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Background Sequential digital dermoscopy (SDD) is applied for early melanoma detection by uncovering dynamic changes of monitored lesions. Convolutional neural networks (CNN) are capable of high diagnostic accuracies similar to trained dermatologists. Objectives To investigate the capability of CNN to correctly classify melanomas originally diagnosed by mere dynamic changes during SDD. Methods A retrospective cross-sectional study using image quartets of 59 high-risk patients each containing one melanoma diagnosed by dynamic changes during SDD and three nevi (236 lesions). Two validated CNN classified quartets at baseline or after SDD follow-up at the time of melanoma diagnosis. Moreover, baseline quartets were rated by 26 dermatologists. The main outcome was the number of quartets with correct classifications. Results CNN-1 correctly classified 9 (15.3%) and CNN-2 8 (13.6%) of 59 baseline quartets. In baseline images, CNN-1 attained a sensitivity of 25.4% (16.1%–37.8%) and specificity of 92.7% (87.8%–95.7%), whereas CNN-2 of 28.8% (18.8%–41.4%) and 75.7% (68.9%–81.4%). Expectedly, after SDD follow-up CNN more readily detected melanomas resulting in improved sensitivities (CNN-1: 44.1% [32.2%–56.7%]; CNN-2: 49.2% [36.8%–61.6%]). Dermatologists were told that each baseline quartet contained one melanoma, and on average, correctly classified 24 (22–27) of 59 quartets. Correspondingly, accepting a baseline quartet to be appropriately classified whenever the highest malignancy score was assigned to the melanoma within, CNN-1 and CNN-2 correctly classified 28 (47.5%) and 22 (37.3%) of 59 quartets, respectively. Conclusions The tested CNN could not replace the strategy of SDD. There is a need for CNN capable of integrating information on dynamic changes into analyses.

Background: Psoriasis is a chronic and systemic inflammatory disease with a loss of up to 5 life years, which is thought to be reduced by biologic treatment. Disease severity and eligibility for systemic treatment are often based on the cutaneous psoriasis area and severity index (PASI) with a cut-off of 10 in several European countries. However, it is unclear how well this cut-off reflects systemic inflammation and, consequently, the risk for the development of comorbidity. Objectives: (1) To assess whether specific PASI thresholds, in particular PASI 10, predict elevated biomarkers of systemic inflammation and cardiovascular risk on an individual patient level. (2) To assess the association of PASI and psoriatic arthritis with biomarkers of systemic inflammation and cardiovascular risk. Methods: Retrospective cross-sectional study of 72 psoriasis patients without systemic treatment. Results: Overall, 68, 42, and 50% of patients had cardiovascular risk level neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, and elevated platelet-to-lymphocyte ratio (PLR) values, respectively. The respective positive predictive values of PASI 10 were 70, 45, and 70. The performance of the optimal PASI cut-offs according to the Youden index was similarly weak. Subgrouping of patients with a PASI below 10 did not result in a considerably improved reflection of systemic inflammation. PLR was significantly higher in patients with moderate-to-severe compared to mild psoriasis and significantly correlated with PASI in patients with a PASI above 2 (rs = 0.266, n = 64). NLR was significantly higher in patients with psoriatic arthritis. Conclusion: Specific PASI thresholds were not well suited to predict elevated biomarkers of systemic inflammation and cardiovascular risk on an individual patient level. Therefore, PASI, and possibly other purely cutaneous measures, may not be ideal as stand-alone parameters to define disease severity and eligibility for systemic treatment. Our results are relevant for the ongoing discussion on the definition of psoriasis severity and eligibility for systemic treatment. Further research addressing the added value of a set of biomarkers of systemic inflammation in the assessment of psoriasis severity would be desirable.

Background Psoriasis is considered an independent cardiovascular risk factor, evidentially driving atherosclerosis. However, little is known about changes in the microvasculature of non-lesional skin in psoriasis patients. This study systematically examined capillary pathologies in psoriasis patients by digital video nailfold capillaroscopy. Patients and methods Prospective study comparing nailfold capillaries of psoriasis patients with those of healthy controls. Nailfold capillaries were evaluated for 21 parameters and results were correlated with characteristics of patients and psoriatic disease, laboratory parameters, and measurements of carotid intima-media thickness. Results 77 psoriasis patients (24 patients with additional psoriatic arthritis) and 71 controls were well-matched for demographic features and for relevant confounding factors causing microangiopathy. In comparison with controls, psoriasis patients showed a significant loss of capillaries, capillary expansion with increased ramifications and tortuosity and capillary irregularities. Moreover, in psoriasis patients we found significantly elevated serum markers of inflammation and significantly increased intima-media-thickness measurements. We found no effect of disease duration nor disease activity on capillary changes. Conclusions Nailfold capillaries of psoriasis patients showed marked microvascular abnormalities accompanied by increased markers of systemic inflammation and atherosclerosis. Prospective cohort studies are needed to assess the role of nailfold capillaroscopy for predicting the cardiovascular risk of psoriasis patients.

