Search

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]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: 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. [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]

Laser‐assisted drug delivery (LADD) is a treatment method to enhance the penetration of pharmaceuticals through the skin. The aim of the present study is to track hyaluronic acid (HA) and analyse its effect on human skin in vivo after ablative fractional laser (AFL) treatment. Healthy male and female subjects were recruited. Four areas were marked on their forearms of each volunteer, and each area was assigned to one of the following treatment options: AFL + HA, AFL only, HA only or untreated control. A carbon dioxide laser was used for the AFL treatment. Follow‐up measurements were scheduled 30 min and 30 days after treatment using multiphoton tomography equipped with fluorescence lifetime imaging (MPT‐FLIM). A total of 11 subjects completed the study. By detecting fluorescence lifetimes, the HA and the anaesthetic ointment were clearly distinguishable from surrounding tissue. After AFL treatment, HA could be visualized in all epidermal and upper dermal layers. In contrast, HA in intact skin was only detected in the superficial layers at distinctly lower levels. The applied HA gel seemed to have beneficial properties for the wound healing process after laser treatment. LADD has proven to be a fast and effective method to increase HA uptake into the skin, allowing for improved hydration and skin rejuvenation over time. Furthermore, LADD could be a beneficial treatment option in laser resurfacing. MPT‐FLIM proved to be an appropriate diagnostic tool for drug delivery tracking and monitoring of treatment response for individualized therapy adjustment. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

Simple Summary: The interactions between circulating tumor cells (CTCs) and plasma proteins are critical for hematogenous metastasis, and understanding the molecular mechanisms behind these interactions can improve liquid-biopsy-based diagnostics and cancer therapies. This review summarizes recent literature on the surface molecules of CTCs that interact with coagulation proteins and their biological and clinical relevance. It also discusses future research directions to expand our knowledge of the CTC interactome, which can lead to the discovery of new molecular markers for diagnostics and additional targets for cancer therapies. Cancer metastasis is a complex process. After their intravasation into the circulation, the cancer cells are exposed to a harsh environment of physical and biochemical hazards. Whether circulating tumor cells (CTCs) survive and escape from blood flow defines their ability to metastasize. CTCs sense their environment with surface-exposed receptors. The recognition of corresponding ligands, e.g., fibrinogen, by integrins can induce intracellular signaling processes driving CTCs' survival. Other receptors, such as tissue factor (TF), enable CTCs to induce coagulation. Cancer-associated thrombosis (CAT) is adversely connected to patients' outcome. However, cancer cells have also the ability to inhibit coagulation, e.g., through expressing thrombomodulin (TM) or heparan sulfate (HS), an activator of antithrombin (AT). To that extent, individual CTCs can interact with plasma proteins, and whether these interactions are connected to metastasis or clinical symptoms such as CAT is largely unknown. In the present review, we discuss the biological and clinical relevance of cancer-cell-expressed surface molecules and their interaction with plasma proteins. We aim to encourage future research to expand our knowledge of the CTC interactome, as this may not only yield new molecular markers improving liquid-biopsy-based diagnostics but also additional targets for better cancer therapies. [ABSTRACT FROM AUTHOR]

Purpose: The number of online prescription platforms (OPPs) offering telemedical diagnosis and treatment, including finasteride, for androgenetic alopecia (AA) by using medical questionnaires (MQs) has increased. This type of care delivery differs completely from traditional forms. This study aimed to investigate a potential paradigm shift in AA treatment by measuring the extent of traffic generated by OPPs that exclusively treat AA and furthermore by characterizing sociodemographic features of men undergoing finasteride treatment from an OPP in Germany. Patients and Methods: Examination of three OPPs (Keeps, Shapiro MD, Myspring), offering finasteride treatment via MQ between Q1 2018 and Q1 2022 was performed by using SEMRush, a marketing software platform for traffic analysis. Further data regarding sociodemographic characteristics were collected from Myspring by recruiting men with AA who obtained finasteride prescriptions between March 2021 and January 2022. Results: A high number of unique quarterly visitors was recorded. The number of visitors increased on all platforms (Keeps 846%, Shapiro MD 109%, Myspring 427%). Most patients had accessed the platforms from mobile devices. Further data from Myspring included a total of 2904 men. Of all patients who answered the follow-up questionnaire (n =  177), 33.9% had been referred to the platform by television advertising. Of all respondents, 21.5% reported a monthly net income below 1000 euros. 45.2% of responding patients reported being single, while 15.3% considered themselves homosexual, and 4.5% bisexual. Convenience was the most common reason indicated for using an OPP (79.1%). Conclusion: The tremendous increase in the number of visits to OPPs for AA suggests a paradigm shift in medical care, particularly regarding MQ-based finasteride treatment. Sociodemographic data and reasons for platform use suggest that the shift away from traditional care models may increase in the future. The broad use of these digital health services warrants further investigation, particularly regarding patient safety. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objectives: Skin diseases are a common reason for consultations in pediatric practice. The present study aims to characterize the dermatological requests of resident pediatric specialists using teledermatology in Germany. Patients and Methods: This analysis of consultation requests, submitted by pediatricians to a designated pediatric dermatologist via a telemedical consultation system (PädExpert) using the store‐and‐forward technology, was performed between February 2021 and December 2021. Results: The study analysis included 504 telemedical consultation requests. The mean age of the patients was 6.5 ± 5.0 years with 45.5% of the patients being female. Telemedicine was useful in providing a definite diagnosis in 88.3%. The diagnoses were most frequently assigned to the group of infectious skin diseases (28.8%). Referral to a dermatologist was recommended in 11.5%. The requests were answered on the same day in 63.8% of the cases. Conclusions: The study data shows the great potential of teledermatology to improve access for children with skin diseases to specialized dermatological care. Another advantage is its function as a triage instrument. Since most cases could be managed by teledermatology only, it is possible to reduce the need for an in‐person visit to the dermatologist, thus saving resources. [ABSTRACT FROM AUTHOR]

