Butyrate, Valerate, and Niacin Ameliorate Anaphylaxis by Suppressing IgE-Dependent Mast Cell Activation: Roles of GPR109A, PGE2, and Epigenetic Regulation.

Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during the fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate the development and function of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) remain unclear. In the current study, we analyzed the function and gene expression of mouse MCs in the presence of SCFAs in vitro and in vivo. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis and passive cutaneous anaphylaxis in mice. The majority of SCFAs, particularly propionate, butyrate, valerate, and isovalerate, suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by the Gi protein inhibitor pertussis toxin and by the knockdown of Gpr109a. A treatment with the HDAC inhibitor trichostatin A also suppressed IgE-mediated MC activation and reduced the surface expression level of FcεRI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly reduced by PGE2 but not by PGD2. Furthermore, SCFAs enhanced PGE2 release from stimulated MCs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist, but not by an EP4 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by cyclooxygenase inhibitors and the EP3 antagonist. We conclude that SCFAs suppress IgE-mediated activation of MCs in vivo and in vitro involving GPR109A, PGE2, and epigenetic regulation.

A practical guide for implementing omalizumab therapy for food allergy.

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.

Management of Refractory Anaphylaxis: An Overview of Current Guidelines.

In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor-acetyl hydrolase or hereditary alpha-tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.

Prehospital and In-Hospital Treatment with Adrenaline and Related Prognosis in Anaphylaxis Patients.

INTRODUCTION: Although intramuscular adrenaline is the recommended first-line treatment for anaphylaxis, not all patients receive this treatment. The consequences in daily clinical practice are sparsely described. This study aimed to investigate the treatment administered to anaphylactic patients and the related prognosis. METHODS: A retrospective register-based study of patients with anaphylaxis referred to the allergy centre, Odense University Hospital (2019-2021). Each patient's medical records were reviewed for contacts with the emergency departments and the prehospital emergency medical service in the Region of Southern Denmark. The World Allergy Organization (WAO) grading system was used to assess the severity of prehospital and in-hospital anaphylaxis. Furthermore, the treatment administered to the patients was registered. RESULTS: In total, 315 patients were included. The prehospital system had contact with 256 of these patients (two were released prehospitally following treatment and 12 patients had insufficient data to assess anaphylaxis). Of the remaining 242 patients, 115 had anaphylaxis prehospitally (WAO grades 3-5); 59% (67/115) received adrenaline. Among the 67 patients who received prehospital adrenaline, 9 patients (13.4%; 95% CI: 6.3-24.0%) still had anaphylaxis at arrival at the emergency department. Of the 48 patients that were not treated with prehospital adrenaline, 17 patients (35.5%; 95% CI: 22.1-50.5) had anaphylaxis at the arrival to the emergency department. Among the 127 patients without prehospital anaphylaxis (WAO grades 0-2), 22 patients (18.2%; 95% CI: 11.8-26.2%) who did not receive prehospital adrenaline had anaphylaxis at arrival to the emergency department, while none of the 6 patients treated prehospitally with adrenaline had anaphylaxis. CONCLUSION: Omission of prehospital adrenaline in anaphylactic patients is associated with more severe anaphylactic symptoms at arrival to the hospital. Adrenaline treatment remains suboptimal since only half of the patients received prehospital adrenaline and only 1 out of 4 patients, with clinical signs of anaphylaxis, received adrenaline inside the hospital.

Prevention of Anaphylaxis Episodes in Idiopathic Anaphylaxis by Omalizumab.

INTRODUCTION: In 15-35 percent of patients with anaphylaxis, the triggering allergen cannot be found; therefore, a diagnosis of idiopathic anaphylaxis (IA) is made. We report on the outcomes in patients with IA treated with omalizumab. METHODS: We included consequent omalizumab-treated IA adult patients treated with omalizumab 300 mg every 4 weeks. RESULTS: Out of 7 patients, 6 were female, median age 40 years with the frequency of anaphylaxis episodes from 3 in 2 years to 5 in 4 months. Baseline tryptase ranged from 1.71 to 12.0 µg/L. An increase in tryptase during anaphylaxis was documented in 6 patients. Activating KIT p.D816V variant was detected in 2 patients. One patient also had hereditary alpha-tryptasemia (HαT). The duration of omalizumab treatment was 0.5-7.5 years. None of the patients have experienced an anaphylactic reaction since the start of treatment. Mild systemic reactions were reported in 6 patients (86%). The presence of underlying cMCD had no impact on the treatment outcome. CONCLUSION: All patients in our study had complete responses to omalizumab. The presence of KIT p.D816V and HαT did not influence the response to omalizumab treatment.

