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Supplementary Figure Legends 1-2 from Down-regulation of Vascular Endothelial Growth Factor Receptor 2 Is a Major Molecular Determinant of Proteasome Inhibitor–Mediated Antiangiogenic Action in Endothelial Cells

Supplementary Figure 2 from Down-regulation of Vascular Endothelial Growth Factor Receptor 2 Is a Major Molecular Determinant of Proteasome Inhibitor–Mediated Antiangiogenic Action in Endothelial Cells

Supplementary Figure 1 from Down-regulation of Vascular Endothelial Growth Factor Receptor 2 Is a Major Molecular Determinant of Proteasome Inhibitor–Mediated Antiangiogenic Action in Endothelial Cells

The ubiquitin-proteasome system is the major pathway for intracellular protein degradation in eukaryotic cells. This system controls a wide range of cellular regulatory proteins, including transcription factors and cell cycle regulatory proteins. Recent evidence also established the importance of the proteasome in tumor development, showing antitumor and antiangiogenic actions by using selective inhibitors in vivo. As signaling via the vascular endothelial growth factor receptor 2 (VEGFR2) pathway is critical for angiogenic responses to occur, we explored whether antiangiogenic effects due to proteasome inhibition were partly mediated through decreased endothelial VEGFR2 expression. This study shows that different proteasome inhibitors blocked VEGFR2 expression in a time-dependent and concentration-dependent manner. This blockade was paralleled by the respective inhibition of the formation of capillary-like structures and endothelial cell migration. In contrast, neither tie-2 nor VEGFR1 expression was significantly affected by proteasome inhibitor treatment. The suppressive effects on VEGFR2 expression were not conveyed by increased shedding or a decrease in protein half-life, suggesting that transcriptional mechanisms accounted for the observed effects. In line with this conclusion, proteasome inhibition significantly suppressed VEGFR2 mRNA accumulation. In addition, inhibitor treatment considerably decreased the transcriptional activity of 5′ deletional VEGFR2 promoter gene constructs. Proteasome inhibition–mediated repression was controlled by a GC-rich region that harbored one consensus Sp1-binding site. Subsequent EMSA analyses showed decreased constitutive Sp1-dependent DNA binding in response to proteasome inhibition. In addition, we could show that proteasome inhibitors reduced VEGFR2 mRNA stability. Therefore, VEGFR2 expression may constitute a critical molecular target of proteasome inhibitors that may mediate their antiangiogenic effects in vivo. [Cancer Res 2009;69(5):1976–84]

Hautkrankheiten werden in Deutschland stationär vorwiegend in den 115 Hautkliniken versorgt.Versorgungswissenschaftliche und gesundheitsökonomische Analyse der dermatologischen stationären Versorgung und Prädiktion des zukünftigen Versorgungsbedarfes auf der Basis von Primär- und Sekundärdaten.Die ambulante und stationäre Versorgung der dermatologischen Behandlungsindikationen wird überwiegend durch Fachärzte für Dermatologie getragen. Stationär wurden 2018 833 491 Fälle behandelt, entsprechend 4,21 % aller stationären Fälle (19 808 687). Häufigste Behandlungsfälle waren: epithelialer Hautkrebs (gesamt 87 386, davon dermatologische Kliniken 52 608), gefolgt von Melanom (23 917/17 774), Psoriasis (19 291/13 352), Erysipel (73 337/11 260), sonstige Dermatitis (12 671/10 842), atopisches Ekzem (11 421/9734) und Herpes zoster (26 249/9652). Mit einer durchschnittlichen Verweildauer von 5,69 Tagen befanden sich die dermatologischen Kliniken im unteren Drittel. Der Anteil der in Hautkliniken versorgten stationären Indikationen war am höchsten bei Prurigo (95,2 %), Pemphigus (94,9 %), Parapsoriasis (94,6 %), Pemphigoid (90,3 %), Dermatitiden (85,6 %) und atopischem Ekzem (85,2 %). Während die Gesamtzahl der stationären Behandlungsfälle in Deutschland zwischen 2000 und 2018 um durchschnittlich 17,5 % gestiegen ist, ist dies bei Hautkrankheiten zu 26,6 % der Fall, bei einzelnen zu über 150 %. Die Projektion der heutigen auf die zukünftige stationäre Versorgung lässt einen weiterhin hohen Bedarf an stationärer Versorgung durch die Hautkliniken erwarten.Die stationäre dermatologische Versorgung ist auch zukünftig ein unerlässlicher Bestandteil der qualifizierten, sozialrechtlich notwendigen Versorgung in Deutschland.

