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In recent years, severe ocular complications after dermatological laser therapies have been reported. One hypothesis is thermal damage due to heating of the metal eye shields. The aim of the present study is to evaluate the safety of ocular metal eye shields during laser therapy of the periocular region. For the experimental study, porcine eyelids were exposed to continuously increasing laser energy and multiple pulses using a number of dermatologic laser systems. Temperature differences of the convex and concave surface of metal eye shields were constantly measured using a thermocouple. Maximum increase of the convex surface of shields was + 8.9 °C (± 0.1 °C) provided by the long-pulsed alexandrite laser (20–25-J/cm2 energy, 15-mm spot size, 20-ms pulse duration, 1 Hz). Present data indicate that metal eye shields provide sufficient thermal protection when clinically used laser parameters are applied. Other safety precautions continue to be essential to protect both the patient and the laser operator. These include the use of nonreflective metal eye shields, precise knowledge of laser physics, and a clear understanding of how they interact with ocular and periocular anatomy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radiofrequency microneedling (RFMN) treatment is the latest generation of fractional skin rejuvenation methods. OBJECTIVE: To evaluate the efficacy, safety, tolerability and patient satisfaction of RFMN treatment for skin rejuvenation of the lower face and neck area. MATERIALS AND METHODS: A prospective, intraindividual, controlled study. Subjects were treated with a fractional insulated RFMN system with 1 to 3 sessions at intervals of 4 to 12 weeks. Follow-up visits were scheduled on Day 90 and 180 posttreatment. Outcome was assessed by volume analysis of standardized 3-dimensional imaging, and validated clinical scales were rated by the physician, a blinded investigator, and patients. RESULTS: Thirty patients (mean age 55.5 years, Fitzpatrick skin type I–IV) were included. Mean submental volume difference was −4.72 cm3 (±10.07 cm3; range −26.65 cm3 to +16.01 cm3). Physician, blinded investigator, and subjects rated the clinical outcome as highly improved. Mean pain intensity was 5.61/10 on Numeric Rating Scale. Beside slight swelling and redness, no relevant downtime has been observed. CONCLUSION: Fractional RFMN treatment is a safe and effective technique for rejuvenation of the lower face, jawline, and neck region. Sufficient pain management should be provided. Data indicated low to no downtime and high patient satisfaction. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusions Telangiectasia is a prominent feature of rosacea leading to a high demand for effective treatment. To ensure consistent clinical and scientific evaluations and assess treatment response accurately, standardized assessment tools are necessary for grading the severity of telangiectasia. However, no validated grading scales for this condition are currently available.To develop and validate a photonumeric scale for assessing the severity of telangiectasia in rosacea patients.The five‐point photonumeric Telangiectasia in Rosacea Severity Assessment (TRoSA) scale was developed for the severity of telangiectasia in rosacea. Sixteen experts participated in the validation process, evaluating 50 images of rosacea patients in two rounds. Interrater and intrarater reliability were analyzed using the intraclass correlation coefficient (ICC) and weighted kappa, respectively.Interrater reliability was found to be “almost perfect” in both validation rounds (Round 1: ICC 0.847; Round 2: ICC 0.828). The mean weighted kappa indicated “substantial” intrarater reliability between the two rounds with a weighted kappa of 0.719. A bubble plot of the two rounds illustrated a diagonal order, confirming the consistency of the intrarater agreement.The TRoSA scale demonstrated high interrater and intrarater reliability indicating that it is a consistent and reproducible tool for grading the severity of telangiectasia in rosacea. This scale can standardize clinical assessments, assisting in diagnosis, treatment planning, and evaluation of therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background: Adjuvant treatment of stage II–IV melanoma with PD‐1‐based immune checkpoint inhibitors (ICI) has improved relapse‐free survival (RFS) and has therefore become a standard‐of‐care treatment option. Approximately 25%–30% of patients still recur within 1 year. Predictive biomarkers reflecting real‐world data are desired. The predictive relevance of tumour tissue PD‐L1 expression in the adjuvant setting remains inconclusive. Objectives: This retrospective, observational study was conducted to evaluate the value of PD‐L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment. Methods: Tumour tissue taken prior to anti‐PD‐1 adjuvant ICI in 243 stage II–IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD‐L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut‐off (CO) levels (relapse‐free survival, RFS) for different tumour tissue locations (primary tumour, metastases). Results: A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37). Conclusions: PD‐L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell‐type relevant for the predictive value of PD‐L1 expression is tissue‐specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort. [ABSTRACT FROM AUTHOR]