Functional skin barrier requires sphingolipid homeostasis; 3-ketodihydrosphingosine reductase or KDSR is a key enzyme of sphingolipid anabolism catalyzing the reduction of 3-ketodihydrosphingosine to sphinganine. Biallelic mutations in the KDSR gene may cause erythrokeratoderma variabilis et progressive-4, later specified as PERIOPTER syndrome, emphasizing a characteristic periorifical and ptychotropic erythrokeratoderma. We report another patient with compound heterozygous mutations in KDSR, born with generalized harlequin ichthyosis, which progressed into palmoplantar keratoderma. To determine whether patient-associated KDSR mutations lead to KDSR substrate accumulation and/or unrecognized sphingolipid downstream products in stratum corneum (SC), we analyzed lipids of this and previously published patients with non-identical biallelic mutations in KDSR. In SC of both patients, we identified ‘hitherto’ unobserved skin ceramides with an unusual keto-type sphingoid base in lesional and non-lesional areas, which accounted for up to 10% of the measured ceramide species. Furthermore, an overall shorter mean chain length of free and bound sphingoid bases was observed—shorter mean chain length of free sphingoid bases was also observed in lesional psoriasis vulgaris SC, but not generally in lesional atopic dermatitis SC. Formation of keto-type ceramides is probably due to a bottle neck in metabolic flux through KDSR and a bypass by ceramide synthases, which highlights the importance of tight intermediate regulation during sphingolipid anabolism and reveals substrate deprivation as potential therapy.

The healing phase of contact hypersensitivity reactions is critically dependent on regulatory T cells (Tregs), but even the early inflammatory phase, that is, 6-24 hours after induction of a contact hypersensitivity reaction, is susceptible to Treg-mediated suppression. To investigate the underlying mechanisms, we injected Tregs before the challenge and analyzed the skin-infiltrating cells as early as 6 hours later. Early on, we found mainly neutrophils in the challenged skin, but only a few T cells. This influx of neutrophils was blocked by the injection of Tregs, indicating that they were able to prevent the first wave of leukocytes, which are responsible for starting an immune reaction. As an underlying mechanism, we identified that Tregs can tighten endothelial junctions by inducing intracellular cAMP, leading to protein kinase A-RhoA‒dependent signaling. This eventually reorganizes endothelial junction proteins, such as Notch3, Nectin 2, Filamin B, and VE-cadherin, all of which contribute to the tightening of the endothelial barrier. In summary, Tregs prevent the leakage of proinflammatory cells from and into the tissue, which establishes a mechanism to downregulate immune reactions.

BACKGROUND AND OBJECTIVES Convolutional neural networks (CNN) enable accurate diagnosis of medical images and perform on or above the level of individual physicians. Recently, collective human intelligence (CoHI) was shown to exceed the diagnostic accuracy of individuals. Thus, diagnostic performance of CoHI (120 dermatologists) versus individual dermatologists versus two state-of-the-art CNN was investigated. PATIENTS AND METHODS Cross-sectional reader study with presentation of 30 clinical cases to 120 dermatologists. Six diagnoses were offered and votes collected via remote voting devices (quizzbox®, Quizzbox Solutions GmbH, Stuttgart, Germany). Dermatoscopic images were classified by a binary and multiclass CNN (FotoFinder Systems GmbH, Bad Birnbach, Germany). Three sets of diagnostic classifications were scored against ground truth: (1) CoHI, (2) individual dermatologists, and (3) CNN. RESULTS CoHI attained a significantly higher accuracy [95 % confidence interval] (80.0 % [62.7 %-90.5 %]) than individual dermatologists (75.7 % [73.8 %-77.5 %]) and CNN (70.0 % [52.1 %-83.3 %]; all P