Background In Germany, skin diseases are mainly treated in the 115 dermatological hospitals. Methods Health care and health economic analysis of dermatological inpatient care and prediction of future care needs based on primary and secondary data. Results Outpatient and inpatient care for dermatologic treatment indications is predominantly provided by dermatology specialists. Inpatient treatment was provided for 833,491 cases in 2018, corresponding to 4.21 % of all inpatient cases (19,808,687). Most common treatment cases were: epithelial skin cancer (total 87,386, of which dermatology clinics 52,608), followed by melanoma (23,917/17,774), psoriasis (19,291/13,352), erysipelas (73,337/11,260), other dermatitis (12,671/10,842), atopic dermatitis (AD) (11,421/9,734), and herpes zoster (26,249/9,652). With an average length of stay of 5.69 days, dermatology hospitals were in the bottom third. The proportion of inpatient indications cared for in dermatology hospitals was highest for prurigo (95.2 %), pemphigus (94.9 %), parapsoriasis (94.6 %), pemphigoid (90.3 %), eczema other than AD (85.6 %), and AD (85.2 %). While the total number of inpatient treatment cases in Germany has increased by an average of 17.5 % between 2000 and 2018, this is the case for 26.6 % of skin diseases and over 150 % for individual ones. The projection of current to future inpatient care suggests a continued high demand for inpatient care by dermatology hospitals. Conclusion Inpatient dermatological care will continue to be an indispensable component of qualified, socially necessary care in Germany.

Background No simple staging system has emerged for basal cell carcinomas (BCCs), since they do not follow the TNM process, and practitioners failed to agree on simple clinical or pathological criteria as a basis for a classification. Operational classification of BCCs is required for decision‐making, trials and guidelines. Unsupervised clustering of real cases of difficult‐to‐treat BCCs (DTT‐BCCs; part 1) has demonstrated that experts could blindly agree on a five groups classification of DTT‐BCCs based on five patterns of clinical situations. Objective Using this five patterns to generate an operational and comprehensive classification of BCCs. Method Testing practitioner's agreement, when using the five patterns classification to ensure that it is robust enough to be used in the practice. Generating the first version of a staging system of BCCs based on pattern recognition. Results Sixty‐two physicians, including 48 practitioners and the 14 experts who participated in the generation of the five different patterns of DTT‐BCCs, agreed on 90% of cases when classifying 199 DTT‐BCCs cases using the five patterns classification (part 1) attesting that this classification is understandable and usable in practice. In order to cover the whole field of BCCs, these five groups of DTT‐BCCs were added a group representing the huge number of easy‐to‐treat BCCs, for which sub‐classification has little interest, and a group of very rare metastatic cases, resulting in a four‐stage and seven‐substage staging system of BCCs. Conclusion A practical classification adapted to the specificities of BCCs is proposed. It is the first tumour classification based on pattern recognition of clinical situations, which proves to be consistent and usable. This EADO staging system version 1 will be improved step by step and tested as a decision tool and a prognostic instrument.

