Dupilumab-induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis.

BACKGROUND Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. METHODS Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino-Nasal-Outcome-Test Score (SNOT-22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils. RESULTS Sixty-eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT-22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM-1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down- and IL-4 upregulated in subjects with eosinophil increase. CONCLUSION Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL-4 at baseline developed dupilumab-induced transient eosinophilia. We identified the downregulation of VCAM-1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab-induced eosinophilia

Clinical Presentation and Prognostic Features in Patients with Immunotherapy-Induced Vitiligo-like Depigmentation: A Monocentric Prospective Observational Study

Vitiligo-like depigmentation (VLD) is an immune-related adverse event (irAE) of checkpoint-inhibitor (CPI) treatment, which has previously been associated with a favourable outcome. The aim of this study was to explore clinical, biological and prognostic features of melanoma patients with VLD under CPI-treatment and to explore whether they exhibit a characteristic immune response profile in peripheral blood. Melanoma patients developing VLD under CPI were included in a prospective observational single-center cohort study. We collected and analysed clinical parameters, photographs and serum from 28 VLD patients. They received pembrolizumab (36%), nivolumab (11%), ipilimumab/nivolumab (32%) or clinical trial medications (21%). We performed a high-throughput proteomics assay (Olink), in which we identified a distinct proteomic signature in VLD patients in comparison to non-VLD CPI patients. Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller “freckle-like” macules and a preferential distribution in UV-exposed areas. Patients with previous targeted therapy showed a significantly longer time lapse between CPI initiation and VLD onset compared to non-pre-treated patients (12.5 vs. 6.25 months). Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3. ITGA11 was elevated in the VLD-group when compared to non-VLD-CPI-treated melanoma patients. Our findings demonstrate that on a proteomic level, VLD is characterized by a distinct immune signature when compared to CPI-treated patients without VLD and that therapy responsiveness is reflected by a characteristic immune profile. The pathomechanisms underlying these findings and how they could relate to the antitumoral response in melanoma remain to be elucidated

SARS-CoV-2 Vaccination Rate and SARS-CoV-2 Infection of Health Care Workers in Aerosol-Generating Medical Disciplines

Healthcare workers (HCW) who perform aerosol-generating procedures (AGP) are at high risk of SARS-CoV-2 infection. Data on infection rates and vaccination are limited. A nationwide, cross-sectional study focusing on AGP-related specialties was conducted between 3 May 2021 and 14 June 2021. Vaccination rates among HCW, perception of infection risk, and infection rates were analyzed, focusing on the comparison of gastrointestinal endoscopy (GIE) and other AGP-related specialties (NON-GIE), from the beginning of the pandemic until the time point of the study. Infections rates among HCW developed similarly to the general population during the course of the pandemic, however, with significantly higher infections rates among the GIE specialty. The perceived risk of infection was distributed similarly among HCW in GIE and NON-GIE (91.7%, CI: 88.6–94.4 vs. 85.8%, CI: 82.4–89.0; p < 0.01) with strongest perceived threats posed by AGPs (90.8%) and close patient contact (70.1%). The very high vaccination rate (100–80%) among physicians was reported at 83.5%, being significantly more frequently reported than among nurses (56.4%, p < 0.01). GIE had more often stated very high vaccination rate compared with NON-GIE (76.1% vs. 65.3%, p < 0.01). A significantly higher rate of GIE was reported to have fewer concerns regarding infection risk after vaccination than NON-GIE (92.0% vs. 80.3%, p < 0.01)

SARS-CoV-2 vaccination rate and SARS-CoV-2 infection of health care workers in aerosol-generating medical disciplines

Healthcare workers (HCW) who perform aerosol-generating procedures (AGP) are at high risk of SARS-CoV-2 infection. Data on infection rates and vaccination are limited. A nationwide, cross-sectional study focusing on AGP-related specialties was conducted between 3 May 2021 and 14 June 2021. Vaccination rates among HCW, perception of infection risk, and infection rates were analyzed, focusing on the comparison of gastrointestinal endoscopy (GIE) and other AGP-related specialties (NON-GIE), from the beginning of the pandemic until the time point of the study. Infections rates among HCW developed similarly to the general population during the course of the pandemic, however, with significantly higher infections rates among the GIE specialty. The perceived risk of infection was distributed similarly among HCW in GIE and NON-GIE (91.7%, CI: 88.6–94.4 vs. 85.8%, CI: 82.4–89.0; p < 0.01) with strongest perceived threats posed by AGPs (90.8%) and close patient contact (70.1%). The very high vaccination rate (100–80%) among physicians was reported at 83.5%, being significantly more frequently reported than among nurses (56.4%, p < 0.01). GIE had more often stated very high vaccination rate compared with NON-GIE (76.1% vs. 65.3%, p < 0.01). A significantly higher rate of GIE was reported to have fewer concerns regarding infection risk after vaccination than NON-GIE (92.0% vs. 80.3%, p < 0.01)

The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.Peer reviewe

Comprehensive Approach: Current Status on Patient Education in Atopic Dermatitis and Other Allergic Diseases

Allergic diseases are characterized by a complex complex chronic pathophysiology. Therapeutic patient education (TPE) programs are an important part of health care for allergic patients. These programs aim to increase the patient's adherence to evidence-based treatment and improve their ability to cope with the disease. TPE led by a multiprofessional team covers the complex pathogenesis of the disease, trigger factors, nursing and dietary issues, and the broad variety of treatment options available including psychological and behavioral aspects.Regarding atopic dermatitis (AD), randomized, controlled studies have demonstrated the beneficial effects of delivering structured group training to children, their caregivers, and adult patients with AD. Such intervention achieved substantial improvements in quality of life and objective clinical disease parameters. Besides AD, training programs have also been developed and evaluated for patients with anaphylaxis and asthma. This article provides an overview of the multitude of TPE concepts and their impact on subjective and objective outcomes. It focuses on AD but also sheds light on other allergic diseases such as anaphylaxis and asthma. Keywords: Anaphylaxis; Atopic dermatitis; Patient care; Therapeutic patient education programs

Patch test results in patients with suspected contact allergy to shoes: Retrospective IVDK data analysis 2009-2018.

