Occupational anaphylaxis-Data from the anaphylaxis registry.

BACKGROUND: Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work-related anaphylactic episodes. METHODS: Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management. RESULTS: Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects (n = 186, 82.7%) followed by food (n = 27, 12.0%) and drugs (n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom-induced anaphylaxis to a group of non-occupational insect anaphylaxis in adults (n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee-induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p = .044). In the occupational- versus non-occupational adults with food-induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently (n = 486; 20% vs. 10%), although this was not significant. CONCLUSION: Our data demonstrate the impact of venom allergy in work-related anaphylaxis. Foods and drugs are less frequently elicitors, and latex-induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis.

Fatal and Near-Fatal Anaphylaxis: Data From the European Anaphylaxis Registry and National Health Statistics.

BACKGROUND: Anaphylaxis is a serious systemic reaction-data on fatal and near-fatal reactions are limited. OBJECTIVE: To better understand clinical patterns and risks factors of severe anaphylaxis by a deep analysis of data from fatal and near-fatal anaphylaxis. METHODS: Data from the European Anaphylaxis Registry on fatal/near-fatal anaphylactic reactions and national data on anaphylaxis fatalities were investigated. RESULTS: A total of 305 fatal/near-fatal reactions among children and adults including 35 fatalities from the European Anaphylaxis Registry were identified. The most frequent elicitors were drugs, insects, and food. Male patients (66%/60%) were more frequently affected. Male sex, higher age, concomitant mastocytosis, and cardiovascular disease were associated with a more severe outcome. With increasing reaction severity, skin symptoms were less frequently observed (45% of fatal reactions). In parallel, anaphylaxis mortality rates were studied. The data show that anaphylaxis mortality rates increased in Germany from 0.48 (2009) to 0.59 per 1,000,000 population per year (2020). This increase was apparent only in the female population. In this data set, drugs were the most frequent elicitor of anaphylaxis fatalities, and the rate for this increased over time. CONCLUSIONS: We identified not only elicitors but also individual factors to be associated with an increased risk of fatal anaphylaxis. Such patients should be recognized and managed with great caution. The increase in drug-induced fatalities points to the need for a better allergological care of patients suffering from drug hypersensitivity.

Food-Induced Anaphylaxis: Data From the European Anaphylaxis Registry.

BACKGROUND: Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years. OBJECTIVES: To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA). METHODS: We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA. RESULTS: We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V = 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V = 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V = 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V = 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR = 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR = 1.78; CI, 1.09-2.95). CONCLUSIONS: Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA.

Health-Related Quality of Life and Mental Health in Drug Hypersensitivity Reactions and Drug-Induced Anaphylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Drug hypersensitivity reactions (DHRs) are adverse drug reactions (ADRs) that are particularly impactful on health-related quality of life (HRQoL) and mental health. Although the role of HRQoL as an important patient-reported outcome has been recognized in past years, HRQoL and mental health in patients with ADRs are still poorly investigated. OBJECTIVE: To evaluate the prevalence, severity, and risk factors of HRQoL and mental health in DHRs, with a particular focus on drug-induced anaphylaxis. METHODS: We searched the MEDLINE, Scopus, and American Psychological Association PsycArticles databases to identify all studies up to December 31, 2022 that included subjects with at least one episode of DHR and assessments of mental health and/or quality of life. Results were reported as qualitative and quantitative analyses, with meta-analyses after assessment for risk of bias and heterogeneity. RESULTS: A total of 45 observational studies were included. Overall, a high prevalence of depression (up to 51.4%; odd ratio = 2.94; 95% CI, 1.42-6.10) and anxiety (up to 48%; odd ratio = 3.92; 95% CI, 1.91-8.05) were reported compared with healthy subjects. The HRQoL was significantly affected, especially in the case of drug-induced anaphylaxis (mean score, +5.88; 95% CI, 0.77-10.98). CONCLUSIONS: Despite the scarce and heterogeneous studies on this topic, the review shows that HRQoL and mental health are markedly affected after ADRs. A better assessment of HRQoL and characterization of patients' mental status may improve the efficacy of therapeutic strategies, which should include psychological support.

Health-related quality of life in food and venom induced anaphylaxis and role of influencing factors.

The impact on health-related quality of life (HRQL) plays a key role for patients suffering from allergies and anaphylaxis. In this narrative review we review the HRQL in allergic patients suffering from food and venom allergy, both being the most frequent elicitors of severe allergic, potential life-threatening reactions and provide an overview on the current knowledge and identified gaps. The data show that for food and venom allergy standardized assessment tools to measure HRQL are available and have been successfully applied. Our analysis shows that multiple factors can modulate HRQL in these patient groups. These include sociodemographic data like patients' age and sex, fear of accidental reactions but also external factors like the social environment and the appreciation of the seriousness of the condition by others. External factors may have a significant impact on HRQL and should be considered in patient-related outcome assessments to avoid biased measurements possibly affecting the results. The assessment of the quality of life in the context of specific immunotherapy should consider lifestyle factors and ideally, the individual change in HRQL should be measured. Although there are many data indicating a negative impact on HRQL in food allergic children and their caregivers, limited data are existing from adults with food allergy and venom allergic patients from all age groups. Also, the use of standardized questionnaires should be extended to allow for a better comparability of results between studies. Therefore, translation to additional languages is necessary. Taken together, the eliciting allergen, the severity of the allergic disease but moreover multiple external factors impact the outcome in HRQL and should be considered in HRQL assessment.

An interdisciplinary approach to characterize peanut-allergic patients-First data from the FOOD@ consortium.

Background: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. Methods: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. Results: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. Conclusion: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies.

Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells.

BACKGROUND/AIM: The influence of surgical interventions and anaesthesiological procedures on tumour progression was investigated as early as the 1920s. In current cancer management, the perioperative phase is increasingly being considered a vulnerable period with an increased risk of tumour cell dissemination due to medication, surgical manipulation, and immunosuppression. The extent to which narcotics administered in the perioperative setting influence the oncological outcomes of patients with pancreatic cancer is still unclear. MATERIALS AND METHODS: To investigate the effect of propofol and etomidate on the proliferation, cell-cycle distribution, apoptosis, and necrosis of pancreatic tumour cells in vitro, PaTu 8988t and Panc-1 pancreatic cancer cells were treated with 0-1,000 µM propofol or etomidate for 24 h each. Cell proliferation was measured with enzyme-linked immunosorbent-bromodeoxyuridine assay. The apoptosis rate was analysed with annexin V staining and the cell-cycle distribution with flow cytometry. RESULTS: Propofol at 1,000 µM induced apoptosis and inhibited cell proliferation. The cell cycle showed an increased S-phase and reduced cells in the G1-phase. At 100 µM, propofol significantly inhibited proliferation of the pancreatic cancer cell line PaTu 8988t and reduced cells in the G2-phase in the cell cycle. Etomidate had no effects on cell-cycle distribution, proliferation, apoptosis, and necrosis at the concentrations used. CONCLUSION: In this study, propofol was shown to have anticancer effects by induction of apoptosis and inhibition of cell proliferation, while etomidate did not affect pancreatic cancer cells. However, it is too early to make any recommendation for changes in clinical practice and further clinical studies are warranted to investigate the effect of anaesthetics on cancer progression.

Elicitors and phenotypes of adult patients with proven IgE-mediated food allergy and non-immune-mediated food hypersensitivity to food additives.

BACKGROUND: Food allergy is a growing health concern with a prevalence of 2%-3% in the adult population in Europe. Non-immune-mediated food hypersensitivities, which include reactions after ingestion of food additives, affect 1% of adults and may resemble IgE-induced allergic reactions without identifiable immunologic sensitization. A double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for the diagnosis of any food hypersensitivity. OBJECTIVE: We analysed a large group of adult patients with suspected food hypersensitivity, who had undergone DBPCFC, to better understand IgE-mediated food allergy and non-immune-dependent food hypersensitivity to food additives in adults regarding elicitors, symptoms and positivity rates of oral challenges. METHODS: Data from 541 patients with suspected food hypersensitivity were analysed, who underwent an oral food challenge between 2010 and 2019. RESULTS: IgE-dependent food allergy was confirmed in 114 of 329 adult patients (34.6%). The confirmation rate was lower in the group of patients with suspected non-immune-mediated reactions to food additives (65 of 286, 22.7%). Urticaria and angioedema appeared more frequently in patients with IgE-mediated food allergies. By contrast, flush and diarrhoea were the most frequent symptoms after a challenge in the group with the non-immune-mediated reactions to food additives. Wheat and celery were the most frequently identified food allergens in adults, whereas colourings and preservatives were the most frequent elicitors of non-immune-mediated food hypersensitivity. CONCLUSION: The importance of oral food challenges for the diagnosis of food hypersensitivity is confirmed. IgE-dependent food allergy is more frequently proven, reaching a positivity rate of one-third and only about 20% for non-immune-mediated hypersensitivity. Future studies should elaborate on the mechanisms of non-immune-mediated food hypersensitivity and the clinical impact of cofactors in this setting.

Phase Angle Is a Stronger Predictor of Hospital Outcome than Subjective Global Assessment-Results from the Prospective Dessau Hospital Malnutrition Study.

This prospective cohort study of 16,943 consecutive patients compared phase angle (PhA, foot-to-hand at 50 kHz) and subjective global assessment (SGA) to predict outcomes length of hospital stay (LOS) and in-hospital mortality in patients at risk of malnutrition (NRS-2002 ≥ 3). In 1505 patients, the independent effects on LOS were determined by competing risk analysis and on mortality by logistic regression. In model I, including influence factors age, sex, BMI, and diagnoses, malnourished (SGA B and C) patients had a lower chance for a regular discharge (HR 0.74; 95%CI 0.69−0.79) and an increased risk of mortality (OR 2.87; 95%CI 1.38−5.94). The association of SGA and outcomes regular discharge and mortality was completely abrogated when PhA was added (model II). Low PhA reduced the chance of a regular discharge by 53% in patients with a PhA ≤ 3° (HR 0.47; 95%CI 0.39−0.56) as compared to PhA > 5°. Mortality was reduced by 56% for each 1° of PhA (OR 0.44; 95%CI 0.32−0.61). Even when CRP was added in model III, PhA ≤ 3° was associated with a 41% lower chance for a regular discharge (HR 0.59; 95%CI 0.48−0.72). In patients at risk of malnutrition, the objective measure PhA was a stronger predictor of LOS and mortality than SGA.

[Influence of nut and peanut allergy on the quality of life of adults]. / Einfluss der Nuss- und Erdnussallergie auf die Lebensqualität bei Erwachsenen.

BACKGROUND: Health-related quality of life is negatively affected in patients with food allergies. AIM: Analysis of health-related quality of life of adults allergic to tree nuts or peanuts. METHODS: Health-related quality of life was analysed via the Food Allergy Quality of Life Questionnaire - Adult Form (FAQLQ-AF) and the Short Form 12 (SF12) questionnaire. In addition, a diagnostic workup including a detailed patient history, skin prick test and analysis of specific IgE was performed. An oral food challenge was offered to all patients. RESULTS: Food allergic patients (n = 63) reported an average burden of 3.91 ± 1.41 points on the FAQLQ-AF and 3.31 ± 1.03 points on the Food Allergy Independent Measure (FAIM), a measure for the perceived disease severity. A higher mean FAIM score was the most important predictor of higher results (worse quality of life) in the FAQLQ-AF. The SF12 questionnaire was not able to discriminate between food allergic patients and healthy controls (n = 16). CONCLUSION: A tree nut and/or peanut allergy was perceived as an impairment of health-related quality of life, which is directly associated with the perceived severity of disease. Disease-specific quality of life questionnaires can capture the burden associated with peanuts or tree nuts allergies.

[Management of severe nut allergy in adults]. / Management einer schweren Nussallergie im Erwachsenenalter.

We present a case of walnut allergy in a 24-year-old man. The allergy work up revealed sensitization to walnut including a positive skin prick test and a high value of walnut-specific IgEs. The patient showed an anaphylactic reaction during the double blind placebo-controlled food challenge, to a cumulative dose of 3.723 g of walnut protein. The oral food challenge resulted in counseling regarding strict walnut avoidance and optimization of the emergency management. At follow-up the patient reported that having adhered to the recommended dietary measures resulted in no further allergic reactions.

Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta-3-mediated Cell Migration in Pancreatic Carcinoma.

Introduction: Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies in humans. The main reason for its unfavourable prognosis is the combination of rapid tumour growth, early-onset metastasis and currently still inadequate diagnostic and therapeutic options. Thus, only very few patients are eligible for radical resection of the primary tumour as the only curative treatment option available so far. In the perioperative period, tumour progression and metastasis are facilitated by the activation of key signalling pathways and the altered regulation of transcription factors. Various tumour entities have shown increased expression of the integrin-3 receptor subunit, which correlates with more rapid tumour progression and metastasis through advanced migration, invasion and proliferation. The influence of perioperative medication and postoperative pain management remains unclear. To investigate the effects of ketamine, s-ketamine and MK 801 on integrin beta-3-mediated cell migration in pancreatic cancer cells in vitro. Methods: The effects of ketamine, s-ketamine and MK 801 on integrin beta-3 expression were investigated with immunoblot. Cell migratory potentials were analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semipermeable membrane under different stimuli. Results: Stimulation with ketamine and MK 801 significantly promoted migration in pancreatic cancer cells, increasing the expression of integrin beta-3. Conclusion: Novel therapeutic approaches target the effective modulation of specific signalling and transcription pathways. The prerequisite for such 'target therapies' is comprehensive knowledge about the respective carcinogenesis. Further studies are required to identify the underlying disease mechanisms of pancreatic carcinoma.

Mechanical ventilation of patients in helicopter emergency medical service transport: an international survey.

BACKGROUND: Mechanical ventilation in helicopter emergency medical service (HEMS) environments is a procedure which carries a significant risk of complications. Limited data on the quality and performance of mechanical ventilation in HEMS are available in the literature. METHOD: We conducted an international survey to evaluate mechanical ventilation infrastructure in HEMS and collect data of transported ventilated patients. From June 20-22, 2019, the participating HEMS bases were asked to provide data via a web-based platform. Vital parameters and ventilation settings of the patients at first patient contact and at handover were compared using non-parametric statistical tests. RESULTS: Out of 215 invited HEMS bases, 53 responded. Respondents were from Germany, Denmark, United Kingdom, Luxembourg, Austria and Switzerland. Of the HEMS bases, all teams were physician staffed, mainly anesthesiologists (79%), the majority were board certified (92.5%) and trained in intensive care medicine (89%) and had a median (range) experience in HEMS of 9 (0-25) years. HEMS may provide a high level of expertise in mechanical ventilation whereas the majority of ventilators are able to provide pressure controlled ventilation and continuous positive airway pressure modes (77%). Data of 30 ventilated patients with a median (range) age of 54 (21-100) years and 53% male gender were analyzed. Of these, 24 were primary missions and 6 interfacility transports. At handover, oxygen saturation (p < 0.01) and positive end-expiratory pressure (p = 0.04) of the patients were significantly higher compared to first patient contact. CONCLUSION: In this survey, the management of ventilated HEMS-patients was not associated with ventilation related serious adverse events. Patient conditions, training of medical crew and different technical and environmental resources are likely to influence management. Further studies are necessary to assess safety and process quality of mechanical ventilation in HEMS. TRIAL REGISTRATION: The survey was prospectively registered at Research Registry ( researchregistry2925 ).