Background: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. Aims: To examine patient‐reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). Methods: Retrospective, cross‐sectional study with data from a German direct‐to‐consumer teledermatology platform between December 2021 and January 2023. Patient‐reported outcomes were collected through voluntary follow‐up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. Results: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow‐up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self‐esteem. Treatment‐related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. Conclusion: Based on patient‐reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real‐world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil. [ABSTRACT FROM AUTHOR]

Presents a study which looked at changes in zymogen granule size after exposure to known regulators of secretion. Detailed information on the methodology used to conduct the study; Discussion based on the results of the study.

With increased popularity of decorative tattoos, awareness of tattoo‐based dermatological complications has been raised. Health issues include a broad spectrum dominated by allergies and infections. To examine the etiopathology and prognose the outcome of an appropriate therapy, a non‐invasive intravital diagnostic approach is indicated. The present pilot study introduces multiphoton tomography equipped with fluorescence lifetime imaging as a diagnostic technique to examine the morphological and metabolic status of tattooed human skin at patient's bedside. The distributing course of tattoo particles can be visualised over time. By providing optical biopsies, inflammation‐based alterations in freshly tattooed skin and tattoo complications can be analysed. The study concludes that multiphoton tomography combined with fluorescence lifetime imaging is a suitable technique for in vivo visualisation of tattoo pigments as well as for the assessment of quantitative and qualitative skin changes after injection of tattoo ink into human skin. [ABSTRACT FROM AUTHOR]

Calciphylaxis is a rare and potentially life-threatening disease which occurs most frequently in end-stage renal disease. Here, we describe a 69-year-old male patient who presented to the clinic with extremely painful necrotic ulcers of the right lower extremity. His risk factors included hypertension, diabetes mellitus type II, steatosis hepatis, and chronic hepatitis B. Laboratory studies revealed no signs for uremia, hyperparathyroidism, and normal phosphorus as well as calcium levels. A diagnosis of nonuremic calciphylaxis was made in correlation with clinical and histological features. A novel therapeutic approach combining sodium thiosulfate and iloprost showed remarkable improvement of the wound-associated pain and healing of the ulcers within 3 months. Due to its high mortality rate, an early diagnosis and initiation of treatment are crucial to be beneficial for patient outcomes. [ABSTRACT FROM AUTHOR]

A quiz concerning the diagnosis for a disease that shows an acute disseminated erythematous papulovesicular skin lesions in a 7-year-old girl is presented.

Background: It has been demonstrated that von Willebrand factor (VWF) mediated platelet-endothelium and platelet-platelet interactions are shear dependent. The VWF's mobility under dynamic conditions (e.g. flow) is pivotal to platelet adhesion and VWF-mediated aggregate formation in the cascade of VWF-platelet interactions in haemostasis. Results: Combining microfluidic tools with fluorescence and reflection interference contrast microscopy (RICM), here we show, that specific deletions in the A-domains of the biopolymer VWF affect both, adhesion and aggregation properties independently. Intuitively, the deletion of the A1-domain led to a significant decrease in both adhesion and aggregate formation of platelets. Nevertheless, the deletion of the A2-domain revealed a completely different picture, with a significant increase in formation of rolling aggregates (gain of function). We predict that the A2-domain effectively 'masks' the potential between the platelet glycoprotein (GP) Ib and the VWF A1-domain. Furthermore, the deletion of the A3-domain led to no significant variation in either of the two functional characteristics. Conclusions: These data demonstrate that the macroscopic functional properties i.e. adhesion and aggregate formation cannot simply be assigned to the properties of one particular domain, but have to be explained by cooperative phenomena. The absence or presence of molecular entities likewise affects the properties (thermodynamic phenomenology) of its neighbours, therefore altering the macromolecular function. [ABSTRACT FROM AUTHOR]