HINTERGRUND UND ZIELE Systeme kunstlicher Intelligenz (durch "deep learning" faltende neuronale Netzwerke; engl. convolutional neural networks, CNN) erreichen inzwischen bei der Klassifikation von Hautlasionen vergleichbar gute Ergebnisse wie Dermatologen. Allerdings mussen die Limitationen solcher Systeme vor flachendeckendem klinischem Einsatz bekannt sein. Daher haben wir den Einfluss des "dunklen Rand-Artefakts" (engl. dark corner artefact; DCA) in dermatoskopischen Bildern auf die diagnostische Leistung eines CNN mit Marktzulassung zur Klassifikation von Hautlasionen untersucht. PATIENTEN UND METHODEN Ein Datensatz aus 233 Bildern von Hautlasionen (60 maligne und 173 benigne) ohne DCA (Kontrolle) wurde digital so modifiziert, dass kleine, mittlere oder grose DCA zu sehen waren. Alle 932 Bilder wurden dann mittels CNN mit Marktzulassung (Moleanalyzer-Pro® , FotoFinder Systems) auf Malignitatsscores hin analysiert. Das Spektrum reichte von 0-1; ein Score von > 0,5 wurde als maligne klassifiziert. ERGEBNISSE In der Kontrollserie ohne DCA erreichte das CNN eine Sensitivitat von 90,0 % (79,9 %-95,3 %), eine Spezifitat von 96,5 % (92,6 %-98,4 %) sowie eine Flache unter der Kurve (AUC, area under the curve) der "receiver operating characteristic" (ROC) von 0,961 (0,932-0,989). In den Datensatzen mit kleinen beziehungsweise mittleren DCA war die diagnostische Leistung vergleichbar. In den Bildersatzen mit grosen DCA wurden allerdings signifikant hohere Malignitatsscores erzielt. Dies fuhrte zu einer signifikant verminderten Spezifitat (87,9 % [82,2 %-91,9 %], P

ZusammenfassungUnter dem Begriff Pseudolymphom (PSL) versteht man eine benigne, reaktive Lymphoproliferation der Haut, die klinisch und/oder histologisch ein malignes Lymphom simulieren kann. Die genaue Ätiopathogenese ist bis heute nicht gänzlich geklärt. Man unterscheidet die primären, idiopathischen PSL ohne erkennbare Ursache von den sekundären PSL mit bekanntem Stimulus. Wir berichten über das Auftreten von Pseudolymphomen nach einer Behandlung mit medizinischen Blutegeln (Hirudotherapie). Bisher wurden nach bestem Wissen und Gewissen insgesamt nur 9 Fälle von kutanen PSL nach Hirudotherapie in der Literatur beschrieben.

Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment.

The clinical differentiation of face and scalp lesions (FSLs) is challenging even for trained dermatologists. Studies comparing the diagnostic performance of a convolutional neural network (CNN) with dermatologists in FSL are lacking.A market-approved CNN (Moleanalyzer-Pro, FotoFinder Systems) was used for binary classifications of 100 dermoscopic images of FSL. The same lesions were used in a two-level reader study including 64 dermatologists (level I: dermoscopy only; level II: dermoscopy, clinical close-up images, textual information). Primary endpoints were the CNN's sensitivity and specificity in comparison with the dermatologists' management decisions in level II. Generalizability of the CNN results was tested by using four additional external data sets.The CNN's sensitivity, specificity and ROC AUC were 96.2% [87.0%-98.9%], 68.8% [54.7%-80.1%] and 0.929 [0.880-0.978], respectively. In level II, the dermatologists' management decisions showed a mean sensitivity of 84.2% [82.2%-86.2%] and specificity of 69.4% [66.0%-72.8%]. When fixing the CNN's specificity at the dermatologists' mean specificity (69.4%), the CNN's sensitivity (96.2% [87.0%-98.9%]) was significantly higher than that of dermatologists (84.2% [82.2%-86.2%]; p 0.001). Dermatologists of all training levels were outperformed by the CNN (all p 0.001). In confirmation, the CNN's accuracy (83.0%) was significantly higher than dermatologists' accuracies in level II management decisions (all p 0.001). The CNN's performance was largely confirmed in three additional external data sets but particularly showed a reduced specificity in one Australian data set including FSL on severely sun-damaged skin.When applied as an assistant system, the CNN's higher sensitivity at an equivalent specificity may result in an improved early detection of face and scalp skin cancers.