Revisiting dexamethasone use in the pediatric emergency department.

PURPOSE OF REVIEW: Dexamethasone is an essential treatment for common pediatric inflammatory, airway, and respiratory conditions. We aim to provide up-to-date recommendations for treatment of anaphylaxis, croup, coronavirus disease, multisystem inflammatory syndrome in children, and asthma with dexamethasone for use in the pediatric emergency department. RECENT FINDINGS: Literature largely continues to support the use of dexamethasone in most of the above conditions, however, recommendations for dosing and duration are evolving. SUMMARY: The findings discussed in this review will enable pediatric emergency medicine providers to use dexamethasone effectively as treatment of common pediatric conditions and minimize the occurrence of side-effects caused by gratuitous corticosteroid use.

Physician adherence to anaphylaxis guidelines among different age groups in emergency departments: 20-Year observational study.

BACKGROUND: Anaphylaxis is an acute and serious allergic reaction. Little is known about physician adherence to anaphylaxis guidelines among patients across different age groups. OBJECTIVE: To investigate real-world physician adherence to anaphylaxis guidelines among children, adults, and older adults in emergency departments. METHODS: This study retrospectively analyzed all consecutive patients with anaphylaxis who presented to 2 emergency departments at 2 branches of the largest tertiary hospital in Taiwan, between 2001 and 2020. Patients who met the diagnostic criteria for anaphylaxis were enrolled and grouped by age: children (<18 years), adults (18-64 years), and older adults (≥65 years). RESULTS: We enrolled 771 patients with anaphylaxis (159 children, 498 adults, and 114 older adults). Intramuscular epinephrine was administered in 294 cases (38.1%). There was a significant age-group difference in the rate of intramuscular epinephrine administration (46.5% in children, 37.3% in adults, and 29.8% in older adults; P trend = .004). When stratified by severity, 14.3% of older adults with moderate reactions received intramuscular epinephrine, whereas 35.2% of adults and 55.3% of children received intramuscular epinephrine (P trend < .001), whereas such difference was not found in patients with severe reactions. Upon discharge from emergency departments, 15.3% received allergist referral (52.2% in children, 6.6% in adults, and 1.8% in older adults; P trend < .001); 12.5% received education on avoidance of triggers (18.9%, 11.4%, and 7.9%; P trend = .01), and 16.1% received education on alarm symptoms (21.4%, 15.1%, and 13.2%; P trend = .05). CONCLUSION: The real-world physician adherence to anaphylaxis guidelines remains suboptimal in emergency departments, particularly among older adults. Physician continuing education is needed to improve the gap between anaphylaxis guidelines and clinical practice.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Frequencies and predictors of subcutaneous and intraosseous injection with 4 epinephrine autoinjector devices.

BACKGROUND: To prevent anaphylaxis-associated illness, intramuscular epinephrine injection is recommended. Subcutaneous injection may reduce efficacy, and intraosseous injection promotes morbidity. A few studies suggested that commercially available thigh epinephrine autoinjectors (EAIs) may induce subcutaneous/intraosseous injection in some adults. OBJECTIVE: To estimate the subcutaneous/intraosseous-injection rates of 4 EAIs by comparing their needle lengths with the ultrasound-measured skin-to-muscle depth and skin-to-bone depth of the midthigh of adults with allergic diseases in a cross-sectional study and to determine patient factors that predict subcutaneous EAI injection. METHODS: Thigh ultrasound was conducted in a convenience-recruited cohort with minimal and maximal compression to estimate the effect of EAI-induced compression. Subcutaneous/intraosseous-injection rates were estimated for Anapen (BioProject), EpiPen (Mylan), Jext (ALK), and Emerade (Medeca). Multivariate analyses for subcutaneous-injection risk were conducted with age, male/female sex, abdominal and thigh circumferences, and upper-arm skinfold thickness. RESULTS: A total of 68 patients were recruited. Compression thinned the subcutaneous tissue and muscle by 1 and 9 mm, respectively, on average. Projected subcutaneous-injection rates with/without compression were high for Anapen (65%-66%), moderate for EpiPen and Jext (29%-38%), and lowest for Emerade (13%-21%). Compression introduced a small intraosseous-injection risk with Emerade (4%). Female sex predicted subcutaneous injection (odds ratio, 1.3-2.0; all P < .001). Depending on the EAI, 29% to 97% of women and 0% to 41% of men would be injected subcutaneously. Older men were at risk of intraosseous Emerade injection. Obesity-related variables predicted subcutaneous injection poorly. CONCLUSION: Anapen was associated with high subcutaneous-injection rates. EpiPen and Jext were projected to provide intramuscular injection in all men without risk of intraosseous injection. Emerade yielded the lowest subcutaneous-injection rates in women. Compression largely affected the muscle. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02886468.

Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Mast Cell-Targeting Therapies in Mast Cell Activation Syndromes.

PURPOSE OF REVIEW: Provide an overview of the expanding landscape of mast cell (MC)-targeting treatments in mast cell activation syndromes (MCAS). RECENT FINDINGS: Tyrosine-kinase inhibitors (TKIs) targeting wild-type and mutated KIT can efficiently induce MC depletion. Avapritinib and midostaurin can also temper IgE-mediated degranulation. Avapritinib has been recently approved by the FDA for the treatment of indolent systemic mastocytosis (ISM). Targeting activation pathways and inhibitory receptors is a promising therapeutic frontier. Recently, the anti Siglec-8 antibody lirentelimab showed promising results in ISM. MCAS is a heterogeneous disorder demanding a personalized therapeutic approach and, especially when presenting as anaphylaxis, has not been formally captured as outcome in prospective clinical trials with TKI. Long-term safety of TKI needs to be addressed. New drugs under investigation in diseases in which non-neoplastic MCs play a pivotal role can provide important inputs to identify new efficient and safe treatments for MCAS.

The confidence and competence of primary school staff to administer an adrenaline auto-injector.

School teachers are often inadequately prepared to use an adrenaline auto-injector (AAI), resulting in potentially dangerous treatment delays. The purpose of this study was to assess the observed competence, and self-reported confidence, of primary school teachers in the Republic of Ireland (RoI) to use an AAI. An evaluation of whether there was a link between confidence and competence was also assessed. Teachers from four primary schools in the RoI completed a questionnaire to assess their prior level of experience, training, and confidence levels with AAI administration. The four steps in administrating trainer AAI to a mannequin simulator were then assessed. A total of 61 teachers participated (out of a population of 80). The mean self-reported confidence was 1.82 out of 5 (SD = 0.96). There was no significant difference in confidence between trained and untrained participants (U = 240.5, NS). Participants who had received AAI administration training performed significantly more of the steps correctly (mean = 3.85, SD = 0.95) as compared to those who had received no training (mean = 2.97, SD = 1.10; U = 180.5, p = 0.008). There was no correlation between confidence in administrating AAI and the percentage of steps in the procedure performed correctly (rho = -0.17, NS).  Conclusion: Improvements in readiness to administer AAIs can be achieved through the application of more effective approaches to teaching clinical skills, changes to school policies and practices, and consideration of the design of AAIs in order to make their operation safer and simpler. It is important that teachers have the confidence and competence to safely administer an AAI. What is Known: • Poor ability in adrenaline auto-injector use seen across population groups-healthcare professionals, patients, carers, and school staff • Training in the use of adrenaline auto-injectors has positive impact on competency What is New: • Irish school teachers show poor levels of competency in adrenaline auto-injector use • No observed correlation between reported confidence and competency.

Health disparities in hymenoptera venom allergy management.

