Browsing by Author "Becker, Sven"

Zusammenfassung Hintergrund Die Allergologie ist in Deutschland interdisziplinär organisiert. Zur Steuerung und Verbesserung fachbereichsübergreifender Kooperationen ist ein Überblick über die aktuelle Versorgungssituation notwendig. Methode Zwischen Januar und Februar 2022 wurden online und postalisch Fragebögen an Leitungen stationärer klinischer Fachbereiche versendet, denen die meisten allergologischen Krankheitsbilder zugeordnet werden (Dermatologie, HNO, Pneumologie, Pädiatrie, Umwelt/Arbeitsmedizin, Gastroenterologie; n = 899). Ergebnisse Die Rücklaufquote betrug 52,1%. Allergologische Abteilungen von Dermatologie, HNO und Pneumologie waren überwiegend in Ballungsgebieten verfügbar (> 100 000 Einwohner), während Antworten pädiatrischer Abteilungen größtenteils aus kleinen Städten kamen. 76,8% der befragten Kliniken gaben bestehende interdisziplinäre Behandlungskonzepte mit anderen Fachrichtungen an. Kliniken der Pädiatrie und der Pneumologie vermeldeten, insbesondere in kleineren Städten mit < 100 000 Einwohnern, unterproportional wenig interdisziplinäre Behandlungskonzepte mit Dermatologie und HNO‐Kliniken. Diagnostik und Therapie der allergischen Rhinitis wurden insbesondere durch die Abteilungen für HNO und Asthma vor allem durch die Abteilungen für Pneumologie durchgeführt. Die Betreuung der weiteren allergologischen Erkrankungen wurde am häufigsten aus der Dermatologie und Pädiatrie zurückgemeldet. Schlussfolgerungen In Ballungsgebieten übernehmen beteiligte Fachbereiche die allergologische Versorgung kooperativ. Ein großes Spektrum der Versorgung wird in Kooperationen mit dermatologischen Kliniken abgedeckt. In ländlicheren Gebieten sind Kooperationen seltener, wobei hier die Versorgung vor allem durch pädiatrische Abteilungen erfolgt, was im Vergleich zu Ballungsgebieten das eingeschränktere Leistungsangebot erklären könnte.

Abstract Background The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases. Methods ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system. Results The present ICP (integrated care pathways) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers. Discussion A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.

Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the reduction of vessel density and an increase in vascular permeability and tumor cell apoptosis after CAP application. Solid tumors in the chorioallantoic membrane of chicken embryos were treated with CAP and evaluated with respect to effects of CAP on embryo survival, tumor size, and tumor morphology. Furthermore, intratumoral blood vessel density, apoptotic cell death and the tumor-associated microcirculation were investigated and compared to sham treatment. Treatment with CAP significantly reduced intratumoral vessel density while increasing the rate of intratumoral apoptosis in solid tumors. Furthermore, CAP treatment increased vascular permeability and attenuated the microcirculation by causing vessel occlusions in the tumor-associated vasculature. These effects point out the potential of CAP as a promising and yet underrated therapeutic modality for addressing the tumor vasculature in the treatment of solid tumors.

Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.

Summary Background Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation. Methods Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899). Results The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (> 100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with < 100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics. Conclusions In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.

Background: Differential diagnosis between ragweed and mugwort pollen allergy represents a large clinical problem in areas where both plants are present. The aim of this study was to investigate ragweed-and mugwort-sensitized patients to identify specific IgE reactivity profiles. Results were correlated to clinical findings such as medical history and health-related quality of life (HRQL). Methods: Seventy-four patients with allergic rhinoconjunctivitis between July and October were examined and underwent in vivo tests (skin-prick test [SPT] and nasal provocation). Sera were evaluated for IgE reactivity to mugwort and ragweed pollen extracts, major (Art v 1; Amb a 1) and minor (profilin and calcium-binding protein) allergens. HRQL was evaluated using a standardized questionnaire. Results: Seventy-one patients revealed positive SPT reactivity against mugwort and 60 patients against ragweed extracts. Of these patients, 74 revealed IgE antibodies against mugwort extracts, whereas anti-Art v 1 antibodies were detectable in 50 individuals. Fifty-five patients showed IgE antibodies against natural ragweed extracts; anti-Amb v 1 antibodies were detected in six cases only. Using standardized clinical history and HRQL questionnaires we were not able to detect any differences within different reactivity patterns. Conclusion: Within the investigated population of 74 weed-allergic patients the prevalence of true mugwort and ragweed sensitization can be calculated as 68 and 8%. High prevalence of ragweed sensitization when testing with full extracts can be explained by cross-reactivity between other weeds, e. g., mugwort rather than cosensitization. Differences in medical history and HRQL between different reactivity patterns were not detectable. (Am J Rhinol Allergy 26, 31-35, 2012; doi: 10.2500/ajra.2012.26.3698)