Many studies have addressed the effects of dietary supplementation with soy protein on cancer risk and mortality, but there are only few randomized studies with soy in males. We used serum samples from a two year trial of soy protein isolate supplementation in middle aged to older males at risk of recurrence of prostate cancer after radical prostatectomy to determine soy effects on steroid hormones involved in prostate cancer (testosterone, SHBG, estradiol) and explore the effects on biomarkers of the growth hormone/IGF-1 axis, apoptosis, and angiogenesis. Compared with a casein-based placebo, 18 months of consumption of 19.2 g/day of whole soy protein isolate containing 24 mg genistein reduced circulating testosterone and SHBG, but not free testosterone, and did not affect serum concentrations of estradiol, VEGF, IGF-1, IGFBP-3, IGF-1/IGFBP-3 ratio, soluble Fas, Fas-ligand, and sFas/Fas-ligand ratio. Thus, soy protein supplementation for 18 months affected the androgen axis, but the effects on other cancer biomarkers remain to be more definitively determined. The study was registered at clinicaltrials.gov (NCT00765479).

Background In recent studies, convolutional neural networks (CNNs) outperformed dermatologists in distinguishing dermoscopic images of melanoma and nevi. In these studies, dermatologists and artificial intelligence were considered as opponents. However, the combination of classifiers frequently yields superior results, both in machine learning and among humans. In this study, we investigated the potential benefit of combining human and artificial intelligence for skin cancer classification. Methods Using 11,444 dermoscopic images, which were divided into five diagnostic categories, novel deep learning techniques were used to train a single CNN. Then, both 112 dermatologists of 13 German university hospitals and the trained CNN independently classified a set of 300 biopsy-verified skin lesions into those five classes. Taking into account the certainty of the decisions, the two independently determined diagnoses were combined to a new classifier with the help of a gradient boosting method. The primary end-point of the study was the correct classification of the images into five designated categories, whereas the secondary end-point was the correct classification of lesions as either benign or malignant (binary classification). Findings Regarding the multiclass task, the combination of man and machine achieved an accuracy of 82.95%. This was 1.36% higher than the best of the two individual classifiers (81.59% achieved by the CNN). Owing to the class imbalance in the binary problem, sensitivity, but not accuracy, was examined and demonstrated to be superior (89%) to the best individual classifier (CNN with 86.1%). The specificity in the combined classifier decreased from 89.2% to 84%. However, at an equal sensitivity of 89%, the CNN achieved a specificity of only 81.5% Interpretation Our findings indicate that the combination of human and artificial intelligence achieves superior results over the independent results of both of these systems.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

ZusammenfassungChronische Prurigo ist durch anhaltenden Pruritus, teils einhergehend mit sekundären Kratzläsionen, gekennzeichnet. Die Abklärung der Genese ist von besonderem Stellenwert, wobei eine atopische Diathese häufig einen ätiologischen Faktor darstellt. Wir präsentieren einen Patienten mit chronischem Pruritus multifaktorieller Genese (atopische Diathese, chronische Niereninsuffizienz, Diabetes mellitus, Polyneuropathie). Nach multiplen erfolglosen Vortherapien behandelten wir den Patienten mit Dupilumab, worunter sich ein sehr positiver Erkrankungsverlauf mit deutlicher Besserung der Lebensqualität zeigte.

Background Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies of the skin. Even though most patients are sufficiently treated by surgical resection, some will eventually metastasize and need systemic therapy. Phase I and II studies have shown efficacy for programmed cell death protein 1 (PD-1) inhibitors, but cohort sizes are low and real-world data especially on long-term outcome are pending. Methods Patients from six German skin cancer centers treated with PD-1 inhibitors (pembrolizumab, nivolumab or cemiplimab) for advanced cSCC were retrospectively studied. Internal patient records were analyzed for clinical outcome including response, progression-free survival (PFS), overall survival (OS) and toxicity. Results Of 46 evaluable patients (median age: 76 years), the overall response rate (RR) was 58.7%, including 15.2% with complete response. The disease control rate was 80.4%. Both median PFS and OS were not reached, Kaplan–Meier estimated 1-year PFS was 58.8%. Patients responding to therapy showed durable remission. Response was independent of the PD-1 inhibitor used and also independent of the presence of distant metastases vs. locally advanced disease. Two predictive factors were found: Patients with primaries located on the leg had a poorer therapy outcome and patients with high lactate dehydrogenase serum levels at baseline. Treatment was overall tolerated well, with less than 10% of patients discontinuing therapy due to toxicity. Conclusions PD-1 inhibitors fulfill the need for an efficient systemic therapy for advanced cSCC and should be the new standard of care. With high RRs and durable disease control, neoadjuvant and adjuvant regimens should be evaluated.