Johannes Kleemann, Manuel Jäger, Eva Valesky, Stefan Kippenberger, Roland Kaufmann, Markus Meissner Department of Dermatology, Venerology and Allergology, University Hospital, Goethe University, Frankfurt am Main, GermanyCorrespondence: Johannes KleemannDepartment of Dermatology, Venereology and Allergy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, GermanyTel +4969 6301 5179Fax +49 69 6301 5117Email johannes.kleemann@kgu.dePurpose: Rising melanoma incidences lead to an increasing need for individual therapy strategies in old patients. Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, approved for the local treatment of unresectable metastatic melanoma. Since data on the efficacy and safety of geriatric patients are sparse, this study was conducted to gain further real-world experience in the treatment of old and oldest-old patients with T-VEC and to obtain data on therapy costs in this population in Germany.Patients and Methods: We performed a retrospective analysis, including all patients with a minimum age of 75 years who were treated with T-VEC from August 2016 to September 2020 in the Skin Cancer Center of the University Hospital Frankfurt, Germany. Patient clinicopathological data, treatment responses, toxicities, treatment-specific data and therapy costs were assessed.Results: Twelve patients with a median age of 83 years (75– 89 years) at the start of treatment were identified. By the end of the study, three (25%) patients experienced complete remission (CR), four (33%) experienced partial response (PR), two patients (17%) remained at stable disease (SD) and three (25%) patients suffered from progressive disease (PD). Overall response rate was 58.3%, and durable response rate was 41.7%. There were no treatment-related adverse events grade 3 or higher. The median duration of treatment was seventeen weeks (3– 57 weeks). Median medication costs in the patients who had completed treatment (n=10) were calculated to be 27,325 Euros in Germany.Conclusion: This study provides further evidence for an effective use of T-VEC in old and oldest-old patients. The low rate of adverse events seems to be favorable compared to other systemic melanoma therapies. Furthermore, duration of treatment was short and therapy costs were lower than would have been expected from clinical trial data. Altogether, these data encourage the use of T-VEC in this special patient cohort.Keywords: intralesional therapy, immunotherapy, oncolytic virus, advanced melanoma, cutaneous oncology, elderly patients

In the basal, proliferative layer of healthy skin, the mTOR complex 1 (mTORC1) is activated, thus regulating proliferation while preventing differentiation. When cells leave the proliferative, basal compartment, mTORC1 signaling is turned off, which allows differentiation. Under inflammatory conditions, this switch is hijacked by cytokines and prevents proper differentiation. It is currently unknown how mTORC1 is regulated to mediate these effects on keratinocyte differentiation. In other tissues, mTORC1 activity is controlled through various pathways via the tuberous sclerosis complex (TSC). Thus, we investigated whether the TS complex is regulated by proinflammatory cytokines and contributes to the pathogenesis of psoriasis. TNF-α as well as IL-1β induced the phosphorylation of TSC2, especially on S939 via the PI3-K/AKT and MAPK pathway. Surprisingly, increased TSC2 phosphorylation could not be detected in psoriasis patients. Instead, TSC2 was strongly downregulated in lesional psoriatic skin compared to non-lesional skin of the same patients or healthy skin. In vitro inflammatory cytokines induced dissociation of TSC2 from the lysosome, followed by destabilization of the TS complex and degradation. Thus, we assume that in psoriasis, inflammatory cytokines induce strong TSC2 phosphorylation, which in turn leads to its degradation. Consequently, chronic mTORC1 activity impairs ordered keratinocyte differentiation and contributes to the phenotypical changes seen in the psoriatic epidermis.

The clinical application of immune checkpoint inhibitors represents a breakthrough progress in the treatment of metastasized melanoma and other tumor entities. In the present study, it was hypothesized that oligonucleotides (ODNs), known as modulators of the immune response, have an impact on the endogenous expression of checkpoint molecules, namely PD-L1 and PD-L2 (PD-L1/2). IFNγ-stimulated melanoma cells (A375, SK-Mel-28) were treated with different synthetically manufactured oligonucleotides which differed in sequence, length and backbone composition. It was found that a variety of different ODN sequences significantly suppressed PD-L1/2 expression. This effect was dependent on length and phosphorothioate (PTO) backbone. In particular, a sequence containing solely guanines (nCpG-6-PTO) was highly effective in downregulating PD-L1/2 at the protein, mRNA and promoter levels. Mechanistically, we gave evidence that ODNs with G-quartet-forming motifs suppress the interferon signaling axis (JAK/STAT/IRF1). Our findings identify a subset of ODNs as interesting pharmacological compounds that could expand the arsenal of targeted therapies to combat the immunological escape of tumor cells.