Background: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune‐related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C‐reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI. Objective: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients. Methods: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non‐responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow‐up was 1.5 and 1.7 years for Cohorts 1 and 2. Results: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non‐responders (n = 32) with a progression‐free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non‐responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non‐responders (n = 16) the log‐rank analysis showed a significant difference between OS and recurrence‐free survival (RFS) curves (p = 0.046 and p = 0.049). Conclusion: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non‐responders. [ABSTRACT FROM AUTHOR]

Background: Pulsed‐dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed. Aims: To compare the efficacy and safety of the variable‐sequenced, large‐spot 532 nm KTP laser to the 595 nm PDL in treating rosacea. Materials and Methods: A prospective, controlled, evaluator‐blinded study. Patients were treated with either a KTP or PDL with 1–3 sessions at intervals of 6–8 weeks. A follow‐up visit was scheduled on Week 6 post‐treatment. Clinical outcome was assessed by computer‐assisted analysis and by patients and two blinded dermatologists. Pain intensity during treatment and adverse events were documented. Results: Forty‐five patients (mean age 51 years) were allocated in a 2:1 ratio to either the KTP or PDL. Erythema in both treatment arms decreased significantly (p < 0.01). Clinical evaluation revealed high improvement. Mean pain intensity was significantly lower with the KTP (2.5/10) than with the PDL (4.1/10). Both lasers showed a good safety profile. Relevant purpura was only seen in the PDL group. Conclusions: Both the variable‐sequenced, large‐spot KTP and the PDL demonstrated comparable efficacy in treatment of rosacea. Regarding safety, the KTP exhibited fewer post‐treatment reactions. The KTP might serve as a potential alternative to PDL in the treatment of rosacea. [ABSTRACT FROM AUTHOR]

Background: Pulsed dye lasers (PDL) are currently the first‐line treatment of port‐wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed. Objectives: To compare clinical outcomes of a variable‐sequenced, long‐pulsed 532‐nm potassium titanyl‐phosphate (KTP) laser and PDL on treating PWB. Methods: A prospective, randomized, split‐side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6–8 weeks. A follow‐up visit was scheduled 6 weeks post‐treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post‐treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented. Results: A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1–5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post‐treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures. Conclusion: Our data indicate that the KTP laser of the latest generation with large‐spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298). [ABSTRACT FROM AUTHOR]

This article discusses the use of neoadjuvant therapy with pembrolizumab, an immune checkpoint inhibitor, in the treatment of acrolentiginous melanoma. The article presents a case study of a 79-year-old female patient with a confirmed lymph node metastasis of melanoma. The patient underwent neoadjuvant treatment with pembrolizumab, which resulted in regression of the primary tumor and the metastasis, allowing for the avoidance of amputation. The article highlights the potential benefits of neoadjuvant immunotherapy in reducing the need for mutilating surgery and preserving function. However, it also notes that not all patients respond to neoadjuvant therapy, and further research is needed in this area. [Extracted from the article]

Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample. The study demonstrates the benefit of a combined analysis of ctDNA and CTC counts in melanoma patients, revealing that CTC subsets and ctDNA provide synergistic real-time information on the mutational status, RNA and protein expression of melanoma cells in individual patients, in relation to clinical outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: In this prospective cohort study of metastatic melanoma patients receiving immune checkpoint inhibitors, we identified a serum chemokine CCL20 increase at baseline with a significantly impaired progression-free and overall survival and as an independent negative prognostic factor for PFS and OS in univariate as well as in multivariate analysis. CCL20 may represent a novel blood biomarker for the prediction of prognosis in advanced melanoma under immunotherapy with a special emphasis on progression. Background: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. Methods: In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes. Results: An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2–6 months) vs. 11 months (95% CI: 6–26 months)) (p = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25–3.12, p = 0.004) and multivariate (HR: 1.99, 95% CI 1.21–3.29, p = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, p = 0.042) with an HR of 1.85 (95% CI 1.02–3.37, p = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02–3.88, p = 0.043). Conclusions: CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 78-year-old Caucasian man who was diagnosed with Sweet's syndrome or acute febrile neutrophilic dermatosis. It notes the patient's history of coronary heart condition and hypertension. It mentions that the Sweet's syndrome should be regarded in lesion's differential diagnosis.