ZusammenfassungDie Purpura anularis teleangiectodes (PAT) ist eine seltene Erkrankung aus dem Spektrum der hämorrhagisch pigmentierten Dermatosen, die vorzugsweise junge Frauen betrifft und klinisch durch symmetrische, anuläre Erytheme mit Teleangiektasien an der unteren Extremität imponiert. Histologisch zeigen sich oberflächlich dermal gelegene Erythrozytenextravasate begleitet von einem lymphozytären Entzündungsinfiltrat. Als Auslöser können häufig Medikamente identifiziert werden. In idiopathischen Fällen werden kortisonhaltige Externa eingesetzt. Auch eine Kompressionsbehandlung kann unterstützend sinnvoll sein.

Zusammenfassung Die aktuelle SARS‐CoV‐2 Pandemie gefährdet vor allem ältere Menschen mit kardiopulmonalen und metabolischen Vorerkrankungen. In aktueller Diskussion ist jedoch auch, ob Patienten unter immunsuppressiver Therapie ebenfalls ein höheres Risiko haben, im Fall einer COVID‐19‐Erkrankung einen schweren Krankheitsverlauf zu erleiden. Grundsätzlich gibt es derzeit jedoch keine Datenlage für eine generelle Reduktion oder Pausierung einer Immunsuppression bei Patienten mit Autoimmunerkrankungen in Zeiten der SARS‐CoV‐2‐Pandemie. Da es jedoch derzeit weder eine wirksame Therapie, noch einen entsprechenden Impfschutz gibt, sollten wir uns gezielt mit der Problematik chronisch‐immunsupprimierter Patienten beschäftigen. Um Risiken für Patienten zu minimieren, sollte die Indikation für eine solche Therapie mit besonderer Sorgfalt gestellt werden. Insbesondere sollten Immuntherapeutika, die langfristige Effekte erzeugen (zum Beispiel Rituximab) mit besonderer Vorsicht eingesetzt werden. Demgegenüber könnten immunmodulierende Substanzen, die keine Immunsuppression induzieren (zum Beispiel systemische Immunglobuline, Doxycyclin) oder die intrinsische Wirkungen auf SARS‐CoV‐2 haben (Calcineurininhibitoren, Chloroquin, Hydroxychloroquin), eine sinnvolle Alternative darstellen.

ZusammenfassungTätowierungen inklusive Permanent-Make-up können diverse Komplikationen wie virale oder bakterielle Infektionen sowie allergische und entzündliche Reaktionen nach sich ziehen. Bei Letzteren weist die Histologie neben exogenem Pigment ein Entzündungsinfiltrat auf, das je nach Reaktionsmuster lymphozytär oder histiozytär-granulomatös dominiert sein kann. Nachfolgend wird über die erfolgreiche Therapie mittels intraläsionaler Triamcinolonacetonid-Injektionen bei granulomatöser Entzündungsreaktion nach Tätowierungen in 2 Fällen berichtet.

Livedo is a net-like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as 'livedo racemosa'. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions.

Background Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. Objectives To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. Methods The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). Results HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). Conclusions Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

Universidade Federal de Minas Gerais. Instituto de Ci?ncias Biol?gicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Instituto de Ci?ncias Biol?gicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Pesquisa Cl?nica e Pol?ticas P?blicas em Doen?as Infecciosas e Parasit?rias. Belo Horizonte, MG, Brazil. Universidade Federal do Esp?rito Santo. Centro de Ci?ncias da Sa?de. N?cleo de Doen?as Infecciosas. Vit?ria, ES, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Diagn?stico e Terapia de Doen?as Infecciosas e Oncol?gicas. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Pesquisa Cl?nica e Pol?ticas P?blicas em Doen?as Infecciosas e Parasit?rias. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Instituto de Ci?ncias Biol?gicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Instituto de Ci?ncias Biol?gicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Instituto de Ci?ncias Biol?gicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil. Due to the efforts to control schistosomiasis transmission in tropical countries, a large proportion of individuals from endemic areas present low parasite loads, which hinders diagnosis of intestinal schistosomiasis by the Kato-Katz (KK) method. Therefore, the development of more sensitive diagnostic methods is essential for efficient control measures. The aim was to evaluate the accuracy of a real-time polymerase chain reaction (RT-PCR) to detect Schistosoma mansoni DNA in fecal samples of individuals with low parasite loads. A cross-sectional population-based study was conducted in a rural community (n = 257) in Brazil. POC-CCA? was performed in urine and feces were used for RT-PCR. In addition, fecal exams were completed by 18 KK slides, saline gradient and Helmintex techniques. The combined results of the three parasitological tests detected schistosome eggs in 118 participants (45.9%) and composed the consolidated reference standard (CRS). By RT-PCR, 117 out of 215 tested samples were positive, showing 91.4% sensitivity, 80.2% specificity and good concordance with the CRS (kappa = 0.71). RT-PCR identified 86.9% of the individuals eliminating less than 12 eggs/g of feces, demonstrating much better performance than POC-CCA? (50.8%). Our results showed that RT-PCR is a valuable alternative for the diagnosis of intestinal schistosomiasis in individuals with very low parasite loads.

