Health registries improve our knowledge, support optimising care organisation and quality, and support the implementation of personalised medicine. While many registries collect data in the field of allergy and immunology worldwide, only few registries are dedicated to anaphylaxis. Despite a growing scientific interest in anaphylaxis over the past decade, current knowledge on severe anaphylaxis is insufficient, with many unresolved questions regarding risk factors, impact of cofactors, specific aspects in childhood, details related to trigger and the most appropriate therapeutic strategies. There is a clear need for health registries dedicated to severe anaphylaxis to address these gaps. This article aims first to present the rationale for creating a new registry dedicated to severe anaphylaxis by defining and describing health registries and related challenges in the field of anaphylaxis worldwide and in France, identifying knowledge gaps in severe anaphylaxis, and second to present the objectives of the new French anaphylaxis registry, named Severe Anaphylaxis in France nEtwork (SAFE). In 2026, the French professional council for allergy, in partnership with key allergy stakeholders in France, notably the Société française d'allergologie (the French allergy society), will inaugurate the SAFE registry in order to provide inputs on severe anaphylaxis, integrating all involved caregivers, including emergency care, anaesthesia and intensive care, paediatrics, research structures and patient associations.

Background:Our study aims to describe the French heart-lung graft allocation system, to compare it with allocation systems used in other countries, and to explore potential solutions to improve access to this rare transplantation procedure. Methods:Our study integrates published literature and multidisciplinary expert opinions to examine heart-lung graft allocation in France. Results:The heart-lung transplantation (HLTx) programme was initiated in France in 1987. The number of procedures then increased steadily until the 2010s. Improved knowledge on right ventricular function recovery after double lung transplantation (LTx) for pulmonary hypertension combined with the organ shortage then led to a sharp drop in the number of HLTx recipients worldwide. In France, the number of HLTx procedures is only about ten per year and the main indication is Eisenmenger syndrome. Most HLTx candidates in France receive grafts only if they are in the high-urgency category highlighting the difficulty of access to heart-lung transplants. A re-appraisal of graft allocation rules thus seems mandatory to allow graft access to patients who do not meet high-urgency criteria and whose better general health predicts better post-HLTx outcomes. Conclusions:As HLTx candidates in France are placed on the heart-transplant list in competition with heart-only transplant candidate, one option would be to reconsider the heart score assigned to HLTx candidates upon listing.

BACKGROUND:Liberation from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) remains challenging. To date, there is limited evidence from observational studies supporting pharmacologic interventions to facilitate successful VA-ECMO weaning. The current study aimed to evaluate the efficacy and safety of a single dose of levosimendan in patients supported by VA-ECMO who met predefined criteria for weaning. METHODS:The WEANILEVO study was a multicenter, double-blind, randomized, parallel-group, placebo-controlled trial. Eighty patients from five French centers who met VA-ECMO weaning criteria were randomly assigned 1:1 to receive either levosimendan (0.2 μg · kg -1 · min -1 ) or placebo for 24 h. The primary endpoint was VA-ECMO weaning failure, defined as absence of weaning within 48 h, recourse to another circulatory assistance device, or death within 7 days of weaning. RESULTS:Due to halted funding, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 80 patients (40 in the levosimendan group and 40 in the control group). VA-ECMO weaning failure occurred in 25% of patients in both the levosimendan and placebo groups (odds ratio, 1.00 [95% CI, 0.36 to 2.75]; P = 1.00). Acute kidney injury at day 30 was significantly more frequent in the levosimendan group (62.5% vs . 38.5%; odds ratio, 2.67 [95% CI, 1.08 to 6.62]; P = 0.03). Patients receiving levosimendan required more vasopressor support (47.5% vs . 28.2%; P = 0.07) and had longer intensive care unit stays (12 [7 to 24] vs . 6 [4 to 13] days; P = 0.02). Mortality rates at 30 days (18.0% vs . 33.3%; P = 0.07) and 1 yr (31.6% vs . 51.4%; P = 0.08) did not significantly differ between groups. CONCLUSIONS:Levosimendan administration did not reduce VA-ECMO weaning failure in patients who already met weaning criteria; however, a clinically important benefit or harm cannot be ruled out. The observed higher incidence of acute kidney injury and longer intensive care unit stays in the levosimendan group are hypothesis generating and require confirmation in larger, adequately powered trials.

