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Overview of psoriasis and guidelines of care for the treatment psoriasis with biologics. J Am Acad. Dermatol ; ; 4. Getting under the skin: the inscription of dermatological disease on the self-concept: Indo-Pacific Journal of Phenomenology 6 2 ; 5.

Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continous or paused etanercept treatment over 54 weeks: the CRYSTEL Study.

Efficacy and safety of continous versus paused etanercept treatment in patients with moderate-to-serve psoriasis over 54 weeks: the CRYSTAL study.

Expert Rev Dermatol. Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept.

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Little data have been reported on the prevalence of comorbidities in psoriasis patients of the Austrian population.

Methods: PsoRA is a web-based nationwide database that contains data from patients with psoriasis being treated under daily life conditions outside of clinical trials.

In particular, PsoRA collects data from patients with systemic psoriasis treatments, phototherapy, and selected topical treatments.

Demographics and comorbidities of patients are collected at enrolment. Results: Data from patients females, males who were enrolled at 16 sites in Austria were available for evaluation.

At first treatment cycle, the median age and disease duration were 45 years range, years and 17 years range, years , respectively. The most prevalent comorbidity was hypertension reported in Conclusions: In the PsoRA population, multiple comorbidities are associated with psoriasis.

Data analysis will determine how comorbidities are linked to basic demographics and the selection of anti-psoriatic treatment. The primary outcome was the PASI reduction after 6 weeks.

Results: Thirty patients could be analysed. Noted adverse events were a case of demyelinating disease, a miliary tuberculosis and an angioedema in the infliximab group as well as two cases of recurrent upper respiratory tract infections and one case of erythema multiforme in the adalimumab group.

The patient treated with etanercept did not experience any adverse events and experienced a successful clinical response.

Despite the low number of patients in this study, we can conclude that both infliximab and adalimumab seem to be equally effective in management of BD, presenting no difference in the occurrence of adverse events.

Isolated reports in literature show that gastrointestinal GI disorders specifically have been associated with rosacea, but no systematic studies have been done to explore this particular association.

In this study, our objective was to evaluate GI symptoms and disorders, and worry as they relate to rosacea.

Methods: Eligible cases were 18 years of age and older with a diagnosis of rosacea. Rosacea-free control subjects were age-, sex-, and race-matched to each case.

A study dermatologist completed clinical evaluations. A structured intervieweradministered questionnaire collected detailed information on GI disorders and associated symptoms, and information on demographics, lifestyle factors, and worrying using the Penn State Worry Questionnaire.

The mean standard deviation; SD age of cases was Mean SD duration of disease was Patients had significantly higher odds of having GI symptoms overall estimated OR Significant associations were found between rosacea and gastrointestinal reflux disease GERD 4.

Conclusion: Our data demonstrate that rosacea patients 1 were more likely to have symptoms and disorders of the upper and lower GI tract, and 2 worry significantly more than controls.

Although rosacea, gastrointestinal disorders, and worry represent separate entities, they appear to follow overlapping pathogenic pathways.

Physicians should be aware of these associations in order to provide comprehensive care to patients with rosacea.

The repository spanned 13 years. Dies traf auf keinen der Urticariapatienten zu. Single nucleotide changes are predominantly found in codon 12, 13 and 61 impairing the intrinsic catalytic activity of NRAS, thus preventing physiological cycling of the protein.

Mutant, and thereby constantly active NRAS contributes to tumor initiation, growth, invasion and metastasis, still it has yet been impossible to pharmaceutically target this protein.

Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of RAS.

Even though mutations in codon 12 and 61 can both be considered activating mutations, each mutation has been recognized to affect protein function in a very distinct way; however, little is known about potential differences in signaling resulting from these alterations.

We facilitated, stable isotope labeling by amino acids in cell culture SILAC , titanium dioxide phosphopeptide enrichment, phospho-Y immunoprecipitation and high accuracy mass spectrometry.

Additional analysis included a phosphorylation-motif search for detected phosphorylation sites and a kinase prediction analysis facilitating overrepresented motifs.

Barrier perturbation induces DNA, protein lipid synthesis leading to barrier recovery. So far, efforts to target NRAS directly have been unsuccessful.

Multi-targeted inhibition is preferred due to the crosstalk between pathways and because it can overcome resistance to single agent drugs.

Methods: We tested metformin and trametinib dual therapy on a panel of 16 NRAS mutant cell lines of the following tumor types: melanoma, lung cancer and neuroblastoma.

Two of the melanoma cell lines had acquired resistance to trametinib. We assessed metformin and trametinib combination efficacy using cell viability assays, apoptotic assays, immunoblotting and mouse xenograft models.

Results: Metformin and trametinib dual therapy synergistically reduces cell viability in vitro and xenograft tumor growth in vivo.

This is seen through a reduction of end effector proteins p-S6 and p-ERK. Conclusions: Metformin and trametinib combinations are effective in preclinical models and might be a possible option for treatment of NRAS mutant cancers.

Recently, proteomics has evolved as a powerful method to identify the protein signature of cells and thereby obtain more information about their biological role.

To date, there are only limited mast cell proteome data available, i. Methods: Mast cells were enriched from human abdominal dermis by magnetic separation and purity was evaluated by toluidine blue and tryptase staining.

For proteome analysis isolated and digested peptides were separated using nanoflow UHPLC before analysis in positive ionisation mode and fragmentation using high energy collision-induced dissociation.

Data was analyzed using Proteome discoverer 1. The identified proteins were classified and further analyzed with a database for annotation, visualization and integrated discovery.

The expression of selected proteins, e. CD26, was verified by PCR, antibody arrays and immunostainings of isolated mast cells and in human skin.

