Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The first-line treatment of the localized form of cutaneous squamous cell carcinoma (cSCC) remains surgical excision. Either conventional excision (CE) with margins or Mohs micrographic surgery (MMS) may be preferred, depending on the risk factors of cSCC, the characteristics of the tumor, and the available technical facilities. METHODS: This article presents a systematic review of the current literature spanning from 1974 to 2023, comparing outcomes of cSCC treated with MMS versus cSCC treated with conventional excision. RESULTS: Out of the 6821 records identified through the database search, a total of 156 studies were screened, of which 10 were included in the review. The majority of the included studies showed that treatment of cSCC with MMS consistently exhibits a significantly lower risk of recurrence compared to treatment with CE. In addition, MMS is emerging as the preferred technique for the resection of cSCC located in aesthetically or functionally challenging anatomical areas. CONCLUSION: The studies generally demonstrate that MMS is a safer and more effective treatment of cSCC than CE. Nevertheless, outcomes such as recurrence rates and cost-effectiveness should be assessed more precisely, in order to allow for a more tailored approach in determining the appropriate indication for the use of MMS.

Dermatological emergencies and determinants of hospitalization in Switzerland: A retrospective study.

BACKGROUND: Dermatologic conditions are estimated to account worldwide for approximately 8% of all visits at emergency departments (EDs). Although rarely life-threatening, several dermatologic emergencies may have a high morbidity. Little is known about ED consultations of patients with dermatological emergencies and their subsequent hospital disposal. OBJECTIVE: We explore determinants and clinical variables affecting patients' disposal and hospitalization of people attending the ED at a Swiss University Hospital, over a 56-month observational period, for a dermatological problem. METHODS: De-identified patients' information was extracted from the hospital electronic medical record system. Generalized estimating equations were used to explore determinants of patient's disposition. RESULTS: Out of 5096 consecutive patients with a dermatological main problem evaluated at the ED, 79% of patients were hospitalized after initial assessment. In multivariable analyses, factors which were significantly associated with an increased admission rate included length of ED stay, age ≥ 45 years, male sex, distinct vital signs, high body mass index, low oxygen saturation, admission time in the ED and number and type of dermatological diagnoses. Only 2.2% of the hospitalized patients were admitted to a dermatology ward, despite the fact that they had dermatological diagnoses critically determining the diagnostic related group (DRG) payment. The number of patients managed by dermatologists during in-patient treatment significantly decreased over the study period. CONCLUSIONS: Our study identifies a number of independent predictors affecting the risk of hospital admission for patients with dermatological conditions, which may be useful to improve patients' disposal in EDs. The results indicate that the dermatological specialty is becoming increasingly marginalized in the management of patients in the Swiss hospital setting. This trend may have significant implications for the delivery of adequate medical care, outcomes and cost-effectiveness. Dermatologists should be more engaged to better position their specialty and to effectively collaborate with nondermatologists to enhance patient care.

Safety of Antiandrogens for the Treatment of Female Androgenetic Alopecia with Respect to Gynecologic Malignancies.

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

Successful Removal of 17 Tattoos Self-Administered Using Black Eyeliner Ink with Quality-Switched Neodymium-Doped Yttrium Aluminum Garnet 1,064-nm Laser: A Case Report.

Introduction: Tattooing has a rich historical presence in various human civilizations, with the earliest physical evidence dating back to around 3258 BC. While acceptance of tattoos is increasing in the Western world, negative associations remain. Short-pulsed lasers, such as Q-Switched (QS) or picosecond lasers, are the gold standard for tattoo removal. Case Presentation: This case report discusses the successful removal of 17 amateur tattoos, which were self-administered by a 19-year-old female patient using black eyeliner ink and sewing needles. The tattoos, distributed across her body, including the face and hands, were partially or completely removed over 10 sessions using the QS Neodymium-doped Yttrium Aluminum Garnet 1,064-nm laser. Conclusion: The factors that influence the efficacy of tattoo removal are highlighted, including tattoo type, location, and coexisting fibrosis. The psychological and social importance of effective tattoo removal is emphasized, particularly for young people seeking to disassociate from past experiences or affiliations.

