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BackgroundThere is a need to support the diagnosis of anaphylaxis by objective markers. miRNAs are promising noncoding RNA species that may serve as serological biomarkers, but their use in diagnosing anaphylaxis has not been systematically studied to our knowledge. We aimed to comprehensively investigate serum biomarker profiles (proteins, lipids, and miRNAs) to support the diagnosis of anaphylaxis.MethodsAdult patients admitted to the emergency room with a diagnosis of anaphylaxis (3 hours) were included. Blood samples were taken upon emergency room arrival and 1 month later.ResultsNext-generation sequencing of 18 samples (6 patients with anaphylaxis in both acute and nonacute condition, for 12 total samples, and 6 healthy controls) identified hsa-miR-451a to be elevated during anaphylaxis, which was verified by quantitative real-time PCR in the remaining cohort. The random forest classifier enabled us to classify anaphylaxis with high accuracy using a composite model. We identified tryptase, 9α,11β-PGF2, apolipoprotein A1, and hsa-miR-451a as serological biomarkers of anaphylaxis. These predictors qualified as serological biomarkers individually but performed better in combination.ConclusionUnexpectedly, hsa-miR-451a was identified as the most relevant biomarker in our data set. We were also able to distinguish between patients with a history of anaphylaxis and healthy individuals with higher accuracy than any other available model. Future studies will need to verify miRNA biomarker utility in real-life clinical settings.FundingThis work is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) as part of the clinical research unit (CRU339): Food Allergy and Tolerance (FOOD@) (project number 409525714) and a grant to MW (Wo541-16-2, project number 264921598), as well as by FOOD@ project numbers 428094283 and 428447634.

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged >= 65 (elderly) in comparison to data from adults (18-64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001). Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome.

Zur Verringerung der Häufigkeit und Intensität von anaphylaktischen Ereignissen sind vorbeugende Maßnahmen wichtig, um allergische Patienten optimal zu versorgen. Bestimmte Faktoren können eine schwere Anaphylaxie nicht nur auslösen, sondern auch verstärken und sollten daher erkannt werden. Deswegen ist die Identifizierung und Priorisierung von Faktoren, die zu einem erhöhten Risiko für eine schwere Anaphylaxie führen sind sehr wichtig. In der vorliegenden Arbeit haben wir die Daten aus dem Anaphylaxie-Register (von 122 Zentren aus 11 europäischen Ländern) in logistischen Regressionsmodellen unter Berücksichtigung bestehender Schweregrade, Auslöser und Symptome analysiert, um das relative Risiko von Faktoren auf die Schwere der Anaphylaxie zu identifizieren. Höheres Alter und eine begleitende Mastozytose (OR: 3,1, KI: 2,6 - 3,7) zeigten sich als die wichtigsten Prädiktoren für ein erhöhtes Risiko einer schweren Anaphylaxie. Auch intensive körperliche Aktivität (OR: 1,5, CI: 1,3 - 1,7), männliches Geschlecht (OR: 1,2, CI: 1,1 - 1,3) und psychische Belastung (OR: 1,4, CI: 1,2 - 1,6) waren häufiger mit schweren Reaktionen verbunden. Zusätzlich wurden die Einnahme von Betablockern (OR: 1,9, CI: 1,5-2,2) oder ACE-Inhibitoren (OR: 1,28, CI: 1,05, 1,51) in zeitlicher Nähe zur Allergenexposition als wichtige Faktoren in der logistischen Regressionsanalyse identifiziert. Die Analyse, zeigt welche endogene und exogene Faktoren den Schweregrad eine Anaphylaxie beeinflussen können. Dies ermöglicht Patienten zu identifizieren, die aufgrund ihres relativ höheren Risikos für eine schwere Anaphylaxie verstärkte präventive Maßnahmen benötigen., Preventive measures to reduce the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or exacerbate the severity of anaphylaxis and therefore need to be recognized. Therefore, the identification and prioritization of factors associated with an increased risk of severe anaphylaxis is very important. In this work, we analyzed data from the anaphylactic registry (from 122 centers in 11 European countries) in logistic regression models, taking into account existing severity, triggers, and symptoms, to identify the relative risk of factors on the severity of anaphylaxis. Older age and concomitant mastocytosis (OR: 3.1, CI: 2.6 to 3.7) were found to be the most important predictors of increased risk of severe anaphylaxis. Also intense physical activity (OR: 1.5, CI: 1.3 - 1.7), male gender (OR: 1.2, CI: 1.1 - 1.3) and mental stress (OR: 1.4, CI: 1.2-1.6) were more frequently associated with severe reactions. In addition, the intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE inhibitors (OR: 1.28, CI: 1.05, 1.51) were identified as important factors in logistic regression analysis. Our data suggest that it may be possible to identify patients who, due to their relatively higher risk of severe anaphylaxis, require enhanced preventive measures.

Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances-requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases.

Presentation during European Academy of Dermato Venerology in Prague during The European Society of Laser Dermatology session.

NPWT is effective method in treatment of the open abdomen, but the opinions on the economic results are still inconclusive. The aim of the study was to evaluate the clinical and economic effects of the NPWT in patients treated of the open abdomen compared to standard treatment. The time of the NPWT introduction was also analysed (early vs delayed). The data of the patients treated inyears 2009-2012 including: clinical data, results of treatment, mortality, complications, number of surgical procedures, total cost of therapy were calculated.Mortality occurred in 9 patients with standard treatment (45%) and in 3 patients with NPWT treatment (18%). The length of hospital stay, intensive care stay, f requency of the complications, duration of antibiotic therapy, delayed fascia closure were higher in group with standard therapy. The mean cost of treatment of the patients treated withstandard therapy was 17.400 EUR/patient and 1.739,00 EUR/patient in NPWT group. Better clinical results and lower costs of treatment were observed in patients with early beginning of the NPWT (during 5 first days). NPWT is effective, safe and economically viable method in the open abdomen therapy. Early beginning of the NPWT treatment improve the results of treatment and reduce its cost.