The article presents a case study of a 17-year-old German girl who presented with painless hyperkeratoses of the palms, soles, and feet. She underwent skin biopsy for specimen collection and for light microscopy and ultrastructure analysis from her plantar lesion. She was later diagnosed with Cole disease. The article discusses skin diseases, dermatology, and biopsy.

Background:There is a high demand for dermatological care in Germany. As use of teledermatology has increased significantly, this study aimed to investigate the impact of teledermatology on patient care. Methods:This retrospective cross-sectional study used data from a direct-to-consumer teledermatology platform using store-and-forward technology available in Germany between July 2021 and April 2022. Additional patient characteristics were collected using a voluntary follow-up questionnaire, 28 days after teleconsultation. Results:Data of 1,999 enrolled patients were evaluated. Patients had a mean age of 36 years, and 61.2% (1,223/1,999) lived in a rural residence. The most common diagnoses included eczema (36.0%, 701/1,946), fungal diseases (15.4%, 299/1,946), and acne (12.5%, 243/1,946). The follow-up questionnaire was answered by 166 patients (8.3%, 166/1,999). In total, 42.8% (71/166) of patients had undergone no previous medical consultation. The most frequent reason for using teledermatology was the waiting time for a dermatology outpatient appointment (62.0%, 103/166). A total of 62.0% (103/166) participants rated the treatment success as good or very good, while 86.1% (143/166) rated the quality of telemedical care as equal or better to that of an outpatient visit. Conclusion:This study showed that patients often use teledermatology because of functional barriers (waiting times). In this cohort, the diagnoses strongly corresponded to reasons for outpatient presentation. Most patients rated the quality of teledermatology service as at least equivalent to that of outpatient physician visits and reported treatment success. Thus, teledermatology can relieve the burden of outpatient care while providing high benefits from the patient's perspective. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 32-year-old woman who developed a rare skin condition called indeterminate cell histiocytosis (ICH) after recovering from a COVID-19 infection. ICH is a group of diseases characterized by the proliferation of certain immune cells. The patient's skin lesions initially resolved on their own but later worsened. Treatment with a combination of prednisolone and narrowband ultraviolet B (NB-UVB) light therapy was ineffective, so the patient was switched to bath psoralen plus ultraviolet A (PUVA) therapy, which resulted in a rapid reduction in skin lesions. This case suggests that systemic PUVA therapy may be an effective treatment option for generalized ICH. [Extracted from the article]

Background: Adherence to dermatological treatment is described as poor. Empathy and open communication in the physician–patient relationship has been proven to improve adherence. As direct-to-consumer teledermatology enables patients to access dermatological consultations without in-person interactions, we hypothesized treatment adherence in teledermatology to be low. Methods: The objective of the study was to examine treatment adherence in teledermatology. This retrospective cross-sectional study used data from patients treated through a German direct-to-consumer teledermatology platform between July 2021 and April 2022. Additional information was collected through voluntary follow-up questionnaires provided to patients to assess individual treatment success, treatment-related adverse events, and treatment adherence. Results: Data collection included 771 patients; 61.6% (475/771) were women (mean age 35 years). In 46% (355/771), skin disease had been present for <3 months before teleconsultation. Of all patients who answered the follow-up questionnaire (n = 228), 28.5% (65/228) reported treatment-related adverse events, with skin dryness being the most common (56.9%, 37/65). Adverse events resulting in treatment discontinuation were reported in 1.3% (3/228) of all cases. Improvement in skin condition on therapy was described by 75.4% (172/228). In 85.5% (195/228), full treatment adherence was reported. Conclusion: This is the first study worldwide to examine data on treatment adherence in direct-to-consumer-teledermatology. Despite the lack of doctor–patient interaction, the results of our study demonstrate that most patients show high treatment adherence. Possible drivers contributing to high compliance rates could be the high proportion of new-onset skin diseases, the high treatment success of the prescribed therapies, and the low rate of serious adverse events. [ABSTRACT FROM AUTHOR]