Background: Hymenoptera venom anaphylaxis (HVA) is reported in up to 3% of stings and accounts for approximately 40 US deaths annually. HVA patients require immediate availability of epinephrine and Allergist referrals for consideration of venom immunotherapy. Data regarding epinephrine autoinjector prescriptions, Allergist referral rates, and potential racial disparities are limited. Objective: The primary objective was to determine if there were statistically significant differences in epinephrine autoinjector prescriptions and Allergist referrals between white and African American patients. The secondary objectives were to determine if there were statistically significant differences between adult and pediatric patients and to determine if there were significant differences between epinephrine prescriptions between patients with and without Allergist referrals. Method: This study is a retrospective, descriptive chart review analyzing patients seen between January 01, 2019 and December 31, 2021. Data were obtained utilizing the Epic Systems (Verona, WI) application Slicer Dicer. Individual chart review was performed for age, race, epinephrine autoinjector prescription, and Allergist referral. Results: 342 patients were identified as having HVA. White patients (60 out of 219; 27.4%) were more likely to get epinephrine autoinjector prescriptions than African American patients (17 out of 109; 15.6%) (p = 0.018). Adult patients (25 out of 314; 8.0%) were less likely than pediatric patients (8 out of 28; 28.6%) to have Allergist referrals (p = 0.004). Patients with Allergist referrals (25 out of 32; 78.1%) were more likely to be prescribed an epinephrine autoinjector than patient without Allergist referrals (54 out of 310; 17.4%) (p < 0.00001). Conclusion: Epinephrine autoinjector prescriptions and Allergist referrals are low overall in HVA. Racial disparities were identified with African American patients being significantly less likely to receive epinephrine autoinjector prescriptions. Additionally, adult patients, who may be at increased risk, were less likely to receive Allergist referrals.

Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

A retrospective audit of adult and paediatric anaphylaxis management from two Australian metropolitan mixed emergency departments.

BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction, with presentations to emergency departments (EDs) increasing across Australia. Understanding the features of those presenting with anaphylaxis and aspects related to its optimal clinical management across the admission, treatment and discharge settings is needed to minimise its impact. We aimed to evaluate the nature and management of presentations related to anaphylaxis across two Australian EDs. METHODS: Retrospective audit of paediatric and adult patients presenting to a community or tertiary level ED with anaphylaxis from 1 May 2018 to 30 April 2019. Data extracted from medical records included demographic characteristics, causative agents, clinical features, treatments administered across community, ambulance or ED settings, as well as post-discharge care arrangements including provision of Adrenaline Auto-Injector (AAI) and Allergy/Anaphylaxis Action Plan (AAP). RESULTS: A total of 369 (107 paediatric and 262 adult) ED presentations were identified. A total of 94 (36%) adult and 46 (43%) paediatric patients received pre-hospital adrenaline, with a further 91 (35%) adult and 29 (27%) paediatric patients receiving a dose of adrenaline in the ED. The most commonly administered treatment in ED were corticosteroids, given to 157 (60%) adult and 55 (51%) paediatric patients. Among those requiring an AAI for discharge, 123/210 (59%) adult and 57/91 (63%) of paediatric patients left hospital with an AAI. In contrast, among those requiring an allergy/anaphylaxis action plan (AAP) on discharge, 61/206 (30%) adult and 30/90 (33%) of paediatric patients left hospital with one. Factors associated with an increased likelihood of receiving AAI on discharge in paediatric and adult patients included receipt of any adrenaline, receipt of two or more doses of adrenaline, and longer duration of hospital stay. Adults presenting within business hours were more likely to be discharged with AAI, but no such difference was observed for paediatric patients. Similar findings were evident for provision of AAP on discharge. CONCLUSION: These findings demonstrate the need to improve assessment and treatment in the ED. In particular, the observed large variability in provision of AAI and AAP on discharge presents opportunities to explore strategies to improve awareness and provision of these critical components of post-discharge care.

NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock.

Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients' hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute heart failure might improve AS therapy. Ovalbumin-sensitized rats were randomly allocated to six groups: control (CON), shock (AS), shock treated with NButGT alone before (AS+pre-Nbut) or after (AS+post-Nbut) AS onset, shock treated with epinephrine alone (AS+EPI) and shock group treated with combination of epinephrine and NButGT (AS+EPI+preNBut). Induction of shock was performed with an intravenous (IV) ovalbumin. Cardiac protein and cycling enzymes O-GlcNAcylation levels, mean arterial pressure (MAP), heart rate, cardiac output (CO), left ventricle shortening fraction (LVSF), mitochondrial respiration, and lactatemia were evaluated using Western blotting experiments, invasive arterial monitoring, echocardiography, mitochondrial oximetry and arterial blood samples. AS decreased MAP (-77%, p < 0.001), CO (-90%, p < 0.001) and LVSF (-30%, p < 0.05). Epinephrine improved these parameters and, in particular, rats did not die in 15 min. But, cardiac mitochondrial respiration remained impaired (complexes I + II -29%, p < 0.05 and II -40%, p < 0.001) with hyperlactatemia. NButGT pretreatment (AS+pre-Nbut) efficiently increased cardiac O-GlcNAcylation level as compared to the AS+post-Nbut group. Compared to epinephrine alone, the adjunction of NButGT significantly improved CO, LVSF and mitochondrial respiration. MAP was not significantly increased but lactatemia decreased more markedly. Pretreatment with NButGT increases O-GlcNAcylation of cardiac proteins and has an additive effect on epinephrine, improving cardiac output and mitochondrial respiration and decreasing blood lactate levels. This new therapy might be useful when the risk of AS cannot be avoided.