Background: Perioperative immediate hypersensitivity reactions (POHRs) are potentially fatal complications of anesthesia. Although tryptase is a cornerstone biomarker for mast cell activation (MCA), its diagnostic limitations call for a better understanding of the underlying mechanisms and phenotypes of POHRs to guide management. Objective: Compare the phenotypes of patients who experience POHRs based on their MCA profiles using tryptase and histamine assays. Methods: This retrospective multicenter study included patients assessed by the GERAP Network who experienced POHRs from 2017 to 2024. Clinical characteristics and biomarker correlation were analyzed across MCA profiles. MCA profiles were determined based on the presence of MCA (peak tryptase >1.2×baseline tryptase+2 μg/L; NoMCA vs MCA) and a peak tryptase value (elevated if ≥8 μg/L; low tryptase [LT] vs high tryptase [HT]) or histamine release (elevated if ≥10 nmol/L). Results: MCA was recorded in 626 of the 930 patients (67%). HT-MCA and LT-NoMCA were the most frequent profiles, detected in 60% and 27% of patients, respectively. POHRs were more severe in the HT-MCA group than in the LT-NoMCA group (85% vs 43%; P<.0001). Skin test results were positive in 26% of patients in the LT-NoMCA group, and some patients exhibited histamine release only. The MCA profile differed depending on the drugs used during the perioperative period, indicating the involvement of various mechanisms. Conclusions: While most reactions involving high tryptase concentrations and MCA are consistent with an IgE-mediated mechanism, our results showed that identifying the underlying mechanism of POHRs with a high degree of certainty is still not possible using the tools currently applied in daily clinical practice.

OBJECTIVE:The French Society of Anaesthesia and Intensive Care (SFAR) and the French Society of Allergology (SFA) have collaborated to propose guidelines for the diagnosis and management of perioperative immediate hypersensitivity reactions (IHR). DESIGN:A group of 23 French experts from the SFAR and the SFA was assembled. Any potential conflicts of interest were officially declared at the outset of the recommendations development process, which was conducted independently of any industry funding. The authors used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to assess the level of evidence in the literature. METHODS:4 fields were defined: 1) Diagnostic assessment of perioperative IHR reactions; 2) Risk factors for perioperative IHR reactions; 3) Treatment in scheduled and emergency situations and; 4) Treatment of perioperative IHR reactions. For each field, the aim of the recommendations was to answer questions formulated by the experts according to the PICO model ("Population, Intervention, Comparison, Outcome"). Based on these questions, an extensive literature search covering the last 24 years was carried out using predefined keywords according to the PRISMA recommendations. The level of evidence was analysed using the GRADE method. The recommendations were formulated using the GRADE method, then voted on by all the experts using the GRADE grid method. RESULTS:The experts' summary work and the application of the GRADE method resulted in 70 recommendations concerning 31 questions. After 3 rounds of voting and several amendments, strong agreement was reached on 70 recommendations. Of these recommendations, 6 have a high level of evidence (6 GRADE 1), 16 have a low level of evidence (16 GRADE 2) and 48 are expert opinions. Finally, for 1 question, no recommendation could be made. CONCLUSION:There was strong agreement among the experts to formulate recommendations aimed at providing a benchmark for the diagnosis and management of perioperative IHR.