Zusammenfassung Hintergrund und Ziele Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hoch dosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg-Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Da der Einsatz von IVIg als Therapie der ersten Wahl aufgrund der hohen Kosten begrenzt ist, wurden erste klinische Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet. Patienten und Methoden Die europäischen Leitlinien wurden von einer Gruppe durch das EDF („European Dermatology Forum“) und die EADV („European Academy of Dermatology and Venereology“) benannter Experten erarbeitet. Die Leitlinien wurden erstellt, um die derzeit als wirksam erachteten Behandlungsindikationen zu aktualisieren und die Evidenz der für die Anwendung von IVIg bei dermatologischen Autoimmunerkrankungen und TEN vorliegenden Daten zusammenzufassen. Ergebnisse und Schlussfolgerung Die vorliegenden Leitlinien repräsentieren die einvernehmliche Meinung und Definitionen von Experten zur Anwendung von IVIg, die die aktuell publizierten Daten widerspiegeln, und sollen als Entscheidungshilfe für den Einsatz von IVIg bei dermatologischen Erkrankungen dienen.

Background Deep learning convolutional neural networks (CNNs) show great potential for melanoma diagnosis. Melanoma thickness at diagnosis among others depends on melanoma localisation and subtype (e.g. advanced thickness in acrolentiginous or nodular melanomas). The question whether CNN may counterbalance physicians’ diagnostic difficulties in these melanomas has not been addressed. We aimed to investigate the diagnostic performance of a CNN with approval for the European market across different melanoma localisations and subtypes. Methods The current market version of a CNN (Moleanalyzer-Pro®, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used for classifications (malignant/benign) in six dermoscopic image sets. Each set included 30 melanomas and 100 benign lesions of related localisations and morphology (set-SSM: superficial spreading melanomas and macular nevi; set-LMM: lentigo maligna melanomas and facial solar lentigines/seborrhoeic keratoses/nevi; set-NM: nodular melanomas and papillomatous/dermal/blue nevi; set-Mucosa: mucosal melanomas and mucosal melanoses/macules/nevi; set-AMskin: acrolentiginous melanomas and acral (congenital) nevi; set-AMnail: subungual melanomas and subungual (congenital) nevi/lentigines/ethnical type pigmentations). Results The CNN showed a high-level performance in set-SSM, set-NM and set-LMM (sensitivities >93.3%, specificities >65%, receiver operating characteristics-area under the curve [ROC-AUC] >0.926). In set-AMskin, the sensitivity was lower (83.3%) at a high specificity (91.0%) and ROC-AUC (0.928). A limited performance was found in set-mucosa (sensitivity 93.3%, specificity 38.0%, ROC-AUC 0.754) and set-AMnail (sensitivity 53.3%, specificity 68.0%, ROC-AUC 0.621). Conclusions The CNN may help to partly counterbalance reduced human accuracies. However, physicians need to be aware of the CNN's limited diagnostic performance in mucosal and subungual lesions. Improvements may be expected from additional training images of mucosal and subungual sites.

HINTERGRUND Kombinierte Navi (KN) zeigen zwei oder mehr Komponenten bestimmter Navustypen und stellen klassische Melanomsimulatoren dar. In dieser Studie wurde eine vorab definierte Auswahl dermatoskopischer Merkmale sowie drei diagnostische Algorithmen hinsichtlich der Differenzierung von KN und Melanomen evaluiert. PATIENTEN UND METHODIK Retrospektive, verblindete Fallkontrollstudie mit Vergleich dermatoskopischer Bilder von 36 KN sowie 36 Melanomen. Insgesamt wurden 21 dermatoskopische Merkmale, die Anzahl der Farben sowie drei diagnostische Algorithmen (ABCD-Regel, Menzies-Score, 7-Punkte-Checkliste) untersucht. ERGEBNISSE 5 von 7 typischen Navus-Merkmalen wurden signifikant haufiger in KN im Vergleich zu Melanomen gefunden (alle p