ZusammenfassungDie Fotoepilation zählt zu den meistgefragten nichtchirurgischen Eingriffen in der ästhetischen Dermatologie. Haarlose, glatte Beine gelten dabei als Schönheitsideal.Fotoepilation mittels Laser oder hochenergetischer Blitzlampen (sog. Intensed-Pulsed-Light-Geräte) stellt ein sicheres und effektives Verfahren dar. Der Wirkmechanismus beruht auf dem Prinzip der selektiven Fotothermolyse, wobei eine gezielte thermische Schädigung pigmentierter Haarfollikel unter Schonung des umliegenden Gewebes erfolgt. Melaninpigment des Haarschaftes absorbiert als Zielchromophor Licht eines speziellen Wellenlängenspektrums und führt durch Wärmediffusion zur Schädigung der für das Haarwachstum wichtigen Stammzellen im äußeren Haarwurzelschaft.Patienten müssen über die Notwendigkeit wiederholter Behandlungen sowie den häufig nur partiellen und temporären Haarverlust aufgeklärt werden. Dunkle Terminalhaare bei hellen Hauttypen lassen sich effektiv entfernen. Bei dunklen Hauttypen besteht aufgrund des erhöhten epidermalen Melaninvorkommens ein erhöhtes Risiko für Nebenwirkungen wie Verbrennungen, Dyspigmentierungen und Narben. Sehr feine, helle oder rote Haare lassen sich kaum mit konventionellen Fotoepilationsverfahren entfernen. Haarentfernungsgeräte für den Heimgebrauch sind eine kostengünstige, einfach anzuwendende Alternative, weisen aber im Vergleich zur professionellen Fotoepilation eine geringere Effektivität auf.

Propofol belongs to a class of molecules that are known to block learning and memory in mammals, including rodents and humans. Interestingly, learning and memory are not tied to the presence of a nervous system. There are several lines of evidence indicating that single-celled organisms also have the capacity for learning and memory which may be considered as basal intelligence. Here, we introduce a new experimental model for testing the learning ability of Physarum polycephalum, a model organism frequently used to study single-celled “intelligence”. In this study, the impact of propofol on Physarum’s “intelligence” was tested. The model consists of a labyrinth of subsequent bifurcations in which food (oat flakes soaked with coconut oil-derived medium chain triglycerides [MCT] and soybean oil-derived long chain triglycerides [LCT]) or propofol in MCT/LCT) is placed in one of each Y-branch. In this setting, it was tested whether Physarum memorized the rewarding branch. We saw that Physarum was a quick learner when capturing the first bifurcations of the maze; thereafter, the effect decreased, perhaps due to reaching a state of satiety. In contrast, when oat flakes were soaked with propofol, Physarum’s preference for oat flakes declined significantly. Several possible actions, including the blocking of gamma-aminobutyric acid (GABA) receptor signaling, are suggested to account for this behavior, many of which can be tested in our new model.

The prevalence of systemic reactions to hymenoptera stings is up to 7.5%. Venom-specific immunotherapy (VIT) is an established treatment for insect venom allergy. In order to monitor the allergic status and thus the success of the therapy, controlled sting challenge under VIT continues to be the gold standard. This review deals not only with useful indications and therapeutic consequences but also with critical aspects that should be considered when performing sting challenge.

Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)—an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma—in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination. Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4+ and CD8+ T-cell immunity.

Purpose Although regular water is composed of two hydrogens and one oxygen, referred to as H2O, a small amount of water on this planet contains alternative forms of elements with different molecular weights because of the addition of neutrons. The present study was dedicated to studying the effect of heavy water (D2O), in which the two hydrogens become substituted by deuterium, on the cell physiology of different human cells with particular focus on malignant melanoma cells. Methods Cells were cultured in regular medium in which the content of H2O was gradually substituted by D2O or deuterium-depleted water (DDW). Following this, the changes of basic cellular parameters, such as morphology, migration, proliferation, cell cycle, apoptosis and microtubule integrity were examined. Results It was found that raising the D2O content above the standard levels led to a concentration-dependent decrease in proliferation. Lowering the D2O levels below this level had no effect. Likewise, elevated D2O levels hampered migration. Moreover, cell-cycle analysis showed an increase of sub-G1 cells. Corroboratively, markers for apoptosis were induced (histone-associated DNA fragments, Bax, and PARP). In regard to microtubule integrity, only very high levels of D2O (75%) caused partial filament condensation. Conclusion D2O, although chemically identical with H2O, shows proapoptotic and antiproliferative effects on melanoma cells. These findings give a closer look of this interesting compound.