Infective endocarditis (IE) is an uncommon but life-threatening disease, most frequently caused by Staphylococcus aureus, streptococci, and enterococci. Vagococcus fluvialis is a Gram-stain positive coccus, phenotypically close to enterococci, and rarely identified in human infections due to diagnostic challenges. We present a case report of a patient with a prosthetic valve endocarditis caused by V. fluvialis, along with details of the treatment initiated in a 63-year-old man with a history of mitral valve bioprosthesis for prior IE. He presented with fever, confusion, asthenia, and myalgia. Echocardiography identified a large vegetation on the mitral prosthesis. Blood cultures grew V. fluvialis, confirmed by MALDI-TOF mass spectrometry and 16S RNA sequencing. Antibiotic therapy with intravenous amoxicillin led to rapid clinical and microbiological improvement. However, despite this favorable initial clinical response, follow-up echocardiography demonstrated progression of the vegetation, ultimately necessitating a redo mitral valve replacement on Day 20. Intraoperative findings confirmed extensive vegetation without paravalvular complications. Although the prosthesis cultures were negative, sequencing identified V. fluvialis again. Postoperative recovery was uneventful, and the patient was discharged in good condition. V. fluvialis is increasingly recognized in human infections but remains difficult to distinguish from enterococci using conventional methods. Accurate diagnosis requires advanced tools such as 16S RNA sequencing. Unlike previous cases, this prosthetic valve IE progressed more slowly, characterized by persistent vegetation rather than acute valve destruction. Successful management was achieved through amoxicillin therapy combined with surgical intervention. This case highlights V. fluvialis as a rare but emerging cause of IE, emphasizes the need for precise microbiological identification, and suggests that amoxicillin monotherapy may contribute to initial clinical stabilization. Further reports are required to specify V. fluvialis-related IE prognosis and to establish the most effective treatment.

Background: Biliary contamination significantly correlates with major comorbidities during pancreatic head resection. Recently, a piperacillin-tazobactam prophylaxis demonstrated a lower rate of infectious complications (IC) and postoperative pancreatic fistula (POPF) in this population. However, bacterial contamination is rare in patients without a preoperative biliary drainage (PBD) and probably could not benefit from this antibiotic. Furthermore, little is known about the role of biliary fungal contamination. Method: All retrospective cases undergoing pancreatic head resection with intraoperative biliary sample were included. Postoperative outcomes of patients with a piperacillin-tazobactam-based treatment were compared to cases in which a narrow-spectrum antibiotic was administrated, stratified according to the use of a PBD. The same analysis was repeated for antifungal treatment administration. Results: Among the 205 cases included, PBD was necessary in 127 patients (62%). Broad-spectrum treatment was associated with fewer overall and clinically relevant POPF (p = 0.001 and p = 0.004), overall morbidity (p = 0.044), and overall IC (p = 0.018), but only in the PBD group. Similarly, antifungal treatment was significantly associated with some specific IC only in the PBD group. At multivariable analysis, antifungal therapy in the whole cohort (p = 0.029) and the use of a piperacillin-tazobactam (p = 0.007) treatment in patients with a PBD were independently associated with a reduced risk of a clinically relevant POPF. Conclusions: A broad-spectrum antibiotic therapy reduces overall morbidity after pancreatic head resection, but only in cases with a history of PBD. Furthermore, the use of an antifungal prophylaxis or therapy should be further investigated in these patients because it may reduce the risk of some IC.

Since 1998, leuko-reduction is used in France for all platelet concentrates (PCs), apheresis-derived (APCs) and pooled whole blood-derived buffy-coats (BCPCs). Platelet additive solutions (PAS), introduced in 2005, accounted for over 80% of the platelet supply from 2011 to 2017. The Intercept pathogen reduction technology (PR), started in a pilot study in 2007, was generalized in 2018. Between 2007 and 2021, the use of BCPCs increased steadily from 23% to 70% of the supply. Objectives: to analyze the impact of these modifications on adverse transfusion reactions (ATRs), patient management and blood transfusion organization. Results: The overall incidence of ATRs /105 PCs is significantly lower with PAS- and PR-PCs as compared to PCs in plasma (PL), with the decreasing hierarchy PL > PAS > PR. PAS- and PR-PCs lead to significantly lower incidences of allergy and alloimmunization to RBC antigens (RC-AI) ATRs. The incidence of bacteria transmission (TTBI) is significantly reduced by 95% with PR-PCs. APC-related ATR incidence is significantly higher than BCPC for allergy (+233%), TTBI (+100%), APTR (+75%), Major-ABO-II (+65%), HLA/HPA-AI (+38%), FNHTR (+22%), and life-threatening ATRs (+106%). A single diagnosis is significantly less associated with APCs: RC-AI (-47%). The generalization of PR-PCs, which exhibit a lower platelet content than PAS- and PL-PCs, is associated with a significant 9% decrease in the ATR incidence per PC, a 13% increase in the number of PCs transfused per patient, and a nonsignificant 3% increase in the ATR incidence per patient. The outdated PCs percentage declined significantly from 3.7% to 1.7%.