The existing proteome data on exocytosis related proteins in LAD-2 cells was confirmed and extended. Additionally we identified several proteins that were significantly higher expressed in mast cells as compared to other skin cells.

One of the proteins found to be highly abundant in dermal mast cells was CD26 dipeptidylpeptidase IV. In follow-up experiments we verified the expression of CD26 on isolated dermal mast cells and on tryptase-positive mast cells within the dermis.

More detailed analysis of the expression and function of CD26 and other proteins identified in mast cells will allow us to further characterize mast cells and their role in health and disease.

It is approved for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida infections including C.

The primary mode of action of voriconazole is the inhibition of fungal cytochrome Pmediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis.

Furthermore, we observed similar results in a human organotypic skin model. Our findings are in accordance with and extend a recent publication by Angeles JGC et al.

J Clin Exp Dermatol Res , In the mouse K1 is absent from skin regions of the ears, soles and the tail where K2 is expressed.

K1 and K2 heterodimerize with K10 to form intermediate filaments. To investigate the biological effects of genetic disturbances of the keratinocyte cytoskeleton, we have generated and characterized mice in which both K2 and K10 are inactivated.

The skin of ears and soles was subjected to histological and gene expression analysis. The ultrastructure of keratinocytes was determined by electron microscopy.

Results: Mice deficient of both K2 and K10 were viable but developed hyperkeratotic epidermis on their ears and soles.

The deletion of the Krt2 and Krt10 genes abolished these proteins and resulted in a massive increase in the amounts of K1 and K K1 and K16 accumulated in the suprabasal layers of the epidermis of these mice, as determined by immunofluorescence analysis.

In summary, this study suggests that the loss of the keratin pair K2:K10 can be partly compensated by the upregulation of K1 and K Although considerable progress has been made in clinical treatment options for malignant melanoma targeting molecules of these pathways, there is still a need to unveil mechanisms involved in these signaling pathways leading to melanoma progression and to improve treatment outcomes for metastatic melanoma patients.

In this study, we assessed gene expression levels of 84 genes involved in each pathway in human primary and metastatic melanoma samples.

Methods: RNA was isolated from frozen tissue samples 1 normal skin, 4 primary tumors, 1 in-transit metastasis, 5 lymphnode- and 5 subcutaneous metastases and used for cDNA synthesis.

DLK1 was found to be one of the most prominently regulated genes with down-regulation in every tumor except for one axillary lymph-node metastasis.

Prominent SFN downregulation was observed in 2 out of 4 primary tumors and every metastasis in comparison with the normal skin sample.

Objectives: To determine drug survival of ustekinumab in daily clinical practice in patients with moderate-to-severe chronic plaque psoriasis.

Methods: The study was conducted as an observational retrospective multicenter study. This nationwide registry contains data from patients with psoriasis treated with systemic and selected topical agents under daily life conditions outside of clinical trials.

In the present study, we analyzed drug survival data from patients treated with ustekinumab between and Results: Data from patients [66 women, men median age at baseline 43 years, range years; median disease duration 16 years, range years ] comprising ustekinumab treatment cycles during patient-years of follow-up were available for analysis.

The median follow-up after initiation of ustekinumab treatment estimated with the reverse-Kaplan-Meier method was 16 months the maximum was 46 months.

At 12, 24 and 36 months with , 47, and 9 ongoing patient treatment cycles, respectively , drug survival to ustekinumab was The observed drug survival rate of ustekinumab was higher than that for adalimumab, etanercept and infliximab i.

Liu, David Piontkowsky, Martin S. Thomas Kocher, J. Narzt, Ionela M. Systemic administration of IL-2 may cause severe side effects, whereas local administration is considered to be a safe alternative.

The lungs are common sites of metastases in melanoma patients causing considerable respiratory problems.

We sought to evaluate the potential anti-tumoral effect of a low dose inhalative IL-2 lh-IL-2 regimen for patients with melanoma lung metastases.

In addition, we explored the prophylactic potential of Ih-IL-2 after surgical removal of lung metastases in a study carried out in an outpatient setting.

Clinical evaluations were carried out monthly and radiological follow-up was performed every third month. Four patients had progression of lung metastases In the Prophylaxis Group, none of the patients developed new lung metastases during lh-IL-2 therapy.

The median follow-up period was 7. In the majority of patients, treatment was well tolerated. Low dose IL-2 inhalation might offer an effective and safe treatment option for lung metastases in melanoma patients.

Additionally, lh-IL-2 may have a prophylactic potential to prevent recurrence in the lungs after pulmonary melanoma metastasectomy.

Administration can easily be performed in an outpatient setting, thus offering an attractive treatment option. Ergebnisse: 73 Patienten beendeten die Studie.

Eine Therapie mit Cetuximab wurde eingeleitet: Pat. Ergebnis: Bereits nach dem zweiten Therapie-Zyklus 12 Infusionen beobachteten wir bei beiden Patienten eine deutliche Reduktion des Tumoren.

Bei Pat. Im behandlungsfreien posttherapeutischen Beobachtungszeitraum von 2 Monaten kam es zu keiner Verschlechterung der lokalen Situation, allerdings entwickelte die Patientin eine akute CLL und verstarb.

Zyklus mehrere Lokalrezidive und disseminierte Lungenmetastasen und verstarb an der Grundkrankheit. Zusammenfassung: Unsere Beobachtungen zeigen, dass die Kombinationstherapie mit Cetuximab und Celebrex eine hervorragende Alternative in der Behandlung inoperabler kutaner Plep Ca, insbesondere bei multimorbiden Patienten darstellt.

Literatur: Jalili, A. Methods: The aim of this study was to analyze cutaneous melanoma incidence and Breslow tumor thickness in central Alpine mountain region of South Tyrol, northern Italy.

