Gutenberg war gestern: Ein Beitrag zur Ausbildung in der Medizin gestern, heute und morgen

Zusammenfassung: Eine gute Ausbildung ist die wichtigste Grundlage einer zuverlässigen medizinischen Versorgung und des medizinischen Fortschritts. Unser medizinisches Wissen hat in den vergangenen 50Jahren stärker zugenommen als in den 500Jahren zuvor. Die räumlichen und personellen Kapazitäten unserer Hochschulen sind bei den bestehenden Unterrichtsstrukturen überfordert. Ein Teil der Probleme lässt sich durch "Blended Learning" lösen, d.h. einer Kombination aus klassischen Unterrichtsmethoden (Frontalvorlesungen, Kurse, bettnaher Unterricht) mit ergänzendem webbasiertem E-Learning. Neben einem soliden Grundwissen muss heute auch die Fähigkeit vermittelt werden, mit modernen Medien umzugehen und sich auf ein lebenslanges Lernen vorzubereiten. Aus der großen Zahl von E-Learning-Angeboten sollen hier stellvertretend für eine studentische Ausbildungsplattform das Programm DOIT (Dermatology Online with Interactive Technology; http://www.swisdom.org) sowie das Programm Dermokrates (http://www.Dermokrates.com) der Deutschen, Österreichischen und Schweizerischen Dermatologischen Gesellschaften für die ärztliche Weiter- und Fortbildung genannt werden. Das größte Hindernis bei der Umsetzung neuer Entwicklungen liegt im Festhalten an überkommenen Strukture

Disfiguring Annular Sarcoidosis Improved by Adalimumab

Depending on the location, dermatoses can produce blemishes that severely impair quality of life and require highly effective treatment that is otherwise used for extensive skin involvement. We report the case of a 39-year-old, otherwise healthy male disfigured by an 8 × 7-cm hypopigmented and centrally atrophic annular plaque with erythematous indurated borders in an area of scar tissue on his forehead. Skin biopsies revealed non-caseating granulomas, and hilar involvement was identified, leading to the diagnosis of systemic sarcoidosis stage II with cutaneous involvement. The lesions proved resistant to multiple therapies, but responded within 4 months to adalimumab with regression of the lesion and inflammatory infiltrate. The visual analogue scale of disease activity decreased from 7/10 to 3.5/10, and the Dermatology Life Quality Index from 16/30 to 3/30 points. In conclusion, TNF-α inhibition can control inflammation and disfigurement by cutaneous sarcoidosis and restore quality of life

Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring.

The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses

Retrospective analysis of alpha‐human papillomavirus (HPV) types in tissue samples from anogenital dysplasias – introduction of the RICH (Risk of HPV‐related Carcinoma in HIV+/− patients) score

Background Chronic viral infections caused by highly contagious human papillomaviruses (HPVs) from the alpha genus are a substantial risk factor for tumour diseases. Objectives The goal of this study was to compare the HPV infection pattern with histology in a patient group of immunocompromised HIV+ and non‐immunocompromised patients with anal intraepithelial neoplasia. Materials and Methods Tissue samples (n = 210) from the anogenital area of 121 patients underwent retrospective histological and molecular examination for HPV DNA prevalence by chip analysis. The study was part of a cancer screening from the Dermatology Department of the LMU Munich, Germany. All data were collected and processed anonymously. Results HPV 6 or 11 are more abundant in tissue samples from histologically diagnosed condylomata acuminata (47.7%) compared to grade 1, 2, and 3 intraepithelial neoplasias (IN 1‐3). Detection of high‐risk (hr) alpha‐HPV DNA was significantly higher in tissue samples from IN 3 (67.5%) compared to IN 1 and 2 (12.9%), and compared to condylomata acuminata (29.5%). No HPV types were detected in histologically unremarkable tissue samples. There was a significant association between the prevalence of HPV 16 and the classifications IN 1 to IN 3 (χ2 (2) = 13.62, P = 0.001). We identified a significant correlation between the prevalence of high‐risk and low‐risk (lr) HPV types and HIV, especially mixed infections of different HPV types correlated with high‐grade IN. Based on the present data, we suggest the risk of carcinoma in HIV+/− patients (RICH) score and test it in the 121 patients. Conclusions hr alpha‐HPVs, mainly HPV 16, are associated with increased oncogenic potential of premalignant lesions (IN 1‐3), especially in HIV+ patients. Based on the combination of HIV/HPV‐testing and histological analysis, we identified correlations that could potentially forecast the risk of malignant transformation and summarized them in the form of RICH score