BACKGROUND:The IMOTEC study aims to determine whether a point-of-care viscoelastic hemostatic assay (VHA)-guided algorithm is cost-effective for the management of ongoing bleeding. METHODS:Stepped wedge cluster randomized trial, patient blinded, conducted at 16 French academic cardiac surgery centers from 01/2017 to 02/2020. Adults undergoing elective or urgent cardiac surgery with ongoing bleeding were enrolled during 2 successive inclusion periods: 1) transfusion guided on standard hemostasis tests (control period), and 2) transfusion using a VHA-guided algorithm. The primary objective was to estimate the efficiency of VHA based on the 1-year incremental cost-utility ratio (ICUR, primary outcome). Secondary outcomes included transfusion, postoperative complications, duration of stay in-hospital, reintervention, and mortality. RESULTS:1095 patients were randomized, and 1044 (95.3%) were analyzed. The mean utility was 0.60 (±0.30) in the VHA vs. 0.61 (±0.30) in the control period, adjusted difference, -0.01 [95% CI, -0.09 to 0.07]. The ICUR did not suggest that the VHA-guided algorithm was cost-effective. One-year mortality was 12.0% for VHA and 10.9% for control, Hazard Ratio, 1.69 [95% CI, 0.98-2.89], P = .06. The frequency of plasma and platelet transfusions was significantly lower in the VHA compared to the control period (respectively, 48.8% vs. 72.4%, P < 0.0001 and 52.3% vs. 74.1%, P = .0002), whereas fibrinogen administration was more frequent in the VHA period (58.4% vs. 47.0%, P = .002). The median in-hospital length of stay was significantly shorter in the VHA vs. control period: 11.0 days (8.0-18.0) vs. 14.0 (9.0-22.0), P = .02. CONCLUSIONS:The ICUR did not suggest that VHA was cost-effective in cardiac surgery patients with ongoing bleeding, compared with standard tests. TRIAL REGISTRATION:Clinical trial submission: November 2, 2016 Registry name: Cost-Utility Analysis of Management of Peri Operative Hemorrhage Following Cardiac Surgery With Cardiopulmonary Bypass (IMOTEC) ClinicalTrials.gov Identifier: NCT02972684 URL registry: https://clinicaltrials.gov/study/NCT02972684.

Aim To study cardiac serious adverse reactions in blood donors (CSARD) reported in the context of whole blood donation (WBD) or apheresis donation (AD) in France. Although potentially serious, they have been poorly studied so far. Methods Retrospective descriptive study of the 125 CSARD (myocardial infarction-MI, acute coronary syndrome-ACS, angina pectoris-AP, rhythm disorder-RD) reported between 2010 and 2021. The studied parameters were age, gender, type of donation, diagnosis, time to onset, imputability, severity (grade), cardiovascular risk factors (CVRF). They were reviewed within the reports by 5 experts, who independently recorded their opinions on each parameter (except age, gender, type of donation). The collegial analysis of the opinions then resulted in a consensus for all cases. The time between the occurrence of CSARD and donation has been extended and limited to 48 h. An additional criterion of imputability was added for the CSARD attributed to causes other than the donation (e.g., coronary atheroma) but Aggravated or Triggered by the donation: AT1 possibly (>24–48 h post-donation), AT2 probably (>12–24 h post-donation) or AT3 certainly (within 12 h or pre-donation start). Results Out of 125 reports, 50 were excluded: cardiac qualification of SARD invalidated (8), lack of data (2), absence donation (1), occurrence more than 48 h after the donation (39). The 75 included CSARD (including 5 deaths) comprised 58 coronary events (38 MI, 13 ACS, 7 AP) and 17 RD, and their complementary imputability criterion (AT) was classified respectively as follows 1 (20%), 2 (24%), 3 (56%). The estimated cumulative incidence of CSARD/106 donations is 2.1, significantly higher for AD (5.3) than for WBD (1.6; p < 0.001). The male (M) and female (F) percentages are 81% vs 19%, significantly different from the ones of the standard donor population over 2010–21: 48% M vs 52% F. The median ages, 55 years (30–70) in men, and 47 years (23–68) in women, were significantly higher than the ones of standard donor population 2010–21, respectively 46 (p < 0,001) and 41 (p = 0,04). In the 58 coronary accidents, at least 3 CVRF were noted in 38 cases (66%) and at least 4 CVRF in 20 cases (34%), including 5 with 5 CVRF. In 6/75 cases (8%) pre-existing signs not detected during the pre-donation interview (PDI) would have permanently contraindicated donation. Conclusions A complementary study should assess whether a more formalised consideration of CVRF in the PDI could reduce the frequency of CSARD of coronary type.