BACKGROUND Allergic contact dermatitis caused by shoes is common and new relevant allergens have been identified. OBJECTIVES To investigate the pattern of type IV sensitization in patients with suspected allergic contact dermatitis of the feet related to shoes as a presumed culprit trigger. METHODS Retrospective analysis of data of the Information Network of Departments of Dermatology (IVDK), 2009-2018. RESULTS Six hundred twenty-five patients with presumed shoe dermatitis were identified in a cohort of 119 417 patients. Compared to patients with suspected contact sensitization from other allergen sources (n = 118 792), study group patients were more frequently sensitized to potassium dichromate (10.8% vs 3.5%), colophony (7.2% vs 3.7%), mercaptobenzothiazole (MBT; 4.0% vs 0.6%), mercapto mix (4.6% vs 0.6%), and p-tert-butylphenol formaldehyde resin (1.6% vs 0.5%). Sensitizations to urea formaldehyde resin, melamine formaldehyde resin, glutaraldehyde, tricresyl phosphate, and phenyl glycidylether were rare. Moreover, reactions to compounds in the leather or textile dyes test series were scarce. CONCLUSION A distinct sensitization pattern was observed in patients with suspected allergy to shoe materials. Although substances with low sensitization rates should be removed from the leather and shoe patch test series, novel potential allergens should be added

Bioklimatisches Informationssystem Bayern: ein Service der UFS (Schlussbericht zum Forschungsvorhaben)

Mit BioClis wurde ein Werkzeuggeschaffen, das der Bayerischen Staatsregierung und der Bevölkerung die flächenhafte Bewertung des aggregierten Gesundheitsrisikos durch Hitze-und Kältestress, sowie Luftschadstoffe in Bayern ermöglicht. Als webbasiertes Informationssystem liefert BioClis tagesaktuelle, flächendeckende und farbcodierte Analysen und Vorhersagen. Kern ist ein modularer, flexibler und erweiterbarer Umweltdatenprozessor, der auf den informationstechnologischen Entwicklungen der AlpEnDAC Plattform aufbaut und verschiedenste Datenquellen aus epidemiologischen Erhebungen, in-situ Messungen, Satelliten und numerischen Modellen integriert. Je nach Gesundheitsrisiko wurden jeweils im Informationssystem allgemeine Maßnahmen und Empfehlungen in den Bereichen Prävention und Verhalten formuliert. BioClis liefert so einen informationstechnologischen und methodischen Baustein zur Förderung von proaktivem Verhalten und Handeln bei der Anpassung an den Klimawandel im Bereich der Gesundheit. Das Projekt adressiert die Forderung nach innovativen Informationssystemen und die Unterstützung insbesondere von Vorsorge-, Diagnostik und Therapiemaßnahmen. BioClis trägt dazu bei, negative gesundheitliche Auswirkungen von Umweltstressoren und des Klimawandels durch geeignete Präventionsmaßnahmen zu reduzieren oder zu verhindern somit die Lebensqualität zu erhöhen. BioClis leistet damit einen konkreten Beitrag zur Umsetzung der Bayerischen Klimaanpassungsstrategie (BayKLAS) im Handlungsfeld menschliche Gesundheit

One year of the COVID-19 pandemic in dental medical facilities in Germany: a questionnaire-based analysis

(1) Background: The COVID-19 pandemic forced healthcare workers to adapt to challenges in both patient care and self-protection. Dental practitioners were confronted with a potentially high possibility of infection transmission due to aerosol-generating procedures. This study aims to present data on healthcare worker (HCW) screening, infection status of HCWs, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic in dental facilities. (2) Methods: Dental facilities were surveyed nationwide using an online questionnaire. The acquisition of participants took place in cooperation with the German Society for Dentistry, Oral and Maxillofacial Medicine. (3) Results: A total of 1094 private practices participated. Of these, 39.1% treated fewer than 600 patients per quarter and 59.9% treated over 600 patients per quarter. Pre-interventional testing was rarely performed in either small (6.6%) or large practices (6.0%). Large practices had a significantly higher incidence of at least one SARS-CoV-2-positive HCW than small practices (26.2% vs.14.4%, p < 0.01). The main source of infection in small practices was the private environment, and this was even more significant in large practices (81.8% vs. 89.7%, p < 0.01). The procedure count either remained stable (34.0% of small practices vs. 46.2% of large practices) or decreased by up to 50% (52.6% of small practices vs. 44.4% of large practices). Revenue remained stable (24.8% of small practices vs. 34.2% of large practices) or decreased by up to 50% (64.5% of small practices vs. 55.3% of large practices, p = 0.03). Overall, employee numbers remained stable (75.5% of small practices vs. 76.8% of large practices). A vaccination readiness of 60–100% was shown in 60.5% (n = 405) of large practices and 59.9% (n = 251) of small practices. (4) Conclusion: Pre-interventional testing in dental practices should be increased further. Economic challenges affected small practices as well as large practices. Overall, a steady employee count could be maintained. Vaccination readiness is high in dental practices, although with some room for improvement