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# Neue Studie: Autoimmunerkrankungen und Herzrhythmusstörungen **Forscher der Universität Gießen haben untersucht, ob Autoimmunerkrankungen das Risiko für Vorhofflimmern erhöhen.**[2] Diese Studie basiert auf echten Patientendaten von deutschen Arztpraxen. Das ist wichtig für dich zu wissen: Menschen mit Autoimmunerkrankungen wie Psoriasis-Arthritis leben mit einer überaktiven Körperabwehr. Diese dauerhafte Entzündung kann nicht nur die Gelenke treffen, sondern auch das Herz beeinflussen. Vorhofflimmern ist eine Herzrhythmusstörung, bei der das Herz unregelmäßig schlägt.[4] Das erhöht die Schlaganfallgefahr. Andere Studien zeigen bereits: Patienten mit rheumatoider Arthritis haben ein etwa 1,5-fach höheres Risiko für Vorhofflimmern.[3] Die neue deutsche Studie schaut sich an, wie häufig diese Verbindung in der Praxis vorkommt und ob Männer und Frauen unterschiedlich betroffen sind.[2] Solche Erkenntnisse helfen Ärzte dabei, Menschen mit Autoimmunerkrankungen besser zu überwachen. Falls du mit Psoriasis-Arthritis lebst, ist es sinnvoll, dein Herz regelmäßig kontrollieren zu lassen. Das solltest du mit deinem Arzt besprechen. Originaltitel: Association between autoimmune diseases and atrial fibrillation: a real-world analysis from German outpatient data. Link zur Quelle

Originaltitel: Northwestern European Ancestry Predominates in Idiopathic Subglottic Stenosis: Results From an English-Speaking Cohort. Link zur Quelle

Originaltitel: The IL-36 cytokine family: From barrier immunity to therapeutic target in inflammatory diseases. Link zur Quelle

Originaltitel: Oncostatin M upregulates CD73 via the MAPK pathway in keratinocytes to promote an adenosine-dependent anti-inflammatory response in psoriasis. Link zur Quelle

Originaltitel: Air Pollution and Skin Diseases: A Systematic Review of Epidemiological Evidence. Link zur Quelle

Trial number: 2023-507415-35-00 Overall trial status: Ongoing, recruitment ended Trial title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Safety of Tildrakizumab in Anti-TNF Experienced Subjects with Active Psoriatic Arthritis I (INSPIRE 1) Medical conditions: Psoriatic Arthritis Status in each country: Czechia:Ended, Germany:Ended, Estonia:Ended, Spain:Ended, Slovakia:Ongoing, recruitment ended, Italy:Ended, Poland:Ended Trial phase: Therapeutic confirmatory (Phase III) Therapeutic Areas: Diseases [C] - Skin and Connective Tissue Diseases [C17] Primary end point: The proportion of subjects who achieve ACR20 at Week 24 Secondary end point: N/A Age of participants: 18-64 years, 65+ years Gender of participants: Female, Male Trial region: In both EEA and non-EEA Planned number of participants: 204 Sponsor: Sun Pharmaceutical Industries Limited Sponsor type: Pharmaceutical company Trial product: Ilumetri 100 mg solution for injection in pre-filled syringe, tildrakizumab placebo solution for injection in pre-filled syringe Results posted: No Overall decision date: 31/05/2024 Countries decision date: PL: 21/06/2024, ES: 04/06/2024, IT: 01/07/2024, DE: 31/05/2024, CZ: 04/06/2024, SK: 31/05/2024, EE: 31/05/2024 Last updated date: 10/04/2025Den kompletten Artikel zeigen