Chaotic dynamics in X-ray free-electron lasers with an optical undulator.

In this work, the chaotic motions of relativistic electrons in X-ray free-electron lasers are investigated using an optical undulator in the presence of a magnetized ion-channel background. To miniaturize X-ray light sources, the optical undulator is a promising concept. The optical undulator provides higher optical gain than conventional magnetostatic undulators due to its micrometer wavelength. In addition, it reduces the required electron beam energy from several GeV to the multi-MeV range to produce X-ray pulses. The interaction of an optical undulator with an intense relativistic electron beam is a highly non-linear phenomenon that can lead to chaotic dynamics. At synchrotron radiation sources, the possibility of chaos control for X-ray FELs can be critical for certain classes of experimental studies. The equations of motion for a relativistic electron propagating through the optical undulator in the presence of a magnetized ion-channel can be derived from the Hamiltonian of the interaction region. Simulation results revealed that the intensity of the perturbation route from orderly behavior to chaos depends on the beam density, axial magnetic field strength, ion-channel density parameter, and pump laser undulator. Specific values of parameters were obtained for the transition from regular to chaotic paths. Bifurcation diagrams of the system were plotted to demonstrate the origin of chaos at a critical point, and Poincaré maps were created to distinguish between chaotic and orderly motions of electrons. The proposed new scheme can help to improve X-ray FELs, which have potential usages in basic sciences, medicine, and industry.

Case report: Area of focus of management of severe pityriasis rubra pilaris by dose optimization of adalimumab biosimilar in combination with acitretin and montelukast.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies.

Effects of cold atmospheric-pressure plasma in combination with doxorubicin drug against breast cancer cells in vitro and invivo.

Cold atmospheric plasma (CAP) has been suggested for medical applications that can be applied indirectly through plasma-activated medium (PAM) and recently it has been introduced as an innovative therapeutic approach for all cancer types. Studies have exhibited that ROS/RNS are key factors in CAP-dependent apoptosis; nevertheless, ROS/RNS stability are weak. Combination therapy is considered an effective strategy to overcome these problems. In the present research, we revealed that the combination of CAP and doxorubicin (DOX) significantly induces the apoptosis of breast cancer cells both in vitro and in vivo. Our results indicated that both Ar and He/O2 CAP treatment as well as DOX drug alone reduced cell growth. CAP/PAM treatment in combination with DOX induced apoptosis in MCF-7 breast cancer cells and 4T1-implanted BALB/c mice, resulting in a significant increase in antitumor activity. The apoptotic effects of CAP-DOX on MCF-7 cells were inferred from altered expression of BAX and cleaved-caspase-3 which mechanistically take place through the mitochondrial pathway mediated by Bcl-2 family members. Besides, the BAX/BCL-2 ratio is significantly higher in the simultaneous treatment of CAP and DOX. This ratio was equal to 2.82 ± 0.24, 2.54 ± 0.30, and 11.27 ± 0.31 for treatment with DOX, He/O2 plasma, and combination treatment, respectively. Additionally, the tumor growth rate of He/O2-PAM + DOX and Ar-PAM + DOX treatments was significantly inhibited by PAM-injection, and the tumor growth rate of PAM alone or DOX alone was slightly reduced. It can be concluded that the effect of PAM + DOX may increase the anticancer activity and decrease the dose required for the chemotherapeutic treatment.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

HPV Vaccination in Immunosuppressed Patients with Established Skin Warts and Non-Melanoma Skin Cancer: A Single-Institutional Cohort Study.

cSCC (cutaneous squamous cell carcinoma) and its precursors are a major cause of morbidity, especially in immunosuppressed patients, and are frequently associated with human papillomavirus (HPV) infections. The purpose of this study is to investigate the therapeutic potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. In this retrospective study, all patients who received Gardasil-9®, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated Poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p < 0.001) between pre- and post-Gardasil-9® intervention. Gardasil-9® vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 caseloads during the observational period. Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions and overall mortality as well as healthcare costs in immunosuppressed patients with high skin tumor burden.