[Prehospital care of anaphylactic reactions by the air rescue and ground-based emergency services Dresden : An analysis of treatment and outcome]. / Präklinische Versorgung von anaphylaktischen Reaktionen durch die Dresdner Luft- und Bodenrettung : Analyse von Therapie und Outcome.

BACKGROUND: Anaphylaxis can lead to a life-threatening situation. Therefore, rapid diagnosis and emergency treatment is indicated. Immediate treatment with intramuscular adrenaline (or intravascularly with sufficient medical expertise) in anaphylaxis with cardiovascular and/or respiratory symptoms is recommended by various guidelines. Previous studies have shown that anaphylaxis is often not treated according to guidelines and that adrenaline in particular is rarely administered. OBJECTIVE: The aim of the study was to investigate the data on emergency treatment and outcomes of patients with anaphylaxis by the air rescue and ground-based emergency services Dresden. Moreover, the results of the air- and ground-based services were compared. The focus was on administration of adrenaline and outcomes. MATERIALS AND METHODS: Data from the ground-based emergency service Dresden (from 2012 to 2016) and the air rescue service Dresden (from 2008 to 2015) related to anaphylactic reactions were analyzed retrospectively. The severity of the anaphylaxis, the emergency medication administered, further monitoring, and outcomes were analyzed. RESULTS: Data from 152 adults/29 children were analyzed for air rescue and 1131 adults/223 children for the ground-based emergency service. Adults with grade II-IV anaphylaxis received adrenaline in 19% (air rescue) and 7% (ground rescue) of cases. Children with grade II-IV anaphylaxis received adrenaline in 7% (air rescue) and 8% (ground rescue) of cases. Immediate drug therapy led to an improvement in general condition in 96-98% (air rescue) and 72-77% (ground-based emergency service) of cases. A significant correlation was found between the administration of adrenaline and the improvement in outcome in the ground-based emergency cohort. CONCLUSION: Guideline-compliant first-line therapy with adrenaline was not performed in the majority of the cases analyzed in this study. The significant effect of adrenaline on outcome demonstrated in this study emphases the need to improve the emergency treatment of anaphylactic reactions.

Remimazolam-Induced Anaphylaxis and Cardiovascular Collapse: A Narrative Systematic Review of Eleven Cases.

Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords 'remimazolam AND anaphylaxis' were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed.

[EPIPEN INSTRUCTIONS FOR ANAPHYLAXIS PATIENTS DURING DISPENSING: FACTORS RELATED TO THE QUALITY OF PHARMACISTS' INSTRUCTIONS].

BACKGROUND AND AIM: We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients. RESULTS: The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients. DISCUSSION: For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.

[TWO CASES OF LARYNGEAL EDEMA CAUSED BY SUBLINGUAL ALLERGEN IMMUNOTHERAPY].

Sublingual immunotherapy is a widely used treatment, and serious adverse reactions such as anaphylaxis are rare. We report two cases of laryngeal edema as adverse reactions to sublingual immunotherapy, which could be continued due to a change in the administration method. Case 1 presents a 15-year-old male suspected to have had anaphylaxis due to the dust at the age of 6 years. He started treatment with Miticure® and developed laryngeal edema 30 minutes after taking the 10000JAU dose on the 10th day. laryngeal edema was treated with intravenous infusion. Case 2 presents a 48-year-old woman. She started treatment with Cidacure® and developed respiratory distress and laryngeal edema 1 hour after taking the 5000JAU dose on the 5th day. she had resolved mildly without therapeutic intervention. In both cases, the patients were switched to sublingual spitting, resumed with the initial dose cautiously, and were able to continue. Sublingual immunotherapy is a safe treatment, but sudden adverse reactions may occur. Laryngeal symptoms may be treated by changing to the sublingual spitting method, but laryngeal findings should be examined, and the dosage should be carefully increased.