No abstract supplied.Weiterlesen

No abstract supplied.Weiterlesen

# Biologika gegen Schuppenflechte: Auch bei Krebs sicher? Die neue Studie untersucht ein wichtiges Thema. Es geht darum, ob Biologika gegen Schuppenflechte gefährlich sind, wenn du gleichzeitig Krebs hast oder hattest. Das ist für viele Patienten eine große Sorge. Die gute Nachricht zuerst: **Biologika scheinen sicher zu sein**[1][5]. Ärzte können sie auch bei aktiven oder kürzlich diagnostizierten Krebserkrankungen einsetzen. Du musst deine Schuppenflechte also nicht leiden lassen, nur weil du Krebs hast. Allerdings gibt es Unterschiede zwischen den verschiedenen Biologika. **TNF-α-Hemmer** erhöhen das Krebsrisiko leicht[2]. Besonders das Lymphom-Risiko steigt. **IL-12/23-Hemmer** und **IL-17-Hemmer** sind dagegen besser[2][3]. Sie senken sogar das Gesamtkrebsrisiko oder beeinflussen es gar nicht. Experten empfehlen daher: Wenn du Krebs hast, wählt dein Arzt eher IL-17 oder IL-23-Hemmer[3]. Die Behandlung wird sehr individuell geplant. Es zählt deine ganze Situation. Das Wichtigste ist offene Kommunikation zwischen dir, deinem Hautarzt und deinem Onkologen. Gemeinsam findet ihr die beste Lösung für dich. Originaltitel: Comment on "Cancer progression, recurrence, and infection outcomes in psoriasis patients with active or recent malignancy treated with biologic therapy". Link zur Quelle

BackgroundPsoriasis is frequently accompanied by depression. However, the role of specific symptom domains, including cognitive-affective and somatic symptoms, as well as potential metabolic mediators between psoriasis and depression, remains unclear.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES, n = 14,964) and the Health and Retirement Study (HRS, n = 4364). Depressive symptoms were classified into cognitive-affective and somatic domains. Cross-sectional associations were evaluated in NHANES, and longitudinal symptom trajectories were identified in HRS using group-based trajectory modeling. Based on genome-wide association study summary statistics, bidirectional and two-step Mendelian randomization (MR) were performed to assess causality and identify plasma metabolite mediators.ResultsIn NHANES, total depressive symptoms (OR = 1.03, 95% CI: 1.01-1.06, P = 0.018) and somatic symptoms (OR = 1.08, 95% CI: 1.03-1.12, P = 0.003) showed positive associations with psoriasis, but not cognitive-affective symptoms. In HRS, persistently high trajectories of total (OR = 1.58, 95% CI: 1.08-2.32, P = 0.018) was associated with psoriasis, with no significant association for the cognitive-affective and somatic domains after full adjustment. MR supported a causal relationship of psoriasis on depression and identified sphingomyelin (d17:2/16:0, d18:2/15:0) and urate as mediators, accounting for 10.2% and 6.8% of the total effect, respectively.ConclusionDepressive symptoms were linked to psoriasis in both cross-sectional and longitudinal analyses. Lipid and antioxidant-related pathways involving sphingomyelin and urate may mediate the relationship between psoriasis and depression, offering potential targets for intervention.Weiterlesen

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BackgroundPsoriasis, a chronic autoimmune condition, can severely impact patients' well-being. It is characterized by erythema, thickening, and scaling of the skin. Plaque psoriasis, the most prevalent type, affects 80%-90% of psoriasis patients, ranging from localized to severe cases. Although corticosteroids are commonly used to treat psoriasis, prolonged use poses risks. Therefore, alternative therapies are needed. Roflumilast, a potent phosphodiesterase 4 inhibitor, is currently being considered as a treatment for plaque psoriasis.MethodsWe searched four electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Scopus, and Web of Science) up to March 2024 for relevant articles evaluating the efficacy and tolerability of roflumilast in the management of psoriasis. The quality of evidence from trials was assessed using the Cochrane Risk of Bias tool (RoB1). Data from the included studies were extracted into a standardized online sheet and analyzed using RevMan 5.4.ResultsRoflumilast significantly increased the proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 and a 2-point improvement score at both weeks 4 and 8 compared to placebo (RR = 3.48, 95% CI [2.04 to 5.92], P < 0.00001, and RR = 4.02, 95% CI [3.17 to 5.11], P < 0.00001, respectively). The pooled studies demonstrated homogeneity at both weeks 4 (P = 0.17, I² = 38%) and 8 (P = 0.38, I² = 5%). Regarding the results of the Psoriasis Area and Severity Index, 75% favored roflumilast over placebo (RR = 2.72, 95% CI [1.18 to 6.28], P < 0.00001, and RR = 3.41, 95% CI [2.19 to 5.32], P < 0.00001, at weeks 4 and 8, respectively). Subgroup analysis addressed the observed heterogeneity in the results.ConclusionThis meta-analysis represents the first investigation into the efficacy and safety of roflumilast for treating psoriasis. Results suggest that roflumilast is both effective and well-tolerated in managing psoriasis. However, additional robust clinical trials are needed to validate these observations..Weiterlesen