From Pathology Unit, Bolzano Hospital and South Tyrol Cancer Registry, all newly diagnosed cutaneous in situ and invasive melanomas in the resident population from to were retrieved.

Incidence and Breslow tumor thickness were analyzed. Statistical analyses included Mann-Whitney and Kruskal-Wallis tests.

Results: A total of in situ melanomas and invasive melanomas were collected. Overall European-age standardized melanoma incidence raised from In situ melanomas showed the highest increase from 2.

Invasive melanoma incidence increased from The incidence rise was observed in thin melanomas from 8. Breslow distribution revealed a median value of 0.

Incidence of cutaneous melanoma is increasing in South Tyrol, especially for in situ and thin lesions, but also for thick lesions; no reduction in median tumor thickness is observed.

Probably rural areas and elevated altitudes may contribute to this effect. Derzeit sind 2 Mutationen in diesem Gen im Zusammenhang mit dem Melanom beschrieben: c.

R24C und c. Anamnestisch hat er eine negative Familienanamnese. Die Rolle dieser Transkriptionsfaktoren wurde in anderen Krebserkrankungen wie dem nicht kleinzelligen Lungenkarzinom beschrieben.

Die andere Mutation, c. VL liegt im Exon 4, einer Protein-codierenden Region. Sie wurde bei einer Frau mit einer positiven Familienanamnese Vater sowie einem 0,8mm dickem Melanom, an welchem sie mit dem Lebensjahr erkrankt ist, gefunden.

Beide Regionen wiesen eine hohe Konservierung auf. Only few data are available on the role of mast cells in primary cutaneous T-cell lymphomas CTCL , a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin.

The purpose of this study was to quantify the distribution of mast cells in CTCL variants and clinical stages. Methods: Immunohistochemistry with a monoclonal anti-mast cell tryptase antibody was performed on formalin-fixed, paraffin-embedded biopsies of 40 patients with different CTCL variants and on control skin samples.

Results: Mast cells were detected in 37 out of 40 cases. In CTCL mast cell density was higher in areas with tumor infiltration than in surrounding dermis.

With the application of image segmentation methods for mast cell quantification on whole-slide digitized sections allowing reproducible and unbiased cell identification, our results strongly implicate a contribution of mast cells to the pathophysiology of CTCL and provide an initial basis for further research on their use as target for therapeutic intervention.

Little data is available on the role of mast cells in primary cutaneous T-cell lymphomas CTCL , a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin.

The aim of the development was to establish a new tissue analysis method on virtual slides for skin sections stained with immunohistochemistry.

The analysis method was designed to set results into a structural context of cell location and of morphological appearance reflecting a certain state of mast cell activation.

Mast cell degranulation was estimated based on the number of connected brown spots for each cell.

In addition, an algorithm for the automatic detection of the area of the epidermis was developed, as well as density based CTCL areas.

Furthermore distance between each cell and its closest CTCL area was calculated. Up to mast cells per sample were found in dermis area between 1 and 49mm2.

The presented algorithms provided new data insight of context-based and functional characteristics and could generate surrogate markers for further stratification of CTCL.

In melanoma, the amount of VEGF-C expression, tumour lymphangiogenesis and metastasis to sentinel lymph nodes shows a striking correlation.

Methods: We approached this issue by selecting 22 human melanoma cell lines from primary tumours, skin, lymph node and brain metastasis with a wide spectrum of constitutive VEGF-C production.

We correlated VEGF-C, with expression of target genes of various cell signalling pathways, using the gene expression arrays from these cell lines.

The modulation of the cell signalling pathways was performed with various kinase inhibitors as well as with plasmid constructs.

To substantiate this finding, melanoma cells were treated with various kinase inhibitors targeting components of the MAPK-pathways.

Similar results were obtained when this kinase pathway activity was inhibited with lentiviral shRNA constructs.

Eisendle 1 1 Department of Dermatology, Venereology and Allergology. MAC most often presents as a scar-like papule or plaque on sun-exposed skin and is characterized by aggressive local infiltration, including a high propensity for perineural invasion.

Histologically it might be easily confused with benign adnexal tumours, especially when punch biopsies are performed and first wrong diagnoses of trichoepithelioma, trichoadenoma and syringoma often lead to inappropriate initial treatment.

Tissue invasion by MAC frequently extends far beyond the clinical margins of the tumor recurrence is high.

Although metastasis and death from MAC are rare events, significant morbidity can occur as a result of deep local tissue destruction.

Complete surgical removal of the tumour is the treatment of choice. Recent preliminary studies point to higher cure rates with Mohs micrographic surgery.

A year-old healthy female presented with an almost 3 year history of an asymptomatic slowly progressing skin mass on her left eyebrow.

On examination there was a firm nodule measuring 2. Cervical lymphadenopathy was absent. Two deep punch biopsies 4 mm showed a poorly circumscribed, deeply infiltrative tumour with basaloid aspect and perineural invasion confirming MAC.

The patient underwent surgical excision with 1. Histopathology revealed an lateraly and deep incomplete removed tumor R1 infiltrating the muscle bundles with perineural invasion.

A second stage surgery was necessary with lateral and deep enlarging of the defect including the removal of the frontal periostium.

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Carmeliet, P. Kirchhof, L. Schultheiss Berlin , W. Herbsttagung vergeben. Ein Preisrichterkuratorium, bestehend aus den drei Vorsitzenden der Sitzung, wird aus diesen 6 Postern die drei besten Poster aussuchen.

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Kubis, O. Schumacher, R. Schmitt, S. Reppel, H. Liang, J. Hescheler, H. Schunkert, H. Weitere Hinweise: siehe Fachinformation.

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Neuberger, I. Azone, B. Reil, A. Buob, M. Buhr, O. Rana, E. Saygili, C. Schauerte Aachen P Spectral analysis of heart rate variability in patients with neurally mediated syncope during active standing 4 M.