Summary Background Chronic rhinosinusitis with nasal polyps (CRSwNP), an inflammatory disease of the paranasal mucosa, is primarily characterized by type 2 inflammation. Three antibodies (dupilumab, omalizumab, and mepolizumab) are now approved for the treatment of severe CRSwNP. Documentation of disease severity during the course of treatment is essential. Methods A literature search of Medline, PubMed, and the national and international trial and guideline register, and the Cochrane Library was performed to analyze the immunology of CRSwNP and determine the evidence for the effect of dupilumab, omalizumab, and mepolizumab in this disease. This has resulted in 3 position papers prepared by our group of authors, which form the basis of this summarizing review. Results Based on the information from the international literature, recommendations for the use of dupilumab, omalizumab, and mepolizumab in CRSwNP in the German health care system are given by an expert panel. Conclusion Dupilumab, omalizumab, and mepolizumab are approved for patients 18 years of age and older with CRSwNP as add-on therapy to intranasal corticosteroids when, for dupilumab and mepolizumab, therapy with systemic corticosteroids and/or surgery does not achieve sufficient disease control. Therapy with omalizumab is indicated when therapy with intranasal corticosteroids does not result in sufficient disease control. Dedicated recommendations for the documentation of the use in the German health care system are given, which are based on the position papers of our author group already published on this topic.

Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation. Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. Stimulation of CD95 in cells expressing a non-phosphorylatable caspase-8-T273A mutant in a rescue experiment or in Plk3-KO cells generated by CRISPR/Cas9 reduces the processing of caspase-8 prominently. Low T273 phosphorylation correlates significantly with low Plk3 expression in a cohort of 95 anal tumor patients. Our data suggest a novel mechanism of kinase activation within the Plk family and propose a new model for the stimulation of the extrinsic death pathway in tumors with high Plk3 expression.

Introduction: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. Methods: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). Results: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. Conclusion: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts.

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1 beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1 beta was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL-5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES. Copyright (C) 2012 S. Karger AG, Basel

Conclusions: The limitation in olfactory function in patients with seasonal allergic rhinitis (AR) can be ascribed to an increase in eosinophilic and mast cell activity in the olfactory cleft. Therefore, the decrease in olfactory functions seems to be predominantly caused by the inflammation of the epithelium and not by the obstruction of the nose caused by the inflammation. Objective: Olfactory dysfunction is frequently seen in patients with AR; however, little is known about the underlying pathophysiological mechanisms. Therefore, the aim of the present study was to examine the olfactory function in patients with seasonal or perennial AR, and to correlate the results with data obtained by analysis of nasal secretion and obstruction. Methods: Olfactory function was tested using the SniffinSticks test in patients with seasonal or perennial AR and in a control group. Nasal secretion analysis included eosinophilic cationic protein (ECP) and tryptase testing. Nasal obstruction was evaluated by rhinomanometry. Results: Patients with AR (seasonal and perennial) showed impaired olfactory functions in comparison with the control group. Nasal secretion analysis showed increased values of ECP and tryptase in the seasonal group in comparison with controls. Rhinomanometry showed no differences in nasal flow between the three groups.

Summary Two employees of the National Health Service (NHS) in England developed severe allergic reactions following administration of BNT162b2 vaccine against COVID-19 (coronavirus disease 2019). The British SmPC for the BNT162b2 vaccine already includes reference to a contraindication for use in individuals who have had an allergic reaction to the vaccine or any of its components. As a precautionary measure, the Medicines and Healthcare products Regulatory Agency (MHRA) has issued interim guidance to the NHS not to vaccinate in principle in “patients with severe allergies”. Allergic reactions to vaccines are very rare, but vaccine components are known to cause allergic reactions. BNT162b2 is a vaccine based on an mRNA embedded in lipid nanoparticles and blended with other substances to enable its transport into the cells. In the pivotal phase III clinical trial, the BNT162b2 vaccine was generally well tolerated, but this large clinical trial, used to support vaccine approval by the MHRA and US Food and Drug Administration, excluded individuals with a “history of a severe adverse reaction related to the vaccine and/or a severe allergic reaction (e.g., anaphylaxis) to a component of the study medication”. Vaccines are recognized as one of the most effective public health interventions. This repeated administration of a foreign protein (antigen) necessitates a careful allergological history before each application and diagnostic clarification and a risk–benefit assessment before each injection. Severe allergic reactions to vaccines are rare but can be life-threatening, and it is prudent to raise awareness of this hazard among vaccination teams and to take adequate precautions while more experience is gained with this new vaccine.

Background/Aim: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy. Materials and Methods: Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary human cells from fresh tumor specimens. Results: All cell lines showed reliable growth in all cell culture methods. The spheroids showed significant delay of growth and/or necrosis compared to control groups when exposed to current standard chemotherapeutic regimens. Single 3D spheroids ready for therapy susceptibility testing could be generated from actual tumor specimens after enzymatic and mechanical separation. Conclusion: In its current form, this single spheroid-based in vitro assay was able to test individual therapy susceptibility to current standard therapy regimens or, potentially, for testing new targeted drugs in HNSCC treatment. With recent discoveries regarding tumor heterogeneity and individual mutation status, a reliable assay is a prerequisite for personalized therapy in head and neck cancer.