Interleukin-23 (IL-23) inhibitors represent a major advance in the management of moderate-to-severe plaque psoriasis, grounded in the central pathogenic role of the IL-23/Th17 axis. By selectively targeting the p19 subunit, guselkumab, risankizumab, and tildrakizumab effectively suppress disease-driving inflammation while preserving IL-12-mediated host defence. Pivotal randomized trials have demonstrated high levels of skin clearance, durable efficacy, and favourable safety profiles. Nevertheless, such trials only partially reflect the heterogeneous and medically complex populations treated in everyday practice. Against this background, this narrative review focuses on the expanding body of real-world evidence, which has provided novel insights into the long-term durability, drug survival, performance in difficult-to-treat anatomical sites, and safety of IL-23 inhibitors in special and comorbid populations. Real-world studies consistently confirm high effectiveness in elderly patients, individuals with multiple comorbidities, and those with extensive prior biologic exposure, as well as in challenging disease localisations such as scalp, nails, palmoplantar, genital, and pretibial psoriasis. Across large observational cohorts, IL-23 inhibitors show excellent treatment persistence, largely driven by sustained efficacy and low rates of discontinuation for adverse events. Reassuring safety profiles have also been documented in patients with a history of malignancy, latent infections, or cardiometabolic disease, together with improvements in quality of life and systemic inflammatory burden. By integrating evidence from randomized trials with large real-world cohorts, this narrative review provides a clinically oriented synthesis of the efficacy, safety, and therapeutic positioning of IL-23 inhibitors in psoriasis. Although all three agents demonstrate high and durable effectiveness, real-world data suggest subtle intraclass differences, with guselkumab and risankizumab often achieving faster or deeper early responses, and tildrakizumab offering greater dosing flexibility with comparable long-term persistence in selected patient profiles. Overall, IL-23 blockade has evolved from a highly effective trial-based strategy into a versatile and reliable long-term therapeutic approach capable of addressing unmet needs in routine clinical practice.Weiterlesen

IntroductionPsoriasis is a chronic inflammatory skin disease associated with significant physical and psychological burden. Tildrakizumab, an interleukin-23 p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe plaque psoriasis both in clinical trials and real-world setting. However, limited data are available on the impact of the effective treatment of psoriasis on the psychological health of patients. The aim of this study was to assess changes in psychological well-being, as well as clinical and quality-of-life outcomes, in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in routine clinical practice in Italy.MethodsThis was an interim analysis (IA) of a 52-week multicenter, prospective, observational study. Adults with moderate-to-severe plaque psoriasis initiating tildrakizumab were enrolled. Endpoints focused on well-being and psychological health and included changes, from baseline to week 28, in Depression, Anxiety, and Stress Scale-21 (DASS-21) scores, Dermatology Life Quality Index (DLQI), European Social Survey (ESS) items, and World Health Organization-Five Well-Being Index (WHO-5). Effectiveness was also monitored via Psoriasis Area and Severity Index (PASI), and safety via treatment-emergent adverse event reporting.ResultsA total of 115 patients were included (mean age 52.5 years, 60.8% male), 102 receiving ≥ 1 dose of tildrakizumab and completing DASS-21 evaluations at baseline and week 28. At week 28, improvements were observed in DASS-21 subscales [depression (- 2.6, 95% CI - 2.0 to - 1.0), anxiety (- 2.3, 95% CI - 2.0 to - 1.0), and stress (- 3.4, 95% CI - 4.0 to - 2.0)], accompanied by marked PASI reduction (- 13.7, 95% CI - 12.8 to - 10.1). DLQI, ESS, and WHO-5 scores also improved. Adverse events were generally mild or moderate, with no unexpected safety signals.ConclusionIn this real-world IA, tildrakizumab was observed to improve the psychological well-being of patients, reflected by a reduction in all items of the DASS-21 scale and, in parallel, confirmed its effectiveness in managing physical symptoms of psoriasis, establishing its role in the holistic management of psoriasis.Weiterlesen