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Saale P Cardiovascular magnetic resonance imaging CMR in cases of cardiac myxoma: localisation, size, morphologic characterization in correlation 2 to post resection histopathologic pattern J.

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Data was analyzed using Proteome discoverer 1. The identified proteins were classified and further analyzed with a database for annotation, visualization and integrated discovery.

The expression of selected proteins, e. CD26, was verified by PCR, antibody arrays and immunostainings of isolated mast cells and in human skin.

The existing proteome data on exocytosis related proteins in LAD-2 cells was confirmed and extended.

Additionally we identified several proteins that were significantly higher expressed in mast cells as compared to other skin cells.

One of the proteins found to be highly abundant in dermal mast cells was CD26 dipeptidylpeptidase IV. In follow-up experiments we verified the expression of CD26 on isolated dermal mast cells and on tryptase-positive mast cells within the dermis.

More detailed analysis of the expression and function of CD26 and other proteins identified in mast cells will allow us to further characterize mast cells and their role in health and disease.

It is approved for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida infections including C.

The primary mode of action of voriconazole is the inhibition of fungal cytochrome Pmediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis.

Furthermore, we observed similar results in a human organotypic skin model. Our findings are in accordance with and extend a recent publication by Angeles JGC et al.

J Clin Exp Dermatol Res , In the mouse K1 is absent from skin regions of the ears, soles and the tail where K2 is expressed.

K1 and K2 heterodimerize with K10 to form intermediate filaments. To investigate the biological effects of genetic disturbances of the keratinocyte cytoskeleton, we have generated and characterized mice in which both K2 and K10 are inactivated.

The skin of ears and soles was subjected to histological and gene expression analysis. The ultrastructure of keratinocytes was determined by electron microscopy.

Results: Mice deficient of both K2 and K10 were viable but developed hyperkeratotic epidermis on their ears and soles.

The deletion of the Krt2 and Krt10 genes abolished these proteins and resulted in a massive increase in the amounts of K1 and K K1 and K16 accumulated in the suprabasal layers of the epidermis of these mice, as determined by immunofluorescence analysis.

In summary, this study suggests that the loss of the keratin pair K2:K10 can be partly compensated by the upregulation of K1 and K Although considerable progress has been made in clinical treatment options for malignant melanoma targeting molecules of these pathways, there is still a need to unveil mechanisms involved in these signaling pathways leading to melanoma progression and to improve treatment outcomes for metastatic melanoma patients.

In this study, we assessed gene expression levels of 84 genes involved in each pathway in human primary and metastatic melanoma samples.

Methods: RNA was isolated from frozen tissue samples 1 normal skin, 4 primary tumors, 1 in-transit metastasis, 5 lymphnode- and 5 subcutaneous metastases and used for cDNA synthesis.

DLK1 was found to be one of the most prominently regulated genes with down-regulation in every tumor except for one axillary lymph-node metastasis.

Prominent SFN downregulation was observed in 2 out of 4 primary tumors and every metastasis in comparison with the normal skin sample. Objectives: To determine drug survival of ustekinumab in daily clinical practice in patients with moderate-to-severe chronic plaque psoriasis.

Methods: The study was conducted as an observational retrospective multicenter study. This nationwide registry contains data from patients with psoriasis treated with systemic and selected topical agents under daily life conditions outside of clinical trials.

In the present study, we analyzed drug survival data from patients treated with ustekinumab between and Results: Data from patients [66 women, men median age at baseline 43 years, range years; median disease duration 16 years, range years ] comprising ustekinumab treatment cycles during patient-years of follow-up were available for analysis.

The median follow-up after initiation of ustekinumab treatment estimated with the reverse-Kaplan-Meier method was 16 months the maximum was 46 months.

At 12, 24 and 36 months with , 47, and 9 ongoing patient treatment cycles, respectively , drug survival to ustekinumab was The observed drug survival rate of ustekinumab was higher than that for adalimumab, etanercept and infliximab i.

Liu, David Piontkowsky, Martin S. Thomas Kocher, J. Narzt, Ionela M. Systemic administration of IL-2 may cause severe side effects, whereas local administration is considered to be a safe alternative.

The lungs are common sites of metastases in melanoma patients causing considerable respiratory problems. We sought to evaluate the potential anti-tumoral effect of a low dose inhalative IL-2 lh-IL-2 regimen for patients with melanoma lung metastases.

In addition, we explored the prophylactic potential of Ih-IL-2 after surgical removal of lung metastases in a study carried out in an outpatient setting.

Clinical evaluations were carried out monthly and radiological follow-up was performed every third month. Four patients had progression of lung metastases In the Prophylaxis Group, none of the patients developed new lung metastases during lh-IL-2 therapy.

The median follow-up period was 7. In the majority of patients, treatment was well tolerated. Low dose IL-2 inhalation might offer an effective and safe treatment option for lung metastases in melanoma patients.

Additionally, lh-IL-2 may have a prophylactic potential to prevent recurrence in the lungs after pulmonary melanoma metastasectomy.

Administration can easily be performed in an outpatient setting, thus offering an attractive treatment option.

Ergebnisse: 73 Patienten beendeten die Studie. Eine Therapie mit Cetuximab wurde eingeleitet: Pat. Ergebnis: Bereits nach dem zweiten Therapie-Zyklus 12 Infusionen beobachteten wir bei beiden Patienten eine deutliche Reduktion des Tumoren.

Bei Pat. Im behandlungsfreien posttherapeutischen Beobachtungszeitraum von 2 Monaten kam es zu keiner Verschlechterung der lokalen Situation, allerdings entwickelte die Patientin eine akute CLL und verstarb.