Antimicrobial activity of cold atmospheric-pressure argon plasma combined with chicory (Cichorium intybus L.) extract against P. aeruginosa and E. coli biofilms.

The present study reports a significant combined antibacterial activity of Cichorium intybus L. (known as Chicory) natural extract with cold atmospheric-pressure argon plasma treatment against multi-drug resistant (MDR) Gram-negative bacteria. To detect reactive species that are generated in the argon plasma, optical emission spectra were recorded. The molecular bands were allocated to the hydroxyl radicals (OH) and neutral nitrogen molecules (N2). Moreover, the atomic lines form the emitted spectra were determined to argon atoms (Ar) and the oxygen atoms (O), respectively. The results revealed that Chicory extract treatment at a concentration of 0.043 g/ml reduced the metabolic activity of P. aeruginosa cells by 42%, while, a reduced metabolic activity of 50.6% was found for E. coli biofilms. Moreover, the combination of Chicory extract with 3 min Ar-plasma introduced a synergistic effect, so that it exhibited a significantly reduced metabolic activity of P. aeruginosa to 84.1%, and E. coli ones to 86.7%, respectively. The relationship between cell viability and membrane integrity of P. aeruginosa and E. coli biofilms treated with Chicory extract and argon plasma jet were also analyzed by CLSM. It was found that after the combined treatment, a noticeable membrane disruption was formed. Besides, it was concluded that E. coli biofilms showed a higher sensitivity to Ar-plasma than P. aeruginosa biofilm at longer plasma exposure times. This study suggests that the anti-biofilm therapy based on a combined effect of Chicory extract and cold argon plasma treatment can serve as a considerable green method for treatment of antimicrobial MDR bacteria.

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems.

BACKGROUND: Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS: To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS: Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS: Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION: Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.

Randomized Open-Label Trial Comparing Teledermatology vs. Face-to-Face Consultation in the Follow-Up of Patients with Mild-to-Moderate Acne.

Background: Acne vulgaris is one of the most common dermatological diseases, especially in adolescents and young adults. Objective: The current study aimed to compare teledermatology versus face-to-face consultation in the follow-up of patients with mild-to-moderate acne. Methods: In this investigator-initiated, parallel arms, open-label, randomized clinical trial, after screening, participants were randomly assigned in a 1:1 ratio to be followed up through teledermatology or standard face-to-face consultations for a period of 6 months. The primary endpoint was the cumulative time spent by physician for consultations or online assessments. Results: Out of 24 patients (21 females and 3 males; mean age 23.0 ± 3.3 years) underwent randomization in the two study groups. In intention-to-treat analysis, the cumulative time spent by physician was higher in the teledermatology group compared to face-to-face consultations with an average difference of 8:24 mm:ss (95% CI: 1:17-15:31). However, the cumulative time spent by the patient was significantly lower in the teledermatology group (mean difference 1:21:39 hh:mm:ss; 95% CI: 41:51-2:01:27). An optimal reduction of acne-severity was observed in both groups, without significant differences between them. The patient's satisfaction did not change significantly over time and between groups, and was generally quite high. AEs were reported by one patient in the teledermatology group and four patients in the consultation group. Conclusion: Acne might be an optimal disease to be followed up using a teledermatology platform, to relieve the burden on patients and medical staff. However, it is necessary to implement more user-friendly platforms in order to achieve the best possible results in the treatment and follow-up of acne patients.

Canakinumab leads to rapid reduction of neutrophilic inflammation and long-lasting response in Schnitzler syndrome.