Abstract Objective To explore the clinical application value of Neutrophil extracellular traps (NETs) in evaluating psoriasis. Methods 2ml peripheral blood of 63 patients with psoriasis and 27 healthy controls were collected. Neutrophils were isolated by density gradient method, and the formation of NETs was observed by immunofluorescence staining. We then calculated the proportion and fluorescence intensity of NETs and analyzed their correlation with clinical classification, severity, and serological indicators. Furthermore, the skin lesions of 5 patients with psoriasis were collected, and the NETs were observed by immunofluorescence method. Results The proportion and fluorescence intensity of spontaneous NETs in patients with psoriasis were significantly higher than those in healthy controls and were positively correlated with the PASI scores. The generation of NETs in psoriasis patients with metabolic syndrome (MetS) or high-TNF-α was higher than in psoriasis patients without metabolic abnormalities or normal-TNF-α. NETs were also observed in most psoriatic skin specimens. Conclusions The levels of NETs are correlated with the disease severity of psoriasis and patients with metabolic abnormalities and may be used as a clinical indicator to reflect the inflammatory state of psoriasis and metabolic comorbidity of psoriasis for disease evaluation. Weiterlesen

Psoriasis is a chronic, relapsing inflammatory skin disease. Topical treatments are the primary choice for up to 80% of psoriasis patients; however, their effectiveness is often limited by poor penetration into the skin. Nanocarriers represent a promising advancement in drug delivery systems by enhancing bioavailability and tissue penetration and reducing the frequency of dosing. This study conducted a narrative review and analyzed the characteristics of clinical trials registered on ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) that investigated the use of nanocarriers for psoriasis treatment. The findings indicate that the proportion of registered randomized controlled trials (RCTs) focusing on nanocarriers for psoriasis treatment is exceedingly limited, comprising only 0.2% (11 out of 5338) of all registered RCTs related to psoriasis treatment. Among these 11 RCTs, six types of nanocarriers were identified: microemulsion/nanoemulsion, chitosan nanoparticles, liposomes, ethosomes, micelles, and niosomes. Five trials reported complete or partial outcomes using the Psoriasis Area and Severity Index (PASI) as the primary efficacy measure. However, many trials had incomplete baseline and follow-up PASI data. Studies have shown that encapsulating APIs within nanocarriers generally yields a more significant reduction in PASI scores than administering empty nanocarriers. Additionally, no study has directly compared nanocarriers with traditional formulations. The APIs used in these RCTs primarily comprised lipophilic drugs. In conclusion, although nanocarriers for psoriasis treatment demonstrate significant potential, they continue to face challenges, including incomplete regulatory frameworks, difficulties in large-scale production, and high production costs.Weiterlesen

Abstract Background This study collected and analyzed clinical data from patients with psoriasis, developing and validating a risk prediction model for psoriasis relapse. The aim is to improve the efficiency and accuracy of early screening for psoriasis relapse in clinical practice and to provide a reference for implementing preventive measures. Objective To develop and validate a risk prediction model for psoriasis relapse. Methods A convenience sampling method was used to select 504 psoriasis patients admitted to a tertiary hospital in China between January 2022 and December 2024, including 353 cases in the training set and 151 cases in the test set. Independent risk factors for psoriasis relapse were identified through univariate analysis and logistic regression analysis to develop a prediction model. A nomogram and SHAP summary plot were generated for model visualization, and the model’s goodness of fit and discriminative ability were evaluated. Results The one-year relapse rate of psoriasis patients after treatment was 66.67%. Logistic regression analysis identified body mass index (BMI), diabetes, biologic agent use, smoking, upper respiratory tract infection (URTI), and non-standard medication as independent risk factors for psoriasis relapse, which were included in the model. The area under the ROC curve (AUC) values for the training and testing sets were 0.767 [95% CI: 0.715–0.818] and 0.704 [95% CI: 0.620–0.789], respectively. The model demonstrated good discrimination and calibration, and decision curve analysis (DCA) showed significant net benefit in both the training and testing sets. Conclusion The psoriasis relapse risk prediction model developed in this study demonstrated good predictive performance. This model can serve as an effective reference for assessing the risk of psoriasis relapse and provides valuable insights for developing personalized prevention strategies for patients. Weiterlesen