Zyklus mehrere Lokalrezidive und disseminierte Lungenmetastasen und verstarb an der Grundkrankheit. Zusammenfassung: Unsere Beobachtungen zeigen, dass die Kombinationstherapie mit Cetuximab und Celebrex eine hervorragende Alternative in der Behandlung inoperabler kutaner Plep Ca, insbesondere bei multimorbiden Patienten darstellt.

Literatur: Jalili, A. Methods: The aim of this study was to analyze cutaneous melanoma incidence and Breslow tumor thickness in central Alpine mountain region of South Tyrol, northern Italy.

From Pathology Unit, Bolzano Hospital and South Tyrol Cancer Registry, all newly diagnosed cutaneous in situ and invasive melanomas in the resident population from to were retrieved.

Incidence and Breslow tumor thickness were analyzed. Statistical analyses included Mann-Whitney and Kruskal-Wallis tests.

Results: A total of in situ melanomas and invasive melanomas were collected. Overall European-age standardized melanoma incidence raised from In situ melanomas showed the highest increase from 2.

Invasive melanoma incidence increased from The incidence rise was observed in thin melanomas from 8. Breslow distribution revealed a median value of 0.

Incidence of cutaneous melanoma is increasing in South Tyrol, especially for in situ and thin lesions, but also for thick lesions; no reduction in median tumor thickness is observed.

Probably rural areas and elevated altitudes may contribute to this effect. Derzeit sind 2 Mutationen in diesem Gen im Zusammenhang mit dem Melanom beschrieben: c.

R24C und c. Anamnestisch hat er eine negative Familienanamnese. Die Rolle dieser Transkriptionsfaktoren wurde in anderen Krebserkrankungen wie dem nicht kleinzelligen Lungenkarzinom beschrieben.

Die andere Mutation, c. VL liegt im Exon 4, einer Protein-codierenden Region. Sie wurde bei einer Frau mit einer positiven Familienanamnese Vater sowie einem 0,8mm dickem Melanom, an welchem sie mit dem Lebensjahr erkrankt ist, gefunden.

Beide Regionen wiesen eine hohe Konservierung auf. Only few data are available on the role of mast cells in primary cutaneous T-cell lymphomas CTCL , a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin.

The purpose of this study was to quantify the distribution of mast cells in CTCL variants and clinical stages.

Methods: Immunohistochemistry with a monoclonal anti-mast cell tryptase antibody was performed on formalin-fixed, paraffin-embedded biopsies of 40 patients with different CTCL variants and on control skin samples.

Results: Mast cells were detected in 37 out of 40 cases. In CTCL mast cell density was higher in areas with tumor infiltration than in surrounding dermis.

With the application of image segmentation methods for mast cell quantification on whole-slide digitized sections allowing reproducible and unbiased cell identification, our results strongly implicate a contribution of mast cells to the pathophysiology of CTCL and provide an initial basis for further research on their use as target for therapeutic intervention.

Little data is available on the role of mast cells in primary cutaneous T-cell lymphomas CTCL , a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin.

The aim of the development was to establish a new tissue analysis method on virtual slides for skin sections stained with immunohistochemistry.

The analysis method was designed to set results into a structural context of cell location and of morphological appearance reflecting a certain state of mast cell activation.

Mast cell degranulation was estimated based on the number of connected brown spots for each cell. In addition, an algorithm for the automatic detection of the area of the epidermis was developed, as well as density based CTCL areas.

Furthermore distance between each cell and its closest CTCL area was calculated. Up to mast cells per sample were found in dermis area between 1 and 49mm2.

The presented algorithms provided new data insight of context-based and functional characteristics and could generate surrogate markers for further stratification of CTCL.

In melanoma, the amount of VEGF-C expression, tumour lymphangiogenesis and metastasis to sentinel lymph nodes shows a striking correlation.

Methods: We approached this issue by selecting 22 human melanoma cell lines from primary tumours, skin, lymph node and brain metastasis with a wide spectrum of constitutive VEGF-C production.

We correlated VEGF-C, with expression of target genes of various cell signalling pathways, using the gene expression arrays from these cell lines.

The modulation of the cell signalling pathways was performed with various kinase inhibitors as well as with plasmid constructs.

To substantiate this finding, melanoma cells were treated with various kinase inhibitors targeting components of the MAPK-pathways.

Similar results were obtained when this kinase pathway activity was inhibited with lentiviral shRNA constructs.

Eisendle 1 1 Department of Dermatology, Venereology and Allergology. MAC most often presents as a scar-like papule or plaque on sun-exposed skin and is characterized by aggressive local infiltration, including a high propensity for perineural invasion.

Histologically it might be easily confused with benign adnexal tumours, especially when punch biopsies are performed and first wrong diagnoses of trichoepithelioma, trichoadenoma and syringoma often lead to inappropriate initial treatment.

Tissue invasion by MAC frequently extends far beyond the clinical margins of the tumor recurrence is high. Although metastasis and death from MAC are rare events, significant morbidity can occur as a result of deep local tissue destruction.

Complete surgical removal of the tumour is the treatment of choice. Recent preliminary studies point to higher cure rates with Mohs micrographic surgery.

A year-old healthy female presented with an almost 3 year history of an asymptomatic slowly progressing skin mass on her left eyebrow.

On examination there was a firm nodule measuring 2. Cervical lymphadenopathy was absent. Two deep punch biopsies 4 mm showed a poorly circumscribed, deeply infiltrative tumour with basaloid aspect and perineural invasion confirming MAC.

The patient underwent surgical excision with 1. Histopathology revealed an lateraly and deep incomplete removed tumor R1 infiltrating the muscle bundles with perineural invasion.

A second stage surgery was necessary with lateral and deep enlarging of the defect including the removal of the frontal periostium. Clear histological margins were achieved and the final surgical defect was 6 x 7 cm.