OBJECTIVE:This study assessed the impact of intraoperative goal-directed fluid therapy integrated within an Enhanced Recovery After Surgery program on early coagulation parameters, transfusion requirements, hemoglobin levels, chest tube output, and hemodynamic profiles in patients undergoing elective cardiac surgery. METHODS:In this single-center, retrospective ancillary analysis, patients who underwent elective cardiac procedures between 2015 and 2021 were stratified based on the implementation of an Enhanced Recovery After Surgery protocol incorporating goal-directed fluid therapy. Propensity score matching generated 1026 well-balanced pairs. Primary end points included platelet count, fibrinogen concentration, prothrombin time, activated partial thromboplastin time, and hemoglobin levels measured at intensive care unit admission and on postoperative day 1. Secondary outcomes included transfusions (red blood cells, allogeneic blood components, coagulation factor concentrates), chest tube output, glomerular filtration rate, mean arterial pressure, central venous pressure, and vasoactive-inotropic score at intensive care unit admission and postoperative day 1. RESULTS:At intensive care unit admission, the Enhanced Recovery After Surgery group demonstrated significantly higher platelet count, fibrinogen, prothrombin time, and hemoglobin (all P < .001). Red blood cell transfusion rates were significantly lower intraoperatively and at postoperative day 1 (P < .001), whereas transfusion of other blood products and coagulation factor concentrates did not differ between groups. At postoperative day 1, the Enhanced Recovery After Surgery group exhibited significantly lower chest tube output (P < .001) and higher glomerular filtration rate (P = .042). Although mean arterial pressure remained comparable, central venous pressure was significantly lower and vasoactive-inotropic score was higher at intensive care unit admission in the Enhanced Recovery After Surgery group, with both parameters normalizing by postoperative day 1. CONCLUSIONS:Goal-directed fluid therapy within an Enhanced Recovery After Surgery program reduces intraoperative hemodilution, improves coagulation integrity, reduces postoperative bleeding, decreases transfusion needs, and maintains end-organ perfusion after elective cardiac surgery.

Background: Stress due to surgical trauma decreases postoperative lymphocyte counts (LCs), potentially favouring the occurrence of postoperative infections (PIs). Objectives: We aimed to determine whether postoperative lymphopaenia following thoracic or gastrointestinal cancer surgery is an independent risk factor for PIs and to identify modifiable factors related to anaesthesia and surgical procedures that might affect its occurrence. Study design: The EVALYMPH study was a prospective, multicentre cohort study with a 30-day patient follow-up. Multivariate analyses were performed to determine the risk factors for PIs and for postoperative lymphopaenia. Setting: Patients were included from January 2016 to September 2017 in 25 French centres. Patients: Adult patients admitted for thoracic or gastrointestinal cancer surgery were eligible for inclusion. Main outcome measure: PIs within 30 days after surgery were defined as urinary tract infections, pneumonia, surgical site infections and other infections (bloodstream infections or pleurisy). Results: Of 1207 patients included, 273 (22.6%) developed at least one infection within 30 days after surgery, with a median [IQR] time to onset of 8 [5 to 11] days. An increased risk of PI was significantly associated with an ASA score of IV: hazard ratio (HR) 4.27 (95% confidence interval (CI), 1.87 to 9.72), surgery > 200 min (HR 1.58 (1.15 to 2.17) and lymphopaenia on postoperative day 1 (POD1) (HR 1.56 (1.08 to 2.25). This risk was associated with changes in postoperative LC over time ( P = 0.001) but not with preoperative LC ( P = 0.536).POD1 lymphopenia was related to patient characteristics and duration of surgery but not to potentially modifiable other surgical or anaesthetics factors. Conclusions: POD1 lymphopaenia was associated with PIs in patients undergoing thoracic or gastrointestinal cancer surgery. To individualise care, patient characteristics and surgery duration should be taken into account.