No abstract supplied.Weiterlesen

IntroductionInterleukin-17 inhibitors (IL-17i) and interleukin-23 inhibitors (IL-23i) are advanced therapeutic options for moderate-to-severe psoriasis. In real-world settings, biologic persistence is commonly used as a proxy for effectiveness and safety, and a treatment-free status following biologic discontinuation may provide insights into disease remission. This study aimed to assess persistence and treatment-free status for IL-17i versus IL-23i among biologic-naïve patients with psoriasis in Japan.Patients and methodsThis retrospective cohort study analyzed data from the Japanese Medical Data Vision database from 01 January 2015 to 31 December 2022. Patients diagnosed with psoriasis who initiated IL-17i or IL-23i during this study period were included. Persistence of the index biologic and post-discontinuation treatment-free status were assessed using Kaplan-Meier methodology. Propensity score methods with inverse probability of treatment weighting and matching were employed to control potential confounding between treatment cohorts.ResultsThere were 1,751 and 1,721 patients included in the IL-17i cohort and IL-23i cohort, respectively. Persistence rates for IL-17i were 55.7% [95% CI 53.2-58.1%] at the first year and 21.5% [95% CI 18.9-24.2%] at the fourth year, versus 77.7% [95% CI 75.4-79.8%] and 47.8% [95% CI 42.2-53.2%], respectively, for IL-23i. The risk of discontinuation of IL-23i was half that of IL-17i (adjusted hazard ratio [aHR]=0.49 [95% CI 0.44-0.54]). After discontinuation, 19.2% [95% CI 16.1-22.4%] and 31.5% [95% CI 27.8-41.2%] of patients in the IL-17i and IL-23i cohorts, respectively, remained treatment-free for at least 1 year. Patients treated with IL-23i had a lower risk for resuming systemic therapy after biologic discontinuation (aHR=0.57 [95% CI 0.49-0.67]).ConclusionIL-23i was associated with longer persistence and a longer post-discontinuation treatment-free period than IL-17i in patients with psoriasis. These findings may provide actionable insights for healthcare providers and patients as they develop treatment strategies. Future research integrating comprehensive clinical data is warranted to evaluate different treatment strategies, thereby informing clinical decision-making.Weiterlesen

Guselkumab (TREMFYA®) is a fully human IgG1λ monoclonal antibody developed by Johnson & Johnson to selectively target the p19 subunit of interleukin (IL)-23, a cytokine that plays a key role in various immune-mediated inflammatory diseases. Guselkumab is approved in multiple countries worldwide, including the USA and those of the EU, for the treatment of adults with moderate-to-severe plaque psoriasis, active psoriatic arthritis, and moderately-to-severely active ulcerative colitis and Crohn's disease. In September 2025, guselkumab received its first pediatric approvals in the USA for the treatment of pediatric patients 6 years of age and older and weighing ≥ 40 kg who either have moderate-to-severe plaque psoriasis and are candidates for systemic therapy or phototherapy, or who have active psoriatic arthritis. Subsequently, guselkumab was approved in December 2025 in the EU for the treatment of moderate-to-severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy. Johnson & Johnson is currently undertaking phase III development of guselkumab in pediatric patients with Crohn's disease and ulcerative colitis in various countries. This article summarizes the milestones in the development of guselkumab leading to these first pediatric approvals for plaque psoriasis and psoriatic arthritis.Weiterlesen

Dear Editor, Psoriasis is a chronic, immune-mediated inflammatory dermatosis that affects approximately 3% of the adult population and exerts a substantial impact on health-related quality of life (QoL). The plaque-type variant is the most prevalent clinical form, typically involving the trunk and limbs. The anatomical distribution of psoriatic lesions has been demonstrated to play a critical role in shaping the disease burden, with visible and exposed areas contributing disproportionately to psychosocial distress and functional impairment. [...].Weiterlesen