The eyebrow defect was finally reconstructed by a modified AT flap combined with full thickness skin transplantation 56 Poster of the flap dog ears.

The cosmetic outcome was satisfactory, no occurrence was observed after 9 moth follow-up. Conclusion: We confirm the histological difficulties diagnosing this tumour entity and the deep infiltration of MAC.

Removal deep including the periostium might be necessary to completely remove the tumour. They are characterized by aggressive local infiltration but rarely metastasize.

Local recurrence invariably follows inadequate removal. Surgery remains the first-line treatment for both sarcomas and wide surgical excision with a margin between 2 and 4 cm has been recommended.

Mohs Micrographic Surgery has been reported as effective in reducing the rate of local recurrence. Immediate reconstruction with autologous split-thickness skin graft STSG secured by negative wound pressure therapy VAC was performed in all cases.

One case received a porcine xenograft EZ Derm on top of the free Achilles tendon prior autologous split-thickness skin grafting. Application of STSGs instead of flap surgery was performed because it allows immediate closure and fast recognition of local recurrence.

Results: All patients achieved tumor free margins with the first surgical intervention. No local recurrence or distant metastasis occurred Median follow up Functional results were all good and the esthetic outcome was satisfactory.

Because of the lack of excess skin in the areas between the lip and nose, many reconstructions for this area use medial cheek advancement flaps.

Superficial defects of the lateral upper lip may be closed primarily according the skin tension lines and defects closer to the nasolabial fold may be closed primarily within this fold 1.

Case report: In the present article the authors discuss a year-old man who presented to Dermatology Service with a basal cell carcinoma located on the right lateral upper lip.

Tumor size was 12x12 mm; the lesion was excised with security margins determined by polarized light epiluminescence dermoscopy. The final surgical defect size was 15x18 mm.

Results: Although transgressing the facial subunits, eight weeks after surgery, this subcutaneous advancement flap provided a good functional and aesthetic acceptable reconstruction.

The typical presentation is with solitary or few rapidly growing erythematous or bluish plaques or tumors on one leg rarely both legs.

Plaques and tumors may even ulcerate and may be clinically difficult to differentiate from venous leg ulcers.

Methods: We describe for the first time 3 patients with pcDLBCL and an atypical early presentation characterized by macules instead of plaques, tumors or ulcers.

All three patients reported a history of long standing lesions since 6, 9 and 18 months, respectively without a history of rapid enlargement.

Conclusions: pcDLBCL,leg may rarely manifest at presentation with annular erythematous macules instead of plaques or tumors simulating granuloma annulare, necrobiosis lipoidica, sarcoidosis, erythema chronicum migrans, erythema annulare centrifugum or erythema marginatum.

Inoperable Tumoren wurden bislang bestrahlt. Einleitung einer Therapie mit Vismodegib im Februar Allerdings kam es im 5.

Behandlungsmonat zum neuerlichen Tumorwachstum. Bereits nach 1 Monat deutliche Tumorregression, nach 5 Monaten war weder klinisch noch bioptisch Tumorgewebe nachweisbar.

Aim of this study was evaluation of 11 body areas for predicting hirsutism in Kosovar population. Materials and Methods: In this prospective diagnostic study we selected women, with hirsutism and 25 as control group, age years.

Height, weight and a calculation of BMI was obtained. The Ferriman-Gallwey score is used in evaluation of hirsutism. The examiner scored the subjects on a scale of for terminal hair growth on eleven different body areas according to the Ferriman-Gallwey FG scoring system.

An FG score of 8 or more was considered diagnostic of hirsutism. A thorough physical examination with specific emphasis on signs of virilization including frontal baldness, loss of female body contours, increased muscularity, acne, clitoromegaly, and atrophy of breast was done in all patients.

Results: The age group with highest scoring were women under 20 years and age group years on average value The range of average scoring in different parts of the body was: 3.

Conclusion: The FG scoring system was found to be clinically useful. The feet, thighs, arms and chin were observed to have the highest score of androgen sensitive area of the body.

The FG scoring system has great significance and value to establish the diagnosis of hirsutism and is an acceptable screening method.

Key words: hirsutism, evaluation, Ferriman-Gallwey score. In prior studies, the most common treatment emergent neuropsychiatric adverse events for ATR included abnormal dreams and dizziness.

W96 safety and efficacy were secondary endpoints presented here. Conclusion: EPA demonstrated non-inferior efficacy and a favorable safety profile versus ATR with fewer discontinuations due to adverse events and fewer neuropsychiatric adverse events including abnormal dreams and dizziness.

We report the safety and tolerability profiles of STB vs comparators through W Methods: We report results from prospective, randomized, open-label, Phase 3b trials of regimen switching to STB.

STB was safe and well-tolerated with similar rates of AEs. Liu 10, David Piontkowsky 10, Martin S. Similar to ritonavir, cobicistat inhibits renal creatinine secretion, leading to a small increase in serum creatinine, without affecting the actual GFR.

Results: Rates of renal discontinuations were STB 1. Of those, 0. All PRT cases improved after study drug discontinuation.

Tubular abnormalities were similar between treatment groups regardless of baseline eCrCL. Insgesamt wurden Patienten getestet, an der Klinik und im niedergelassenen Bereich.

Eine Aufnahme dieser Erkrankungen in eine nationale Leitlinie ist anzustreben. Capecitabine as well as the widely used blood pressure regulating angiotensin converting enzyme inhibitors ACEIs are prone to cause severe coutaneous side effects.

In the present study, we sought to evaluate the potential influence of ACEIs on the appearance and severity of capecitabine-induced HFSR in breast cancer patients.

Patients who received chemotherapy bevacizumab and capecitabine and treatment with ACEIs were evaluated for incidence and intensity of capecitabine-induced HFSR.