Background Chemokine ligand-20 (CCL20) expressed in the epidermis is a potent impetus for the recruitment of CC-chemokine receptor 6 (CCR6)-expressing subsets of DCs, B-cells and memory T-cells into the skin. CCL20 and CCR6+ immune cells have been detected in chronic inflammatory skin diseases and several malignancies, including melanoma. Yet, the functional contribution of the CCR6/CCL20 axis for melanoma progression remains controversial. Objective The functional contribution of CCR6-expressing immune cell subsets and local CCL20 in the tumor microenvironment for the immune control of melanoma was studied. Methods Homeostatic and inducible CCL20 secretion of murine (B16, Ret) and human (A375, C32) melanoma cells was analyzed by ELISA. To assess the functional relevance of CCR6/CCL20 interactions on local tumor progression, prestimulated or retrovirally transduced B16/F1 melanoma cells overexpressing CCL20 (B16-CCL20) were injected subcutaneously into C57BL/6 Wt mice and congenic CCR6-deficient (CCR6−/−) mice. Infiltrating leucocytes were examined by flow cytometry in tumors and draining lymph nodes (DLNs). Results Melanoma cell lines up-regulate CCL20 secretion upon stimulation with pro-inflammatory cytokines in vitro. While only moderate changes in phenotype and composition of leucocytes were detected in advanced tumors and DLNs, mice injected with CCR6+ B16-CCL20 cells developed smaller tumors compared to B16-Control injected littermates, with CCR6-/- mice displaying the most pronounced reduction in tumor growth and incidence. Conclusion Our results suggest that CCR6/CCL20 interactions and individual independent effects of CCL20 and CCR6 in the microenvironment may be essential for melanoma progression and suggest a decisive role of this chemokine axis for melanoma pathogenesis beyond chemoattraction.

Hintergrund und studienziele Korperbehaarung konnte Arzte bei der dermatoskopischen Untersuchung beeintrachtigten. Es ist daher denkbar, dass die Entwicklung eines automatisierten Haarentfernungsalgorithmus (automated-hair-removal-algorithm [AuHRA]) die diagnostische Genauigkeit verbessert. Allerdings wurde bisher weder untersucht wie stark genau die Beeintrachtigung der Arzte durch Korperbehaarung ist, noch wie gros der Nutzen von AuHRA ist. Ziel dieser Studie ist, die Beeintrachtigung durch Korperbehaarung bei der dermatoskopischen Untersuchung zu analysieren und das Ausmas der Verbesserung der Sichtbarkeit von dermatoskopischen Strukturen nach der Anwendung der AuHRA-Software bei digitalen Bildern von haarbedeckten Navi zu evaluieren. Patienten und methodik In dieser Studie beurteilten sechs Dermatologen insgesamt 59 Bildersets, die dermatoskopische Aufnahmen von benignen Navi beinhalteten. Jedes Set umfasste jeweils drei Aufnahmen desselben Navus (unrasiert / mechanisch rasiert / virtuell rasiert mittels AuHRA). Die Aufnahmen wurden im Hinblick auf den Grad der Verbesserung durch Haarentfernung beurteilt. Ergebnisse Im Vergleich zu unrasierten Lasionen bewerteten die Dermatologen die mechanisch rasierten Lasionen als am besten beurteilbar (+1.36, p Schlussfolgerungen Eine erhebliche Beeintrachtigung der dermatoskopischen Untersuchung durch Korperbehaarung wurde in dieser Studie bestatigt. Ein klinischer Nutzen der virtuellen Rasur durch AuRHA im Vergleich zu unrasierten oder mechanisch rasierten Lasionen konnte gezeigt werden.

In an ideal setting, physician‒scientists combine clinical practice and knowledge with scientific curiosity and research in synergy. Li et al. address the current challenges regarding the rare breed of physician‒scientists in the United States–much similar to those faced in German dermatology departments. The authors discuss multiple angles to transform the so-called leaky pipeline into a streamline of dermatologists in science.