BACKGROUND In melanoma, preclinical data suggest a possible role of polyunsaturated fatty acids inhibiting cell growth. A new target molecule for free fatty acids, the G protein-coupled receptor GPR40, was identified in melanoma cells. OBJECTIVES The aim of this study was to investigate GPR40 expression in human melanocytic tissues and to evaluate its potential as a prognostic marker. METHODS AND RESULTS A total of 114 tissue sections of naevi, primary melanoma and melanoma metastasis were immunohistochemically stained with anti-GPR40. The staining was evaluated, using the immunoreactivity scoring system. Compared to naevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR40 (P

Impaired wound healing as well as imbalanced cell proliferation and extracellular matrix synthesis and degeneration can cause aberrant scarring. The most severe impacts of such scarring on patients' lives are stigmatization and physical restriction. Although, a broad variety of combinatorial approaches with, e.g., glucocorticoids, chemotherapeutics, and immunomodulators are used, there is still a high recurrence rate of keloids. The aim of this study was to investigate which influence interferon γ (IFN-γ, 1.000-10.000 IU/mL) and/or triamcinolone acetonide (TA, 1 μg/mL) have on proliferation, cell viability, collagen type I synthesis, and cytokine secretion in healthy and keloid fibroblasts. It was shown that mono-treatment with IFN-γ or TA for 2 days induced a severe reduction of the proliferative potential in both cell species. The combinatory treatment (IFN-γ plus TA) of keloid fibroblasts enhanced the anti-proliferative effect of the mono-treatments, whereas no additional anti-proliferative effect was observed in normal fibroblasts. Furthermore, we observed that the combinatory treatment regimen reduced the expression of α-smooth muscle actin (α-SMA), an actin isotype contributing to cell-generated mechanical tension, in keloid fibroblasts. In normal fibroblasts, α-SMA was reduced by the mono-treatment with IFN-γ as well as by the combinatory treatment. The analysis of collagen-type I synthesis revealed that TA did not reduce collagen type I synthesis in normal fibroblasts but in keloid fibroblasts. IFN-γ reduced in both cell species the collagen type I synthesis. The combination of TA and IFN-γ intensified the previously observed collagen type I synthesis reduction in keloid fibroblasts. The herein presented data suggest the combinatory application of IFN-γ and TA as a promising therapy concept for keloids.

A satisfying history match of CO2 plume migration in the Sleipner field of the Utsira formation has been difficult to achieve using multiphase flow simulations. Poor modeling of plume or reservoir temperature and impurities in the CO2 stream have been cited as a source of uncertainty in model predictions. Both of these aspects can have a large impact on the simulation results of plume migration in the Sleipner field where the injected fluid is close to the critical point of CO2. We have performed multiphase flow simulations in the uppermost sand layer of the Sleipner field (Layer 9) over a range of temperatures and fluid compositions in order to clarify these uncertainties. The results reveal that an increase in temperature by a few degrees and simultaneously accounting for impurities from the separation process lead to significantly improved comparison with seismic data. Between temperature and fluid composition, temperature was the most important predictor for success. The results of this study imply that the impact of temperature on model predictions has previously been underestimated. Implementation of a realistic temperature and fluid composition will lead to better prediction of plume mobility and storage capacity, which is important for screening and planning of optimal storage sites.

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

Experimental findings indicated that 2-methoxyestradiol (2-ME), an endogenous metabolite of 17β-estradiol, may exhibit anti-tumorigenic properties in various types of tumour, such as melanoma and endometrial carcinoma. In patients with endometrial cancer, the serum levels of 2-ME are decreased compared with those in healthy controls, and this finding has been associated with a poor outcome. The aim of the present study was to examine whether the serum levels of 2-ME are decreased in patients with melanoma, and whether this decrease may be correlated with disease stage and, therefore, serve as a prognostic indicator. ELISA was used to detect serum levels of 2-ME in patients with stage I-IV malignant melanoma (MM). A cohort of 78 patients with MM was analysed, along with 25 healthy controls, among whom 15 were women in the second trimester of pregnancy (positive control). As expected, significantly elevated levels of serum 2-ME were observed in pregnant control patients compared with those in patients with MM and healthy controls. There was no observed correlation between 2-ME serum levels in patients with MM and disease stage, tumour thickness, lactate dehydrogenase or S100 calcium-binding protein B levels. In addition, the 2-ME levels of patients with MM did not differ significantly from those of normal healthy controls. Overall, the findings of the present study indicated that the 2-ME serum levels in patients with MM were not decreased, and there was no correlation with early- or advanced-stage disease. Therefore, in contrast to published results on endometrial cancer, endogenous serum 2-ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.