Results: HFSR was observed in In South Tyrol a threepart triage system to gain faster treatment for urgent and emergent cases of dermatology outpatients has been introduced by the Provincial Government.

The defined threepart triage levels are urgent, priority and deferrable with a corresponding maximum time target before treatment of 1, 8 and 60 days respectively.

Methods: from February to August a sample of outpatient electronic medical records cases were randomly retrieved. Referral diagnoses with their corresponding triage codes were recorded.

Urgent visits were further analyzed according to the referring physician. The appropriateness of the referral was determined on the basis of the published state law diagnostic guidelines.

Data were statistically analyzed using the 2-tailed Pearson Chi2 test or the Fisher exact test. Results: Overall, Conclusion: The triage system according to clinical need is safe, no urgent cases are overseen.

Frequency of diagnoses differ significantly in the three triage levels, this in general points to an operating allocation system.

In the north Italian province of South Tyrol waiting times for non urgent dermatological specialist referrals and requests for specialist care are monitored centrally by the local government.

Methods: We performed a retrospective study regarding the correlation between monthly waiting time and number of access requests for the city of Bolzano, where the basin comprises approximately The monitored time included data from November to July provided by the central monitoring agency.

Results: The results of the analysis showed that the median waiting time for a non urgent dermatology referral was 57 days in the first year of the monitoring and was slowly increasing: it was 30 days at the begin of the year and 61 days at the end of the year.

Due to staff shortage waiting time increased sharply at the end of until reaching a maximum of days in January With the allocation of new physicians, waiting time then decreased to 49 days in July Not surprisingly waiting time correlates strongly negative with requests for access in specialist health care.

Allocation of adequate human resources reduces waiting time, but augments requests for specialist consultations. Anamnestisch starker Nicotinabusus.

Neben einer Psoriasis vulgaris wird auch die Verdachtsdiagnose eines Bazex-Syndrom gestellt und eine Tumor-Suche begonnen.

Epicutantest und Pilzkultur blieben ebenfalls ohne Ergebnis. Diskussion: Die Acrokeratosis paraneoplastica Bazex ist eine sehr seltene, obligate Paraneoplasie und tritt vor allem im Zusammenhang mit Plattenepithelkarzinomen des aerodigestiven Traktes auf; in der Literatur findet sich jedoch auch ein Auftreten bei anderen Neoplasien, z.

Beschrieben wurde das Bazex-Syndrom bisher v. Die typische Klinik umfasst schuppende, unscharf begrenzte, symmetrische, psoriasoforme Erytheme an den Akren sowie distale Hyperkeratosen und Rhagaden.

Weiters sind typisch eine Onychodystrophie, sowie Hyperkeratosen an den Ohren, und evt. LE-artige Gesichts-Erytheme. Als Differentialdiagnosen kommt neben einem Ekzem vor allem eine Psoriasis palmoplantaris vom keratotischen Typ in Frage.

Die Pathogenese ist weitgehend unbekannt. Die Therapie liegt in erster Linie in einer Malignomsanierung. Bull Soc Franc Derm Syph, Acrokeratosis paraneoplastica Bazex syndrome.

JEADV, Therefore, we studied the expression and localization of those and other inflammation and fibrosis markers in scarring and non scarring skin of RDEB patients and healthy donors by sqRT-PCR, immuno blots, and IF microscopy.

Conclusion: Our results point to an important role of inflammation and fibrosis in impaired wound healing, finger contractures and pseudosyndactyly in RDEB.

The role of myofibroblasts is unclear. This study revealed potential therapeutical targets to improve wound healing and finger contractures in RDEB.

Reportedly, topical antibiotics, corticosteroids and calcineurin inhibitors only have temporary efficacy.

Patients and methods: Four male patients with a history of surgical and conservative topical treatment for in situ squamous cell carcinomas of the scalp, were admitted because of recurrent pustular flares, erosions and crusts restricted to the bald scalp, recalcitrant to multiple topical therapies.

Direct immunofluorescence was negative in all. Results: After initial improvement all pts developed recurrences under consecutive dapsone therapy, thus it was discontinued after four weeks.

In contrast, subsequent treatment with a topical classsteroid mometasonfuroat induced complete remissions within weeks, but all pts developed relapses following cessation of therapy.

Nevertheless, all recurrences could rapidly be managed by reintroduction of this regimen, moreover, further relapses were completely prevented by intermittent application of mometasonfuroat times per week.

Conclusion: Here we show that topical treatment with dapsone-gel was not effective in our pts. Dramatic improvement was achieved with a topical classsteroid, but long term remissions required continuous, intermittent therapy, which underscores the recalcitrant nature of the disease.

Since surgical treatment in one pt led to a long lasting disease free period, this approach may represent an interesting alternative in severe cases.

Pathogenesis is poorly understood and the clinical course of PG is impredictable. The disease might regress spontaneously, stay inactive for months or progress and worsen after trauma, surgical interventions or even without triggers.

No gold standard has been established for the treatment of PG. The role of surgical interventions and Negative Wound Pressure Therapy NWPT is controversially discussed in the literature as these procedures might pose a trigger to further aggravate the condition.

Material and methods: We report 10 consecutive patients affected by PG, three males and six women median age 65, range from 26 - The extremely painful ulcers were all situated on the lower extremities, except of one case of post augmentation mastopexy pyoderma and measured from 8 x 4 cm to 45 x 25 cm.

All patients were hospitalized prior to surgical intervention and received methylprednisolone and in most cases further immunosuppressive or immunomodulatory therapy including dapsone, ciclosporine, infliximab, methotrexate or pentoxyphylline.