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)

The severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens-Johnson syndrome is characterized by epidermal loss due to massive keratinocyte apoptosis and/or necroptosis. EN is often caused by a drug mediating a specific TCR-HLA interaction via the (pro)hapten, pharmacological interaction or altered peptide loading mechanism involving a self-peptide presented by keratinocytes. (Memory) CD8 + T cells are activated and exhibit cytotoxicity against keratinocytes via the perforin/granzyme B and granulysin pathway and Fas/FasL interaction. Alternatively drug-induced annexin release by CD14 + monocytes can induce formyl peptide receptor 1 death of keratinocytes by necroptosis. Subsequent keratinocyte death stimulates local inflammation, activating other immune cells producing pro-inflammatory molecules and downregulating regulatory T cells. Widespread epidermal necrolysis and inflammation can induce life-threatening systemic effects, leading to high mortality rates. Research into genetic susceptibility aims to identify risk factors for eventual prevention of EN. Specific HLA class I alleles show the strongest association with EN, but risk variants have also been identified in genes involved in drug metabolism, cellular drug uptake, peptide presentation and function of CD8 + T cells and other immune cells involved in cytotoxic responses. After the acute phase of EN, long-term symptoms can remain or arise mainly affecting the skin and eyes. Mucosal sequelae are characterized by occlusions and strictures due to adherence of denuded surfaces and fibrosis following mucosal inflammation. In addition, systemic pathology can cause acute and chronic hepatic and renal symptoms. EN has a large psychological impact and strongly affects health-related quality of life among EN survivors.Dermatology-oncolog

Evaluation of the Interplay between the ADAR Editome and Immunotherapy in Melanoma.

RNA editing is a highly conserved posttranscriptional mechanism that contributes to transcriptome diversity. In mammals, it includes nucleobase deaminations that convert cytidine (C) into uridine (U) and adenosine (A) into inosine (I). Evidence from cancer studies indicates that RNA-editing enzymes promote certain mechanisms of tumorigenesis. On the other hand, recoding editing in mRNA can generate mutations in proteins that can participate in the Major Histocompatibility Complex (MHC) ligandome and can therefore be recognized by the adaptive immune system. Anti-cancer treatment based on the administration of immune checkpoint inhibitors enhance these natural anti-cancer immune responses. Based on RNA-Seq datasets, we evaluated the editome of melanoma cell lines generated from patients pre- and post-immunotherapy with immune checkpoint inhibitors. Our results reveal a differential editing in Arthrobacter luteus (Alu) sequences between samples pre-therapy and relapses during therapy with immune checkpoint inhibitors. These data pave the way towards the development of new diagnostics and therapies targeted to editing that could help in preventing relapses during immunotherapies

Inhibition of death receptor signals by cellular FLIP.

The widely expressed protein Fas is a member of the tumour necrosis factor receptor family which can trigger apoptosis. However, Fas surface expression does not necessarily render cells susceptible to Fas ligand-induced death signals, indicating that inhibitors of the apoptosis-signalling pathway must exist. Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues. The short form, FLIPs, contains two death effector domains and is structurally related to the viral FLIP inhibitors of apoptosis, whereas the long form, FLIP(L), contains in addition a caspase-like domain in which the active-centre cysteine residue is substituted by a tyrosine residue. FLIPs and FLIP(L) interact with the adaptor protein FADD and the protease FLICE, and potently inhibit apoptosis induced by all known human death receptors. FLIP(L) is expressed during the early stage of T-cell activation, but disappears when T cells become susceptible to Fas ligand-mediated apoptosis. High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis