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Background & Aims: Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs. lenvatinib in a large, multicenter real-world population. Methods: This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared. Results: In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib (p = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib (p = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort (p = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months. Conclusions: Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib. Impact and implications: The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib.

Background Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients. Methods The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores. Results At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4–24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m2) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT. Conclusion Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors.

Background: Allergic diseases, especially inhalation allergies, have reached epidemic levels and environmental factors play an important role in their development. Climate change influences the occurrence, frequency, and severity of allergic diseases. Methods: The contents of this article were selected by the authors and developed section by section according to their expertise and the current state of knowledge. The sections were then discussed and agreed upon amongst all authors. Results: The article highlights direct and indirect effects of climate change on allergies. It goes into detail about the connections between climate change and (new) pollen allergens as well as (new) occupational inhalation allergens, explains the effects of climate change on the clinical picture of atopic dermatitis, discusses the connections between air pollutants and allergies, and provides information about the phenomenon of thunderstorm asthma. Conclusions: There is a need for action in the field of pollen and fungal spore monitoring, allergy and sensitisation monitoring, urban planning from an allergological perspective, and changes in the working environment, among others.

Abstract Background The American Bashkir Curly Horse is frequently advertised to horse‐allergic riders and claimed to be a so‐called hypoallergenic breed that elicits fewer symptoms. Previous studies quantifying selected allergens in different breeds did not find a reduced allergen content in Curly Horses. Here, we provide a comprehensive proteomic analysis of horse hair extracts and a molecular analysis of the major allergen Equ c 1 with the aim of identifying differences in the Curly Horse breed that might explain their presumed reduced allergenic potential. Methods Horse hair extracts were prepared from Curly and American Quarter Horse breeds, separated by gender and castration status, extracts from other breeds served as controls. Extracts and native Equ c 1 (nEqu c 1) were analyzed by mass spectrometry. IgE‐binding capacities of nEqu c 1 and its recombinant variants were tested by ELISA using sera of patients sensitized to horses. Structures and ligand binding abilities were analyzed by computational modeling and fluorescence quenching assays. Results All known respiratory horse allergens are present in hair extracts of Curly and Quarter Horses and share identical allergen‐specific peptides. Lipocalin allergens are the most abundant proteins in horse hair extracts and contain several post‐translational modifications. We identified two new variants of Equ c 1 that have similar IgE‐binding capacities but show structural differences in their binding cavities and altered ligand binding behavior. There are no differences in IgE‐binding of Equ c 1 derived from Curly Horses compared to other horse breeds. Conclusion Our data do not support the claim that Curly Horses are less allergenic than other breeds.

The monitoring of physiological parameters using wearable (bio-) sensors of military personnel is a progressing process within the military environment. It sets high demands on such devices, in order to support healthcare and performance of the personnel. To get an ovierview of the current status of the use, the evaluation and the implementation in the military, in May 2021, the Multinational Medical Coordination Centre / European Medical Command has organized an expert workshop about ‘Biosensors Supporting Healthcare in Missions’. Three thematic clusters were addressed: ‘Human Performance and Readiness’; ‘Health and Medical Management Applications’ and ‘Ethical and Legal Aspects of the Use of Biosensors’.

Climate change and extreme weather events are an increasing challenge for society and the economy, including the transport sector. A sustainable and resilient transportation system therefore requires information on the temporal and spatial pattern of risks induced by climate change and the assessment of resulting vulnerabilities. Such analyses in the past were usually made separately for each mode of transport based on different observational and climate model datasets and using different methodological approaches to analyse climatic changes and their impacts on the transport infrastructure. Within the research network “BMDV Network of Experts” an intermodal perspective is taken on transportation. Common observational and climate model datasets as well as a standardized analysis framework were coordinated and agreed upon to form the basis for comparable climate impact assessments for roads, railways and inland waterways. This manuscript introduces the climatological datasets and methodological approaches for the climate change and climate impact analysis used for the transportation sector and beyond. Selected results on the projected increases of extreme temperature and heavy precipitation are exemplarily presented in order to illustrate the need for developing climate change adaptation measures for the German inland transport system.

Abstract Background Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. Methods Sixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. Results No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. Conclusion The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Objectives: In this study, we applied novel nasal filters to assess animal allergen exposure of veterinary staff during their normal daily routine. Methods: Rhinix nasal filters were worn during work by 94 employees at different veterinary practices and 18 employees at a research institute, who acted as controls representing an animal-free environment. Contact with animals and the activities performed were documented by the study participants using a short questionnaire. Major allergens of cats (Fel d 1), dogs (Can f 1), and domestic mites (DM) were measured using fluorescence enzyme immunoassays. Results: At the practices, Can f 1 was detected in 98%, Fel d 1 in 82%, and DM allergens in 39% of the samples. Allergens were also detected in some control samples (6% for Can f 1, 39% for Fel d 1, and 17% for DM) but in very low concentrations. There was a highly significant difference between allergen levels in veterinary workers who treated at least one cat or dog during the sampling period and those who did not (2.66 vs. 0.70 ng/filter for Can f 1 and 1.01 vs. 0.20 ng/filter for Fel d 1). The amount of sampled Fel d 1 increased significantly with increasing duration of contact with cats. This effect was not observed for Can f 1. Conclusions: The majority of veterinary workers are exposed to dog and cat allergens, even without direct contact with these animals. Rhinix nasal filters may be considered a simple and easily applicable method for monitoring personal allergen exposure.

Climate changes have promoted an increased fungal infection of maple trees with Cryptostroma corticale, the causative agent of sooty bark disease. The hosts of C. corticale are maples, and since the early 2000s the fungus has been appearing more frequently in European forests, due to the droughts and hot summers of recent years. Infestation by C. corticale discolors the wood and makes it unusable for further processing, which leads to considerable economic damage in the timber industry. Therefore, the occurrence and spread of sooty bark disease raise serious problems. In addition to forestry and economic problems, the conidiospores of C. corticale can also cause health problems in exposed wood workers and they can trigger hypersensitivity pneumonitis (HP). Since the spores, which are deposited over the entire area under the bark of infected trees, can spread during processing, exposed workers must take special precautions to protect themselves against exposure. If an occupational disease is nevertheless suspected following exposure to C. corticale, valid diagnostics are required to confirm possible HP and derive appropriate therapies and exposure reduction or avoidance. Diagnosis of HP is based on several criteria, one of them is the detection of specific IgG in patient's serum against the potentially triggering antigens, in this case C. corticale antigens. To produce a diagnostic tool to measure C. corticale specific IgG, which is not commercially available so far, spores and mycelial material from ITS-sequenced strains of C. corticale was prepared and analyzed. These biochemically characterized extracts of spore and mycelial antigens were biotinylated and coupled to Streptavidin-ImmunoCAPs. To validate these diagnostic test tools the first step is to measure the concentration of C. corticale specific IgG in sera of healthy non-exposed and healthy exposed subjects to establish cut-off values. Suitable participants were recruited and the individual exposure to C. corticale and symptoms experienced during or after working with infected maple trees were recorded using questionnaires. Finally, diagnostic tools for serological testing in suspected cases of HP by C. corticale were created and evaluated. The following article provides recommendations for the treatment and disposal of infected damaged wood and for occupational health protection procedures. Secondly, the diagnosis of HP induced by exposure to C. corticale as an occupational disease is described including the verification of newly developed serological test tools for antigens of C. corticale.

Abstract Objective Standardised quantitative analysis of the humoral immune response to SARS‐CoV‐2 antigens may be useful for estimating the extent and duration of immunity. The aim was to develop enzyme‐linked immunosorbent assays (ELISAs) for the quantification of human IgG antibodies against SARS‐CoV‐2 antigens. Methods Enzyme‐linked immunosorbent assays were developed based on monoclonal antibodies against human IgG and recombinant SARS‐CoV‐2 antigens (Spike‐S1 and Nucleocapsid). The WHO 67/086 immunoglobulin and WHO 20/136 SARS‐CoV‐2 references were used for standardisation. Sera of a study group of COVID‐19‐positive subjects (n = 144), pre‐pandemic controls (n = 135) and individuals vaccinated with BioNTech–Pfizer BNT162b2 vaccine (n = 48) were analysed. The study group sera were also tested using EuroImmun SARS‐CoV‐2‐ELISAs and a quantitative S1‐specific fluorescence enzyme immunoassay (FEIA) from Thermo Fisher. Results The ELISA results were repeatable and traceable to international units because of their parallelism to both WHO references. In the study group, median anti‐S1‐IgG concentrations were 102 BAU mL−1, compared to 100 and 1457 BAU mL−1 in the vaccination group after first and second vaccination, respectively. The ELISAs achieved an area under the curve (AUC) of 0.965 (S1) and 0.955 (Nucleocapsid) in receiver operating characteristic (ROC) analysis, and a specificity of 1 (S1) and 0.963 (Nucleocapsid) and sensitivity of 0.903 (S1) and 0.833 (Nucleocapsid) at the maximum Youden index. In comparison, the commercial assays (S1‐FEIA, S1 and Nucleocapsid ELISA EuroImmun) achieved sensitivities of 0.764, 0.875 and 0.882 in the study group, respectively. Conclusions The quantitative ELISAs to measure IgG binding to SARS‐CoV‐2 antigens have good analytical and clinical performance characteristics and units traceable to international standards.