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]

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]

A 66-year-old female patient presented with erythematous skin lesions and neuropathic pain on her lower back and left thigh. Initially, the patient was treated for herpes zoster, but her symptoms persisted and she developed leg paresis and hypesthesia. Further examination and testing revealed that the patient had early neuroborreliosis, a neurological manifestation of Lyme borreliosis. Treatment with antibiotics and analgesics led to significant improvement in the patient's symptoms. This case highlights the importance of considering neuroborreliosis in patients with unclear skin lesions and neurological symptoms. [Extracted from the article]

Introduction: The intravascular formation of neutrophil extracellular traps (NETs) is a trigger for coagulation and blood vessel occlusion. NETs are released from neutrophils as a response to strong inflammatory signals in the course of different diseases such as COVID-19, cancer or antiphospholipid syndrome. NETs are composed of large, chromosomal DNA fibers decorated with a variety of proteins such as histones. Previous research suggested a close mechanistic crosstalk between NETs and the coagulation system involving the coagulation factor XII (FXII), von Willebrand factor (VWF) and tissue factor. However, the direct impact of NET-related DNA fibers on blood flow and blood aggregation independent of the coagulation cascade has remained elusive. Methods: In the present study, we used different microfluidic setups in combination with fluorescence microscopy to investigate the influence of neutrophil-derived extracellular DNA fibers on blood rheology, intravascular occlusion and activation of the complement system. Results: We found that extended DNA fiber networks decelerate blood flow and promote intravascular occlusion of blood vessels independent of the plasmatic coagulation. Associated with the DNA dependent occlusion of the flow channel was the strong activation of the complement system characterized by the production of complement component 5a (C5a). Vice versa, we detected that the local activation of the complement system at the vascular wall was a trigger for NET release. Discussion: In conclusion, we found that DNA fibers as the principal component of NETs are sufficient to induce blood aggregation even in the absence of the coagulation system. Moreover, we discovered that complement activation at the endothelial surface promoted NET formation. Our data envisions DNA degradation and complement inhibition as potential therapeutic strategies in NET-induced coagulopathies. [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]

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]

When deciding on systemic therapy for irAE psoriasis, it should be considered that TNF-alpha inhibitors might improve the response to treatment with ICI and thus the prognosis of the tumour disease. Immune checkpoint inhibitors (ICI) have become firmly established in the treatment of malignant melanoma (MM) and have significantly improved prognosis in advanced tumour stages.[[1]] Recently, the anti-programmed death 1 (PD-1) agent Pembrolizumab showed a significant reduction in the risk of disease recurrence for stage IIB or IIC MM.[2] As ICI interferes with immunoregulatory pathways by blocking checkpoints, non-specific activation of the immune system can result in the development of immune-related adverse events (irAE).[3] In patients receiving monotherapy with a PD-1 inhibitor, grade 3 or 4 irAEs occurred in 23% with nivolumab and in 16% with pembrolizumab.[[1]] The spectrum of cutaneous irAE is diverse and most commonly present as maculopapular exanthema with pruritus.[[3]] Another possible manifestation is psoriasis.[5] Treatment with biologics has been established in the therapy of severe psoriasis, one option being tumour necrosis factor (TNF)-alpha inhibitors.[6] Inflammatory signals such as TNF are essential factors that determine the aggressiveness of melanoma cells.[7] There is evidence that concomitant therapy with a TNF-alpha inhibitor may have positive effects on treatment response and thus tumour prognosis.[8] We report on a 67-year-old man with stage IIB MM. In the further course, the psoriasis was progressive; therefore, therapy with Nivolumab was terminated after six times at the patient's request. [Extracted from the article]

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]

