian setting. It highlights the association of PAD and treatment failure, reinforcing the need for early intervention to improve PAD in patients with DFI. Future randomised trials should assess the benefits of revascularisation and surgery in people with DFI and particularly those with OM where outcomes are worse.

Long noncoding RNA MALAT1 in dermatologic disorders: a comprehensive review.

Dermatologic disorders, affecting the integumentary system, involve diverse molecular mechanisms such as cell proliferation, apoptosis, inflammation and immune responses. Long noncoding RNAs, particularly Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), are crucial regulators of gene expression. MALAT1 influences inflammatory responses, immune cell function and signaling pathways, impacting various physiological and pathological processes, including dermatologic disorders. Dysregulation of MALAT1 is observed in skin conditions like psoriasis, atopic dermatitis and systemic lupus erythematosus. However, its precise role remains unclear. This review consolidates knowledge on MALAT1's impact on skin biology and pathology, emphasizing its potential diagnostic and therapeutic implications in dermatologic conditions.

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ELA-Net: An Efficient Lightweight Attention Network for Skin Lesion Segmentation.

In clinical conditions limited by equipment, attaining lightweight skin lesion segmentation is pivotal as it facilitates the integration of the model into diverse medical devices, thereby enhancing operational efficiency. However, the lightweight design of the model may face accuracy degradation, especially when dealing with complex images such as skin lesion images with irregular regions, blurred boundaries, and oversized boundaries. To address these challenges, we propose an efficient lightweight attention network (ELANet) for the skin lesion segmentation task. In ELANet, two different attention mechanisms of the bilateral residual module (BRM) can achieve complementary information, which enhances the sensitivity to features in spatial and channel dimensions, respectively, and then multiple BRMs are stacked for efficient feature extraction of the input information. In addition, the network acquires global information and improves segmentation accuracy by putting feature maps of different scales through multi-scale attention fusion (MAF) operations. Finally, we evaluate the performance of ELANet on three publicly available datasets, ISIC2016, ISIC2017, and ISIC2018, and the experimental results show that our algorithm can achieve 89.87%, 81.85%, and 82.87% of the mIoU on the three datasets with a parametric of 0.459 M, which is an excellent balance between accuracy and lightness and is superior to many existing segmentation methods.

Bio-Skin-Inspired Flexible Pressure Sensor Based on Carbonized Cotton Fabric for Human Activity Monitoring.

With the development of technology, people's demand for pressure sensors with high sensitivity and a wide working range is increasing. An effective way to achieve this goal is simulating human skin. Herein, we propose a facile, low-cost, and reproducible method for preparing a skin-like multi-layer flexible pressure sensor (MFPS) device with high sensitivity (5.51 kPa-1 from 0 to 30 kPa) and wide working pressure range (0-200 kPa) by assembling carbonized fabrics and micro-wrinkle-structured Ag@rGO electrodes layer by layer. In addition, the highly imitated skin structure also provides the device with an extremely short response time (60/90 ms) and stable durability (over 3000 cycles). Importantly, we integrated multiple sensor devices into gloves to monitor finger movements and behaviors. In summary, the skin-like MFPS device has significant potential for real-time monitoring of human activities in the field of flexible wearable electronics and human-machine interaction.