Interleukin-1 (IL-1)-blocking therapies are effective in reducing disease severity and inflammation in Schnitzler syndrome. Here, we present a patient with Schnitzler syndrome treated successfully using canakinumab for over 10 years. Complete clinical response was associated with a decrease in dermal neutrophil number and expression of the pro-inflammatory cytokines IL-1ß, IL-8, and IL-17 as assessed by immunohistochemical studies.

Long-Term Follow-Up of Lentigo Maligna Patients Treated with Imiquimod 5% Cream.

BACKGROUND: The study investigated the long-term efficacy of imiquimod 5% cream for LM, with a focus on disease recurrence and the possible prognostic factors of disease-free survival (DFS) in a cohort, with long-term follow-up. METHODS: Consecutive patients with histologically confirmed LM were included. Imiquimod 5% cream was applied until weeping erosion appeared on the LM-affected skin. The evaluation was performed through clinical examination and dermoscopy. RESULTS: We analyzed 111 patients with LM (median age: 72 years, 61.3% women) with tumor clearance after imiquimod therapy, with a median follow-up of 8 years. The overall patient survival rates were 85.5% (95% confidence interval (CI): 78.5-92.6) and 70.4% (95% CI: 60.3-80.5) at 5 and 10 years, respectively. Among the 23 patients (20.1%) with relapse at follow-up, 17 (73.9%) were treated with surgery, five (21.7%) continued imiquimod therapy, and one (4.3%) underwent both surgery and radiotherapy. After adjustment for age and LM area in multivariable models, localization of LM in the nasal region was identified as a prognostic factor for DFS (HR = 2.66; 95% CI: 1.06-6.64). CONCLUSION: If surgical excision is not possible due to the patients' age/comorbidities or critical cosmetic localization, imiquimod could provide optimal outcomes with an optimal risk of relapse for the management of LM.

Superparamagnetic MnFe alloy composite derived from cross-bindered of chitosan/rice husk waste/iron aluminate spinel hercynite for rapid catalytic detoxification of aflatoxin B1: Structure, performance and synergistic mechanism.

The contamination of foodstuffs with aflatoxins B1 (AFB1) as carcinogen/mutagens toxin produced by Aspergillus fungi that are a major threat to the economy, safe food supply, and human health. To, we present a facile wet-impregnation and co-participation strategies for the construction of a novel superparamagnetic MnFe biocomposite (MF@CRHHT), in which dual metal oxides MnFe were anchored in/on agricultural/forestry residues (chitosan/rice husk waste/hercynite hybrid nanoparticles) and applied for rapid AFB1 detoxification by destroying in a non-thermal/microbial way. Structure, and morphology were comprehensively characterized by various spectroscopic analyses. The AFB1 removal in PMS/MF@CRHHT system followed pseudo-first-order kinetics, and exhibited excellent efficiency (99.3 % in 20 min and 83.1 % in 5.0 min) over a broad pH range (5.0-10.0). Importantly, relationship between high efficiency and physical-chemical properties, and mechanistic insight reveals that the synergistic effect could be related to the formation MnFe bond in MF@CRHHT and then mutual electron transfer between them to enhanced electron density and generate reactive oxygen species. An AFB1 decontamination pathway proposed was based on the free radical quenching experiments and analysis of the degradation intermediates. Thus, the MF@CRHHT can be applied as an efficient, cost-effective, recoverable, environment-friendly and highly efficient biomass-based activator for remediate pollution.

Macroalgae as biofactories of metal nanoparticles; biosynthesis and food applications.