Background and Objectives: Hidradenitis suppurativa (HS) and plaque psoriasis (Pso) are supposed to have a coprevalence. However, data showing a more detailed description of patients with both diseases are rare. In this study, we characterized patients with both skin diseases in terms of onset, disease course, severity, concomitant diseases and therapeutical management. Patients and Methods: Data from 28 patients with a confirmed codiagnosis of HS and Pso from 2 university hospitals presented between 2015 and 2019 were evaluated retrospectively. For further characterization, patients were divided into different cohorts depending on whether HS or Pso was diagnosed as the first disease. Results: The average age of patients with a coprevalence of both diseases was 44.4 years with a female/male ratio of 1:1.15. Fifteen patients were diagnosed first with HS at an average age of 22.8 years, 13 patients first showed symptoms of Pso at a mean age of 21.7 years. The average time to the onset of the corresponding second disease was 14.3 years. Patients with HS as first disease showed a significantly severer form of HS compared to patients with a first diagnosis of Pso (mean highest International Hidradenitis Suppurativa Severity Score System: 23.5 vs. 8.2; p = 0.02). Severity of psoriatic disease in patients with HS at first diagnosis was numerically lower but not significant compared to the cohort with Pso at first diagnosis (mean highest Psoriasis Area and Severity Index: 7.8 vs. 13.2; p = 0.299). The most frequent comorbidity in all patients was obesity (64.3%; mean body mass index: 32.2) followed by psychiatric complaints (25%) and psoriatic arthritis (21.4%). Adalimumab was the most commonly used drug that had a positive effect on both diseases, HS and Pso. Conclusions: In patients with a coprevalence of HS and Pso, the disease which occurs first appears to take a severer course, with an increased risk of development of obesity and psychiatric comorbidity in both cohorts.

Background: Moderate-to-severe plaque psoriasis can be treated very successfully with systemic therapies. Often the therapeutics must be injected subcutaneously. This prospective observational study aimed to compare the correct preparation and performance of subcutaneous injections in trained and untrained patients with plaque psoriasis.Materials and Methods: We asked 110 patients (29.1% women, 70.9% men, injection system: 75.5% prefilled syringe, 24.5% autoinjector) to what extent they were trained for self-injection. While participants injected a sham injection with their current system, we evaluated the preparation, execution, and follow-up using a newly developed scoring system.Results: 87.3% (n = 96) of the participants declared that they had been trained for self-injection. No statistically significant difference was observed between the trained and untrained participants in performing the injection correctly (p = .458). The most common mistakes were the wrong preparation and follow-up of the injection. A bifactorial rank-variance analysis showed a negative influence of the factor injection system (prefilled syringe) on the total score (p = .005).Conclusion: We can indicate that patients with plaque psoriasis are well prepared for subcutaneous self-injection. Self-injection of systemic therapies is easy to perform, especially with patient-friendly systems, and does not require specialized training.

Background The aim of this study was to verify the validity of clinical history and oral provocation challenges of patients with NSAID hypersensitivity and to identify safe alternatives. The COX-2 inhibitor etoricoxib, in particular, was studied. Patients and methods In all, 104 patients with confirmed diagnoses of NSAID hypersensitivity treated at the Department of Dermatology, Frankfurt University Hospital, Germany between 2004 and 2012 were retrospectively studied. Results The medical history and hypersensitivity symptoms during oral provocation testing (OPT) largely coincided and were mostly mild to moderate. Acetylsalicylic acid (ASA) was the most frequent trigger both anamnestically (27.9 %) and during OPT (47.8 %). Etoricoxib caused the fewest reactions during OPT (4.2 %). Acetaminophen led to reactions in only 6.7 % of the cases studied although it was named more often in clinical histories (14 %). Conclusions OPT should be the aim whenever possible as most symptoms are mild to moderate. To distinguish between selective and cross-hypersensitivity reactions, ASA should be part of the test protocol. Furthermore, the findings of this study indicate that etoricoxib and acetaminophen are safe treatment alternatives in case of NSAID hypersensitivity. However, these drugs should not be administered without prior OPT in an inpatient setting, as severe symptoms can occur.