Psoriasis, long thought to be a chronic immune-mediated dermatological disease, is now being reclassified as a systemic inflammatory disease with substantial metabolic and hepatic complications. Psoriasis affects approximately 2-3% of global population and is associated with up to 50% risk of systemic comorbidities. This mini-review examines the evolving understanding of psoriasis pathogenesis, focusing on the interaction of immunological dysregulation, keratinocyte hyperproliferation, and systemic cytokine release. Tumour necrosis factor- alpha (TNF)-α, IL-17, IL-23, and IL-6 are pro-inflammatory mediators that cause cutaneous plaque formation and reach the systemic circulation, leading to insulin resistance, atherogenesis, and liver inflammation. The review identifies common immuno-metabolic pathways, including TNF-α/NF-κB activation, the IL-23/Th17 axis, and dysregulated PI3K/Akt/mTOR signalling, that contribute to psoriatic illness and associated disorders like metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies demonstrate that psoriasis patients have a high prevalence of obesity, type 2 diabetes, dyslipidaemia, regardless of established risk factors, supporting the updated classification of NAFLD as MASLD. These findings lend support to the idea that psoriasis is a multi-organ disease caused by chronic low-grade inflammation. Clinically, this requires a transition from skin-centred treatment to thorough systemic examination and customised, multidisciplinary management. Targeted biologic treatments, such as IL-17 and IL-23 inhibitors, offer potential for lowering both systemic inflammation and cutaneous symptoms. This review supports early screening, metabolic monitoring, and lifestyle changes as critical components of long-term psoriatic therapy. Recognising psoriasis as a systemic condition is critical for improving overall patient outcomes, lowering morbidity, and avoiding long-term consequences.Weiterlesen

AimRisankizumab is a high-cost biologic treatment for chronic plaque psoriasis, an immune-mediated inflammatory disease presenting with painful red scaly skin lesions. Inter-individual heterogeneity in treatment response may be better addressed with personalised rather than fixed dosing. We sought to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to characterise the relationship between risankizumab exposure and treatment response.MethodsA sequential population PK/PD model was developed using real-world data (UK Biomarkers of Systemic Treatment Outcomes in Psoriasis study) comprising serial PK and Psoriasis Area and Severity Index (PASI) measures. Models were built using R (V4.3.1) and nlmixr2 (V2.1.1.9). One and two-compartment PK models were tested. A maximal effect turnover model was used to describe PASI, with drug effect on lesion development rate (Kin).ResultsThe dataset (82 serum risankizumab concentrations; 101 PASI observations) comprised 50 patients with psoriasis (median weight 79.3 kg; age 47 years). PK data were described by a one-compartment model with first-order absorption/elimination. Absorption rate (Ka) was fixed from the literature (0.229). Estimated clearance was 0.34 L/day, and volume of distribution 12.9 L. Baseline PASI at model initiation, drug potency (EC50) and lesion recovery rate (Kout) were estimated at 23.4, 0.11 mg/L and 0.05 day-1, respectively.ConclusionsPharmacokinetic parameters were similar to risankizumab clinical trials. Kout estimates aligned with other psoriasis turnover models, highlighting the capture of disease dynamics that may be applied across drugs. This model may inform personalised dosing based on individual patient characteristics, drug exposure and response, to optimise treatment outcomes.Weiterlesen

The present Part 2 of the updated German S3 guideline on the treatment of psoriasis vulgaris provides recommendations for therapy selection in special clinical situations and in the presence of comorbidities. A major focus of this update is the chapter on screening for tuberculosis as well as therapy selection and management in latent tuberculosis. The recommendations regarding the use of interferon-gamma release assays and the indication for chest radiography have been extensively revised. In addition, the guidance on the suitability of systemic psoriasis therapies in patients with latent tuberculosis and on the need for preventive antituberculous treatment has been thoroughly updated. In the chapter on inflammatory bowel diseases, risankizumab and guselkumab have been added as recommended treatment options, as both agents have recently been approved for the indications Crohn's disease and ulcerative colitis. Further substantial revisions are included in the chapters on patients with a history of malignancy and viral hepatitis.Weiterlesen

No abstract supplied.Weiterlesen