This article discusses the successful treatment of non-uremic calciphylaxis, a potentially life-threatening disease, using a combination therapy of sodium thiosulfate, iloprost, and heparin. The article presents a case study of a 63-year-old patient with ulcerations on both lower legs who experienced significant pain reduction and complete healing of the ulcers after undergoing the combination therapy. The article emphasizes the importance of early diagnosis and treatment for calciphylaxis and highlights the need for further studies to evaluate the efficacy of this combination therapy. [Extracted from the article]

Human prepubertal testicular tissues are rare, but organ culture conditions to develop a system for human in vitro-spermatogenesis are an essential option for fertility preservation in prepubertal boys subjected to gonadotoxic therapy. To avoid animal testing in line with the 3Rs principle, organ culture conditions initially tested on human adult testis tissue were applied to prepubertal samples (n = 3; patient ages 7, 9, and 12 years). Tissues were investigated by immunostaining and transmission electron microscopy (TEM), and the collected culture medium was profiled for steroid hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Culture conditions proved suitable for prepubertal organ culture since SSCs and germ cell proliferation could be maintained until the end of the 3-week-culture. Leydig cells (LCs) were shown to be competent for steroid hormone production. Three additional testis tissues from boys of the same age were examined for the number of germ cells and undifferentiated spermatogonia (SPG). Using TEM micrographs, eight tissues from patients aged 1.5 to 13 years were examined, with respect to the sizes of mitochondria (MT) in undifferentiated SPG and compared with those from two adult testicular tissues. Mitochondrial sizes were shown to be comparable between adults and prepubertal boys from approximately 7 years of age, which suggests the transition of SSCs from normoxic to hypoxic metabolism at about or before this time period. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors, which stimulate the patient's own T-cells to attack tumor cells, have revolutionized the treatment of metastatic melanoma. However, not all melanoma patients respond to therapy possibly due to a lack of T-cells present in or entering tumor tissue. It is presumed that eosinophils could aid T-cell-mediated immune response against tumor cells. In order to describe the local association of eosinophils and T-cells within the tumor microenvironment we investigated specific markers for cell type and activation status using immunofluorescence. Additionally, blood measurements were performed to determine the effects of eosinophil count and their activation status on the efficacy of immune checkpoint inhibition. There was a strong correlation between activated eosinophils and T-cells in melanoma. Furthermore, patients with high blood levels of activated eosinophils showed a delayed tumor progression. In the future, eosinophils may serve as prognostic biomarkers as well as novel therapeutic targets in melanoma. Immune checkpoint inhibition (ICI) has yielded remarkable results in prolonging survival of metastatic melanoma patients but only a subset of individuals treated respond to therapy. Success of ICI treatment appears to depend on the number of tumor-infiltrating effector T-cells, which are known to be influenced by activated eosinophils. To verify the co-occurrence of activated eosinophils and T-cells in melanoma, immunofluorescence was performed in 285 primary or metastatic tumor tissue specimens from 118 patients. Moreover, eosinophil counts and activity markers such as eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) were measured in the serum before therapy start and before the 4th infusion of ICI in 45 metastatic unresected melanoma patients. We observed a positive correlation between increased tumor-infiltrating eosinophils and T-cells associated with delayed melanoma progression. High baseline levels of eosinophil count, serum ECP and EPX were linked to prolonged progression-free survival in metastatic melanoma. Our data provide first indications that activated eosinophils are related to the T-cell-inflamed tumor microenvironment and could be considered as potential future prognostic biomarkers in melanoma. [ABSTRACT FROM AUTHOR]