The microenvironment of malignant melanomas defines the properties of tumor blood vessels and regulates infiltration and vascular dissemination of immune and cancer cells, respectively. Previous research in other cancer entities suggested the complement system as an essential part of the tumor microenvironment. Here, we confirm activation of the complement system in samples of melanoma patients and murine melanomas. We identified the tumor endothelium as the starting point of the complement cascade. Generation of complement-derived C5a promoted the recruitment of neutrophils. Upon contact with the vascular endothelium, neutrophils were further activated by complement membrane attack complexes (MACs). MAC-activated neutrophils release neutrophil extracellular traps (NETs). Close to the blood vessel wall, NETs opened the endothelial barrier as indicated by an enhanced vascular leakage. This facilitated the entrance of melanoma cells into the circulation and their systemic spread. Depletion of neutrophils or lack of MAC formation in complement component 6 (C6)-deficient animals protected the vascular endothelium and prevented vascular intravasation of melanoma cells. Our data suggest that inhibition of MAC-mediated neutrophil activation is a potent strategy to abolish hematogenous dissemination in melanoma. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Das kutane Angiosarkom (CAS) ist ein hochaggressiver maligner Tumor mit schlechter Prognose. Das primäre, spontane CAS (pCAS) und das sekundäre, mit einer Bestrahlung oder einem Lymphödem assoziierte CAS (sCAS) unterscheiden sich klinisch sowie molekular. Die Amplifikation/Überexpression von Myc ist ein charakteristisches, wenn auch nicht ausschließliches Merkmal von sCAS, während der Verlust von TP53 selektiv bei pCAS vorkommt. Detaillierte molekulare Analysen mit modernen Multi‐Omics‐Ansätzen haben gezeigt, dass sowohl pCAS als auch sCAS eine erhebliche molekulare Heterogenität aufweisen. Die betroffenen Gene und ihre molekularen Regulatoren sind mögliche therapeutische Zielstrukturen. Darüber hinaus kann das pCAS in Cluster mit hoher Mutationsrate und/oder ausgeprägten Entzündungssignaturen eingeteilt werden, die als Grundlage für die künftige Stratifizierung von pCAS‐Patienten in immuntherapeutischen klinischen Studien dienen können. Während die Aufklärung der der Erkrankung zugrunde liegenden molekularen Veränderungen zügig voranschreitet, verläuft die Entwicklung daraus abgeleiteter neuer Therapien für das CAS jedoch bisher eher langsam. Dennoch wurden einige über die Standardtherapien wie Operation und Radiochemotherapie hinausgehende klinische Studien zu neuen Behandlungsmöglichkeiten initiiert. Dazu gehören zielgerichtete Therapien gegen VEGF und VEGFR1–3 wie Bevacizumab und Pazopanib, sowie β‐Adrenozeptorenblocker wie Propranolol. Derzeit werden auch Immuntherapien entwickelt, unter anderem unter Verwendung der Immuncheckpoint‐Inhibitoren Pembrolizumab und Nivolumab sowie des Anti‐RANKL‐Antikörper Denosumab. [ABSTRACT FROM AUTHOR]

Summary: Cutaneous angiosarcoma (CAS) is a highly aggressive cancer with a poor prognosis. Primary, spontaneous CAS (pCAS) and secondary, post‐irradiation‐ or lymphedema‐associated CAS (sCAS) are clinically, but also molecularly distinct. Myc amplification/overexpression is a characteristic, although not exclusive feature of sCAS, while loss of TP53 selectively occurs in pCAS. Detailed molecular analyses with modern multi‐omics approaches have revealed that both pCAS and sCAS exhibit considerable molecular heterogeneity. Affected genes and their molecular regulators including a plethora of microRNAs may serve as future drug targets. Furthermore, pCAS could be subdivided into clusters with high tumor mutational burden and/or high tumor inflammation signatures providing a rationale for the stratification of pCAS patients in future immunotherapeutic clinical studies. Development of novel treatment regimens guided by these molecular alterations, however, cannot fully keep up with the pace of their discovery due to the low incidence of the disease. Nevertheless, beyond conventional surgery and chemoradiotherapy, clinical trials investigating novel treatment options have been initiated including targeted therapies against VEGF and VEGFR1–3 such as bevacizumab and pazopanib, and β‐adrenoreceptor blockers such as propranolol. Finally, immunotherapies are being developed including immune checkpoint inhibitors pembrolizumab and nivolumab as well as anti‐RANKL antibody denosumab. [ABSTRACT FROM AUTHOR]

Advanced cutaneous squamous cell carcinoma (cSCC) encompasses unresectable and metastatic disease. Although immune checkpoint inhibition has been approved for this entity recently, a considerable proportion of cases is associated with significant morbidity and mortality. Clinical, histopathological, and radiological criteria are used for current diagnostics, classification, and therapeutic decision-making. The identification of complex molecular biomarkers to accurately stratify patients is a not yet accomplished requirement to further shift current diagnostics and care to a personalized precision medicine. This article highlights new insights into the mutational profile of cSCC, summarizes current diagnostic and therapeutic standards, and discusses emerging diagnostic approaches with emphasis on liquid biopsy and tumor tissue-based analyses. [ABSTRACT FROM AUTHOR]