Die digitalisierte Bildverarbeitung hat in den vergangenen Jahren grose Fortschritte erzielt. Erste Systeme zur automatisierten Bildanalyse basierten auf mehrstufigen Algorithmen des Maschinenlernens. Diese wurden inzwischen zu selbstlernenden neuronalen Netzwerken weiterentwickelt. Solche auf kunstlicher Intelligenz (KI) basierenden Systeme werden zunehmend auch in der Medizin eingesetzt. Die Dermatologie bietet sich durch die einfache Zuganglichkeit der Hautoberflache fur eine KI-basierte Diagnosestellung durch Bildanalyse an. Innerhalb der Dermatologie nimmt die Hautkrebsdiagnostik einen zentralen Stellenwert ein. Dermatoskopische Aufnahmen von pigmentierten und nichtpigmentierten Hautveranderungen sind in grosen offentlichen Datenbanken verfugbar und konnen so zum Training automatisierter Diagnosesysteme eingesetzt werden. In Studien zur Hautkrebsdiagnostik erzielten verschiedene KI-basierte Systeme eine diagnostische Genauigkeit, welche mit der von erfahrenen Dermatologen vergleichbar war. Ein erstes neuronales Netzwerk zur Hautkrebsdiagnostik anhand von dermatoskopischen Bildern ist zwischenzeitlich fur den europaischen Markt zugelassen worden (Moleanalyzer pro®, FotoFinder Systems GmbH). Auch in der Dermatohistopathologie wurden KI-basierte Diagnosesysteme entwickelt und in Studien getestet. Trotz aller Euphorie uber die hohe Leistungsfahigkeit ist es jedoch von essenzieller Bedeutung, auch Limitierungen KI-basierter Diagnosesysteme aufzuzeigen. So beeinflussen Bildartefakte wie farbliche Markierungen oder eingeblendete Lineale innerhalb dermatoskopischer Aufnahmen die Bildbeurteilung durch neuronale Netzwerke. Genaue Kenntnisse uber die Limitierungen der neuen Technologie sind entscheidend, um Indikationen und Kontraindikationen von KI-basierten Diagnosesystemen zu bestimmen und die Leistungsfahigkeit weiter zu verbessern. Auch wenn neuronale Netzwerke bereits als Assistenzsysteme fur die Hautkrebserkennung eingesetzt werden, liegen der verantwortungsvolle Umgang mit den Ergebnissen und die abschliesende Therapieentscheidung weiterhin beim klinisch tatigen Arzt.

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Psoriasis is thought to be associated with a reduced life expectancy through systemic inflammation. A comparative, retrospective analysis of neutrophil-to-lympho-cyte ratio, a biomarker of systemic inflammation and cardiovascular risk, under 196 treatments with tumour necrosis factor-α and interleukin-12/23 antagonists was performed. Neutrophil-to-lympho-cyte ratio decreased significantly within 3 months of initiation of treatment and remained stable at reduced levels for at least 33 months. Dynamics were more pronounced and neutrophil-to-lympho-cyte ratio under treatment was lower in patients treated with tumour necrosis factor-α compared with interleukin-12/23 antagonists (geometric mean (95% confidence interval): 2.03 (1.9, 2.1) vs 2.63 (2.2, 3.2), respectively, p = 0.014). tumour necrosis factor-α antagonist treatment and baseline neutrophil-to-lympho-cyte ratio were independent predictors of a median low cardiovascular risk neutrophil-to-lympho-cyte ratio (

BACKGROUND Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects patients' quality of life (QoL). OBJECTIVE To investigate changes in QoL in patients with HS after wide local excision (WLE) and to examine the level of pain, rate of postoperative complications, recurrences, and the time to complete wound closure. METHODS Fifty-five patients were enrolled in this prospective study. All patients underwent WLE of HS, followed by secondary wound healing. Dermatologic Life Quality Questionnaire, pain, and wound size were measured 1 day, 3 weeks, 3 months, and 6 months after surgery. RESULTS Dermatologic Life Quality Questionnaire and pain scores (mean ± SD) improved significantly (both p < .001) from 14.5 ± 7.3 and 3.7 ± 2.8 at baseline to 5.8 ± 6.9 and 0.8 ± 1.7, 6 months postoperatively, respectively. Wounds were closed completely by secondary intention after 4.4 ± 2.8 months. Sixteen patients (29.1%) experienced postoperative complications, local recurrences in the treated sites were observed in 11 patients (20%), and new lesions in untreated sites were observed in 5 cases (9.1%). CONCLUSION Wide local excision significantly improves patients' QoL and pain, and, given its low rate of recurrence and complications, should be considered as a first-line therapy, especially in patients with higher Hurley stages.