Ingenol mebutate (IM) is highly effective in the treatment of human papillomavirus (HPV)-induced anogenital warts (AGW) leading to fast ablation within hours. However, the exact mode of action is still largely unknown. We performed dermoscopy, in vivo confocal microscopy (CLM), histology, immunohistochemistry, and immunofluorescence to gain insights in mechanisms of IM treatment in AGW. In addition, we used in vitro assays (ELISA, HPV-transfection models) to further investigate in vivo findings. IM treatment leads to a strong recruitment of neutrophils with thrombosis of small skin vessels within 8 h, in a sense of immunothrombosis. In vivo and in vitro analyses showed that IM supports a prothrombotic environment by endothelial cell activation and von Willebrand factor (VWF) secretion, in addition to induction of neutrophil extracellular traps (NETosis). IM superinduces CXCL8/IL-8 expression in HPV-E6/E7 transfected HaCaT cells when compared to non-infected keratinocytes. Rapid ablation of warts after IM treatment can be well explained by the observed immunothrombosis. This new mechanism has so far only been observed in HPV-induced lesions and is completely different from the mechanisms we see in the treatment of transformed keratinocytes in actinic keratosis. Our initial findings indicate an HPV-specific effect, which could be also of interest for the treatment of other HPV-induced lesions. Larger studies are now needed to further investigate the potential of IM in different HPV tumors. [ABSTRACT FROM AUTHOR]

• Heparan sulfate at the surface of melanoma cells promote the binding of von Willebrand factor. • Blood circulating melanoma cells with high heparan sulfate levels are encapsulated by plasmatic von Willebrand factor. • Plasmatic von Willebrand factor at the surface of melanoma cells is anti-metastatic. • Reduced expression of HS by melanoma cells correlate with metastasis and reduced survival. Heparan sulfate (HS), a highly negatively charged glycosaminoglycan, is ubiquitously present in all tissues and also exposed on the surface of mammalian cells. A plethora of molecules such as growth factors, cytokines or coagulation factors bear HS binding sites. Accordingly, HS controls the communication of cells with their environment and therefore numerous physiological and pathophysiological processes such as cell adhesion, migration, and cancer cell metastasis. In the present work, we found that HS exposed by blood circulating melanoma cells recruited considerable amounts of plasmatic von Willebrand factor (vWF) to the cellular surface. Analyses assisted by super-resolution microscopy indicated that HS and vWF formed a tight molecular complex. Enzymatic removal of HS or genetic engineering of the HS biosynthesis showed that a reduced length of the HS chains or complete lack of HS was associated with significantly reduced vWF encapsulation. In microfluidic experiments, mimicking a tumor-activated vascular system, we found that vWF-HS complexes prevented vascular adhesion. In line with this, single molecular force spectroscopy suggested that the vWF-HS complex promoted the repulsion of circulating cancer cells from the blood vessel wall to counteract metastasis. Experiments in wild type and vWF knockout mice confirmed that the HS-vWF complex at the melanoma cell surface attenuated hematogenous metastasis, whereas melanoma cells lacking HS evade the anti-metastatic recognition by vWF. Analysis of tissue samples obtained from melanoma patients validated that metastatic melanoma cells produce less HS. Transcriptome data further suggest that attenuated expression of HS-related genes correlate with metastases and reduced patients' survival. In conclusion, we showed that HS-mediated binding of plasmatic vWF to the cellular surface can reduce the hematogenous spread of melanoma. Cancer cells with low HS levels evade vWF recognition and are thus prone to form metastases. Therefore, therapeutic expansion of the cancer cell exposed HS may prevent tumor progression. [ABSTRACT FROM AUTHOR]