Nanotechnology has opened a new frontier in recent years, capable of providing new ways of controlling and structuring products with greater market value and offering significant opportunities for the development of innovative applications in food processing, preservation, and packaging. Macroalgae (MAG) are the major photoautotrophic group of living beings known as a potential source of secondary metabolites, namely phenolic compounds, pigments, and polysaccharides. Biosynthesis based on the abilities of MAG as "nanobiofactories" targets the use of algal secondary metabolites as reducing agents to stabilize nanoparticles (NPs). Nowadays, most of the studies are focused on the use of metal (Ag, Au) and metal-oxide (CuO, ZnO) NPs derived from algae. The eco-friendly biosynthesis of metal NPs reduces the cost and production time and increases their biocompatibility, due to the presence of bioactive compounds in MAG, making them suitable for a wide variety of applications. These compounds have been attributed to the antimicrobial and antioxidant properties responsible for their application through innovative technologies such as nanoencapsulation, nanocomposites, or biosensors in the food industry. Nevertheless, toxicity is a key factor that should be considered, so the applicable regulation needs to guarantee the safe use of metal NPs. Consequently, the aim of this review will be to compile the available information on MAG-mediated metal NPs, their biosynthesis, and potential food applications.

Skin hyperpigmentation after sclerotherapy with polidocanol: A systematic review.

Skin hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants is a common local side effect. Sclerotherapists should be familiar with factors that trigger hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants. A systematic literature review of works reporting hyperpigmentation after sclerotherapy for telangiectasias, reticular veins, side branches and truncal varices with polidocanol-containing sclerosants was performed. Reported incidence rates, follow-up periods and potentially triggering factors were assessed and analysed. The search yielded 1687 results; of these, 27 reports met the inclusion criteria. The incidence of hyperpigmentation seemed to increase with higher concentrations of polidocanol and was more evident after sclerotherapy for epifascial veins than for intrafascial truncal veins when the polidocanol concentration was more than 0.25%. Regarding sclerotherapy for telangiectasias and reticular veins, the incidence of hyperpigmentation ranged between 2% and 25% for polidocanol 0.25% (liquid and foam), between 12.5% and 67.9% for polidocanol 0.5% (liquid and foam) and between 13% and 73% for polidocanol 1% (liquid and foam). Regarding truncal veins, the incidence ranged from 7% to 45.8% for polidocanol 1% (liquid and foam), from 16% to 17% for polidocanol 2% (foam) and from 7.4% to 32.5% for polidocanol 3% (liquid and foam). Regarding the treatment of side branches, the incidence of hyperpigmentation ranged from 5.6% to 53% for both foam and liquid sclerotherapy. Regarding the duration of hyperpigmentation, there are few data describing reticular veins and telangiectasias. Hyperpigmentation persisting for more than 6 months has been reported to have an incidence of up to 7.5%. Hyperpigmentation persisting for more than 1 year after foam polidocanol 1%-3% treatment for truncal veins has an incidence ranging from 8.1% to 17.5%. Other factors such as higher volumes and compression therapy after treatment seem to have a minor influence. Data regarding hyperpigmentation after polidocanol-related sclerotherapy are poor and should be improved by higher-quality research.

Subcapsular Sinus Macrophages Promote Melanoma Metastasis to the Sentinel Lymph Nodes via an IL1α-STAT3 Axis.

During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLN. We found that macrophages located in the subcapsular sinus (SS) produced protumoral IL1α after recognition of tumoral antigens. Moreover, we confirmed that the elimination of LN macrophages or the administration of an IL1α-specific blocking antibody reduced metastatic spread. To understand the mechanism of action of IL1α in the context of the sLN microenvironment, we applied single-cell RNA sequencing to microdissected metastases obtained from animals treated with the IL1α-specific blocking antibody. Among the different pathways affected, we identified STAT3 as one of the main targets of IL1α signaling in metastatic tumor cells. Moreover, we found that the antitumoral effect of the anti-IL1α was not mediated by lymphocytes because Il1r1 knockout mice did not show significant differences in metastasis growth. Finally, we found a synergistic antimetastatic effect of the combination of IL1α blockade and STAT3 inhibition with stattic, highlighting a new immunotherapy approach to preventing melanoma metastasis.