ZusammenfassungDie Sandbox-Dermatitis ist eine weitestgehend unbekannte Erkrankung im Kindesalter, deren Prävalenz wahrscheinlich häufiger ist als angenommen. Wir berichten über den Fall eines 6-jährigen Jungen, der sich mit juckenden, stecknadelkopfgroßen, hypopigmentierten Papeln an den Streckseiten der Extremitäten, die seit den Sommermonaten bestünden, vorstellte. Da der Juckreiz für den Jungen sehr quälend war und die Eltern sich sehr besorgt zeigten, erfolgte die Vorstellung durch den Kinderarzt. Zur Diagnosefindung wurden Differenzialdiagnosen nach ihrer Lokalisation, Morphologie und nach saisonalem Auftreten bewertet. Anhand der typischen Klinik konnte die Diagnose der Sandbox-Dermatitis gestellt werden und dem kleinen Patienten weitere schmerzhafte Diagnostik erspart bleiben. Aufgrund der Einordnung war es nun möglich, eine adäquate Therapie einzuleiten und den Eltern die Sorge zu nehmen, da nun über die Harmlosigkeit, die Triggerfaktoren und den variablen Verlauf der Erkrankung aufgeklärt werden konnte.

Hintergrund In der 1994 erschienen Erstpublikation zur frontal fibrosierenden Alopezie (FFA) fasste Steven Kossard sechs Patientinnen, die sich allesamt in der Postmenopause befanden, zusammen. Bei der FFA handelt es sich um eine vernarbende Alopezie, die durch die klinischen Kriterien der frontotemporalen Haarlinienregression und den Verlust der Augenbrauen gekennzeichnet ist. In letzten Jahren wurden zunehmend Fallberichte zur Manifestation in der Pramenopause und bei mannlichen Patienten publiziert. Ziel der arbeit Zusammenfassung und Analyse der verfugbaren Literatur in Pubmed zur FFA bezuglich der Epidemiologie, der Begleiterkrankungen, der Krankheitsprasentation, Diagnostik und Therapie. Material und methoden Die Datenbank Pubmed wurde nach Fallberichten und Fallserien zur FFA durchsucht. Insgesamt wurden 68 Artikel mit insgesamt 932 Patientenfallen eingeschlossen, analysiert und die patientengebundenen Daten ausgewertet. Neben den epidemiologischen Haufigkeiten wie Alter, Geschlecht oder Ethnie wurden zusatzliche Aspekte zu Pradilektionsstellen, assoziierten Hautveranderungen, Begleiterkrankungen, Medikationen und Therapieansprechen sowie die diagnostische Relevanz von Autoantikorpern erfasst. Ergebnisse Teilweise konnten die in Fallserien und Einzelfallberichten publizierten Erkenntnisse bestatigt und besser differenziert werden, wohingegen einzelne Annahmen nicht reproduziert werden konnten. Von besonderer Relevanz ist die in unserer Analyse ermittelte hohe Koinzidenz der FFA mit Schilddrusenerkrankungen. Schlussfolgerungen Die vorliegende Arbeit prasentiert, die bislang umfangreichste Zusammenfassung der in der Literatur zur FFA publizierten Patientenfalle.

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0-10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0-12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0-12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy.

Physical and chemical emergencies are often caused by household or work accidents. Regardless of the medical field and outside specialized clinics, the physician may be confronted with the situation for first or secondary care. The identification of the causing agent and a rapid assessment of the extent and severity of the tissue damage are essential to initiate early transfer to a specialized burn clinic. Grade 2b tissue damage is usually surgically treated. Smaller and superficial injuries can often be conservatively treated. Even supposedly safe and over-the-counter medicines can also lead to serious tissue damage.

ZusammenfassungDie Livedovaskulopathie (LV) ist eine Erkrankung der kleinen Gefäße der Haut, bei der es durch Thromben zu Gefäßverschlüssen kommt. Klinisch präsentieren die Patienten eine Livedo racemosa und schmerzhafte Ulzerationen, die narbig als Atrophie blanche abheilen. Mit der Erkrankung vergesellschaftet sind häufig Störungen der Gerinnung mit Hyperkoagulabilität, aber auch Autoimmunerkrankungen und Neoplasien. Eine gründliche Diagnostik sollte daher bei bestehendem Verdacht auf eine LV durchgeführt werden. Wir präsentieren hier den Fall eines jungen Mannes mit LV, der neben einer Faktor V Leiden-Mutation, ein Antiphospholipid-Syndrom und einen Embryonalzelltumor des Hodens aufwies.