• Loss of PECAM-1 improves outcome in a mouse model of ischemic stroke. • PECAM-1 increases diapedesis of neutrophils in ischemic stroke in vivo and in vitro. • Blocking anti-PECAM-1 antibodies reduces neutrophil infiltration and infarct volume. Adhesion molecules are key elements in stroke-induced brain injury by regulating the migration of effector immune cells from the circulation to the lesion site. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an adhesion molecule highly expressed on endothelial cells and leukocytes, which controls the final steps of trans-endothelial migration. A functional role for PECAM-1 in post-ischemic brain injury has not yet been demonstrated. Using genetic Pecam-1 depletion and PECAM-1 blockade using a neutralizing anti-PECAM-1 antibody, we evaluated the role of PECAM-1 mediated trans-endothelial immune cell migration for ischemic injury, delayed brain atrophy, and brain immune cell infiltrates. Trans-endothelial immune cell migration was furthermore evaluated in cultured human cerebral microvascular endothelial cells. Transient middle cerebral artery occlusion (tMCAO) was induced in 10–12-week-old male Pecam-1 −/− and Pecam-1 +/+ wildtype mice. PECAM-1 levels increased in the ischemic brain tissue due to the infiltration of PECAM-1+ leukocytes. Using magnetic resonance imaging, we observed smaller infarct volume, less edema formation, and less brain atrophy in Pecam-1 −/− compared with Pecam-1 +/+ wildtype mice. The transmigration of leukocytes, specifical neutrophils, was selectively reduced by Pecam-1 −/−, as shown by immune fluorescence and flow cytometry in vivo and transmigration assays in vitro. Importantly, inhibition with an anti-PECAM-1 antibody in wildtype mice decreased neutrophil brain influx and infarct. PECAM-1 controls the trans-endothelial migration of neutrophils in a mouse model of ischemic stroke. Antibody blockade of PECAM-1 after stroke onset ameliorates stroke severity in mice, making PECAM-1 an interesting target to dampen post-stroke neuroinflammation, reduce ischemic brain injury, and enhance post-ischemic brain remodeling. [ABSTRACT FROM AUTHOR]

The glycocalyx regulates the interaction of mammalian cells with extracellular molecules, such as cytokines. However, it is unknown to which extend the glycocalyx of distinct cancer cells control the binding and uptake of nanoparticles. In the present study, exome sequencing data of cancer patients and analysis of distinct melanoma and bladder cancer cell lines suggested differences in cancer cell-exposed glycocalyx components such as heparan sulphate. Our data indicate that glycocalyx differences affected the binding of cationic chitosan nanocapsules (Chi-NCs). The pronounced glycocalyx of bladder cancer cells enhanced the internalisation of nanoencapsulated capsaicin. Consequently, capsaicin induced apoptosis in the cancer cells, but not in the less glycosylated benign urothelial cells. Moreover, we measured counterion condensation on highly negatively charged heparan sulphate chains. Counterion condensation triggered a cooperative binding of Chi-NCs, characterised by a weak binding rate at low Chi-NC doses and a strongly increased binding rate at high Chi-NC concentrations. Our results indicate that the glycocalyx of tumour cells controls the binding and biological activity of nanoparticles. This has to be considered for the design of tumour cell directed nanocarriers to improve the delivery of cytotoxic drugs. Differential nanoparticle binding may also be useful to discriminate tumour cells from healthy cells. [ABSTRACT FROM AUTHOR]

Background: Interferon-alpha is an important therapeutic option for the treatment of the cutaneous T-cell lymphomas (CTCL). Since the approved recombinant interferon-α-2a (IFN-α2a) has no longer been produced since January 2020, pegylated interferon-α2a (pegIFN-α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN-α2a in the treatment of CTCL., Patients and Methods: A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers., Results: In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ± 14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα-2a therapy. In 50% of cases, therapy was discontinued after 63.6 ± 33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently., Conclusions: Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα-2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα-2a appears to be comparable to IFN-α2a therapy., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Skin diseases in patients with skin of colour (Fitzpatrick skin types IV to VI) are underrepresented in dermatology training, which may lead to lower quality of care for these patients. To address this underrepresentation in medical education, a newly developed seminar on skin type diversity using an interactive teaching method was implemented in an undergraduate medical curriculum. This study examined the effects of a seminar on the self-assessed competence of medical students in managing skin conditions in patients with skin of colour., Methods: A questionnaire survey was conducted among fourth-year undergraduate medical students at the University of Hamburg (Germany) between October 2023 and February 2024. Students' self-assessed competence was compared before and after the obligatory seminar (pre- and post-design)., Results: In total, 158 students participated in the survey. After the seminar, knowledge of the presentation of skin diseases in patients with skin of colour and the associated psychological burden, differences in the incidence of skin diseases in different skin types, and the ability to diagnose skin diseases in darker skin types increased. Most participants stated that they wanted to attend more courses on this topic., Discussion: Appropriate courses for medical students can improve their competence in managing different skin diseases in patients with skin of colour. In the future, more attention should be paid to teaching the diversity of skin types in dermatology education., (© 2024. The Author(s).)