NWPT was applied up to one week prior further surgical interventions. Gentle surgical debridement of the wound bed and wound borders was performed in local tumescence anesthesia and 0,3 mm thickness skin grafts STSG were transferred and secured by NWPT.

One case was not grafted because it showed fast intrinsic healing with good epithelialization under NWPT and the mammary case was grafted without applying NWPT.

All cases of PG did markedly improve with the application of NWPT, as with the surgical intervention, no case of pathergy was observed, neither from application of NWPT nor from skin grafting.

Discussion: This is the largest case series of surgical treatment for PG reported in the literature. Blister formation can also be induced via autoimmune reactions directed against self antigens as known for bullous pemphigoid.

In either case the structural integrity of the integument is affected, which leads to blistering. The primary genetic causes of epidermolyis bullosa may induce secondary effects that aggravate the disease phenotype by activating the expression of factors that degrade extra-cellular matrix components and thereby further weaken the structural integrity of the skin.

Methods: We analysed the gene expression profiles of patient derived EB-simplex Dowling-Meara cell lines in vitro as well as the composition of blister fluids of different EB subtypes in vivo.

Results: Gene expression profiles of EB-simplex Dowling-Meara cell lines revealed increased expression of matrix metalloproteinase-9 and interleukin We identified high levels of these two factors in all blister fluid samples compared to healthy controls.

Due to the fact that these two factors are causally responsible for blister formation, and that they are also expressed in high levels in epidermolysis bullosa skin, they constitute potential therapeutic targets for small molecule based therapies.

Nevertheless, they both exhibit increased plasma IgE and numbers of mast cells in the upper dermis, indicating an atopic predisposition.

Women with PCOS may have enlarged ovaries that contain small collections of fluid -called follicles -located in each ovary as seen during an ultrasound exam.

Infrequent or prolonged menstrual periods, excess hair growth, acne, and obesity can all occur in women with polycystic ovary syndrome.

It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome PCOS should be evaluated for the metabolic syndrome.

We present the case of 24 year old female patient with hirsutism. She was underweight, had acne and positive family history for hirsutism and diabetes.

She was evaluated to identify etiology, and was diagnosed as a case of PCOS with insulin resistance. It is very rare case when PCOS women with insulin resistance is underweight.

She was treated according to underlying pathology and improvement was significant after 6 month. Etablierte Therapien der GM umfassen Methotrexat ev.

Die Evaluierungen erfolgten vor Therapiebeginn Baseline sowie unmittelbar und sechs Monate nach Therapieabschluss. Ergebnis: Unmittelbar nach der Therapie war der Bewegungsumfang nahezu aller Gelenke verbessert.

Die Handkraft hingegen nahm weiter zu li. Weiters konnte ein nachhaltiger Effekt bis 6 Monate nach Therapieende beobachtet werden.

Sie sind zumeist durch hohe Temperaturen gekennzeichnet. Differentialdiagnostisch wurden Diabetes mellitus, eine Venenthrombose, eine Uveitis sowie ein Irvine-Gass-Syndrom ausgeschlossen.

Dies unter anderem durch die Inhibition von NK-kB. Prevalence of age-related macular degeneration in the United States.

Arch Ophthalmol. Br J Dermatol. Dimethylfumarate is a potent inducer of apoptosis in human T cells. J Invest Dermatol.

J Immunol. Suppression of VEGFR2 expression in human endothelial cells by dimethylfumarate treatment: evidence for anti-angiogenic action.

Fumarate esters as angiogenesis inhibitors: key to action in psoriasis? Leonardi C et al. Louis University School of Medicine, St.

LY Greater clinical response is associated with improved patient reported outcomes: results from a phase 2 study in patients with moderate to severe psoriasis treated with ixekizumab.

The pathogenesis of Schnitzler-Syndrom is currently under investigation and is supposed to be related to excessive interleukin-1, which is further evidenced by the good and rapid clinical response to ILblockade.

Methods: A year old female patient suffered from intermittent urticaria combined with fever and strong arthralgia as well as increased levels of CRP since Over the years a lot of diagnostic investigations were done without concrete findings, and therapuetic attempts with anti-histamines and classical immunosuppressants failed.

The decision to start monotherapy with interleukin-1 receptor antagonist anakinra; mg subcutaneously every 24 hours was made in October At that time the patient had severe symptoms and histology revealed a leukocytoclastic vasculitis, compatible with urticaria-vasculitis for the first time.

After starting anakinra, symptoms disappeared within 24 hours. An interruption of therapy in November resulted in a rapid return of symptoms.

These suggested the diagnosis of Schnitzler-Syndrom. Today, 5 months after starting continuous therapy with anakinra, the patient is free of symptoms and beside mild dermatitis at the injection site no adverse drug effects have been registered.

Results: Monotherapy with the interleukin-1 receptor antagonist anakinra is a highly effective therapeutic option in Schnitzler-Syndrom.

Other IL-1 inhibiting agents, such as rilonacept, are currently under investigation. Rezente Erkenntnisse zeigen uns, dass Psoriasis eine Systemerkrankung ist.

Seit ca. Zagreb do Kassel. Zagreb do Venecija - Mestre. Zagreb do Luzern. Zagreb do Nurtingen. Zagreb do Matulji. Zagreb do Ugljan.

Zagreb do Jadranovo. Zagreb do Osor. Zagreb do Drage. Zagreb do Trst Opicina. Zagreb do Baderna. Zagreb do Soblinec. Zagreb do Kotorsko.

Na usputnim stanicama se jako zurio i za toa Vecina stvari a veliki plus je kaj smo stigli 10 min ranije. Bravo vozaci.

Zagreb do Oskarshamn Oskarshamn do Zagreb. Najbolja ponuda Najbolja ponuda. Zagreb Kliknite ovdje za otvaranje lokacije na Google karti.