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis., (© 2024. The Author(s).)

Background: One of the areas of care in dermatosurgery is the surgical treatment of diseases of the nail organ. Side effects and complications after nail surgery were investigated by telephone follow-up (TFU), and its suitability for postoperative monitoring and consultation was assessed., Patients and Methods: All patients who underwent nail surgery at the Department of Dermatology at the Ludwigshafen City Hospital from October 2019 to December 2021 in outpatient setting were contacted by telephone on the second to third postoperative day and questioned in a standardized manner about postoperative complaints and counselled if necessary., Results: A total of 100 cases were followed up. The most common procedures performed were phenol matricectomy (41%), nail avulsion (16%), and nail matrix biopsies (9%). 50% and 21% of patients reported pain on the day of the procedure and the day after surgery, respectively. After nail avulsion, pain was statistically significantly more frequently reported on the day following the procedure and pain medication was statistically significantly more frequently required (p  =  0.002). Serious adverse events did not occur after nail surgery. 10% of the respondents raised specific questions and needed counseling by TFU., Conclusions: All nail surgeries were well tolerated in the outpatient setting. Pain was the most common side effect, although only half of all patients reported pain on the day of surgery and only 21% on the day after the procedure. The TFU proved to be an effective and practical as well as easy to establish method for postoperative follow-up and consultation after outpatient nail surgery., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Necrobiotic xanthogranuloma is a rare disease that is part of the non-Langerhans cell histiocytoses. It is characterized by yellowish skin lesions, which are typically periorbitally localized. Extracutaneous manifestations of all organs are possible and can cause potentially life-threatening complications. The disease also belongs to the facultative paraneoplasias and is often associated with paraproteinemia. These aspects should be considered regarding further diagnostics. Due to the rarity of the disease, there are no standardized guidelines for therapy so far. The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Objective: The use of direct-to-consumer (DTC) teledermatology platforms has increased, particularly for androgenetic alopecia (AGA). However, little is known about the efficacy and safety of these platforms. This study aimed to investigate the patient-reported treatment outcomes and safety of DTC teledermatology for the finasteride treatment of male AGA., Methods: This retrospective, cross-sectional study used data from a German DTC platform for finasteride treatment between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided to the patients six weeks after the first prescription to assess treatment outcomes and safety., Results: Data collection included 2269 patients. Of all patients who answered the follow-up questionnaire ( n  = 191), 79% (150 out of 191) self-reported positive changes in hair appearance, and 59% (113 out of 191) reported an improvement in self-esteem under treatment. Patients with self-reported positive changes in hair appearance were more likely to report improved self-esteem ( P  < 0.0001). Treatment-related adverse events occurred in 12% (22 out of 191) of the patients. Full treatment adherence was reported in 87% (167 out of 191) of patients., Conclusion: From the patient's perspective, DTC teledermatology has the potential to improve hair appearance and self-esteem. Our results suggest that it may be an effective and safe treatment option for men with AGA, justifying low-threshold access. However, treatment-related adverse events should be closely monitored during follow-up. Further studies are required to evaluate the long-term effects of the DTC teledermatology treatment. By collecting real-world data, teledermatology platforms could be useful beyond their primary focus and could play an important role in the context of future research., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JB, FS, and JV: Employees of Wellster Healthtech Group. JB: Member of the Medical Advisory Board of Wellster Healthtech Group. JB: Stock options. The other authors declare no conflicts of interest., (© The Author(s) 2023.)