Fibrinogen concentrate may reduce allogeneic blood product transfusion in cardiac surgery patients with bleeding associated with acquired hypofibrinogenemia. The European Society of Anaesthesiology and Intensive Care (ESAIC) has issued guidelines, but compliance to these guidelines has not been studied yet. This multicentre observational cohort study was aimed at evaluating the compliance of fibrinogen prescription with ESAIC. Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 13 French cardiac surgery centres were recruited from March 2017 to April 2018. Compliance with ESAIC guidelines was considered whenever patients received fibrinogen in case of hypofibrinogenemia and clinically relevant bleeding, or when patients did not receive fibrinogen concentrate if there was no hypofibrinogenemia and/or no clinically relevant bleeding. The primary endpoint was the percentage of patients who complied those guidelines. Secondary endpoints were to assess the consequences of non-compliance on in-hospital deaths and hospital length-of-stay. Among 2,649 adult patients undergoing cardiac surgery with cardiopulmonary bypass, 374 (14.1

BACKGROUND:Ensuring transfusion safety remains a major challenge. Pathogen-reduction technologies (PRT), such as the INTERCEPT™ Blood System (IBS), use amotosalen (a psoralen) as intercalating agent in nucleic acids and ultraviolet A (UV-A) light to block pathogen replication, reducing the risk of transfusion-transmitted infections. While IBS is approved for platelet concentrate (PC) treatment, its clinical impact on platelet function remains debated. In November 2017, IBS was implemented across all French blood banks (Établissement Français du Sang, EFS) for PCs. MATERIALS AND METHODS:We conducted a retrospective "before-after" study to evaluate the impact of PRT on platelet transfusion and clinical bleeding in cardiac surgery. The pre-PRT period was from January 2016 to June 2017, and the post-PRT period from January 2018 to June 2019. The study included adult patients who received PCs during or within two days after cardiac surgery in two teaching hospitals (Nancy and Reims). Patients with heart transplantation or requiring mechanical circulatory support were excluded. RESULTS:A total of 357 (Nancy) and 314 (Reims) patients were included, with no changes in anticoagulation, antiplatelet therapy, or surgical procedures. Platelet transfusion amount significantly decreased post-PRT (from 0.64 [0.54-0.81] to 0.57 [0.49-0.75] ×1011/10 kg; p<0.01), while transfusion of other blood products remained unchanged. Postoperative outcomes, including mediastinal drainage, reoperation for bleeding, ICU stay, and overall hospital stay, were also unchanged. DISCUSSION:The implementation of PRT using IBS did not impair the hemostatic properties of transfused platelets during cardiac surgery. Platelet and other blood product use, as well as clinical outcomes, were similar before and after PRT introduction. IBS-treated PCs are thus comparable to standard PCs in managing bleeding in cardiac surgery.

Anaphylaxis, an allergic reaction caused by the massive release of active mediators, can lead to anaphylactic shock (AS), the most severe and potentially life-threatening form of anaphylactic reaction. Nevertheless, understanding of its pathophysiology to support new therapies still needs to be improved. We performed a systematic review, assessing the role and the complex cellular interplay of mitochondria and oxidative stress during anaphylaxis, mast cell metabolism and degranulation. After presenting the main characteristics of anaphylaxis, the oxidant/antioxidant balance and mitochondrial functions, we focused this review on the involvement of mitochondria and oxidative stress in anaphylaxis. Then, we discussed the role of oxidative stress and mitochondria following mast cell stimulation by allergens, leading to degranulation, in order to further elucidate mechanistic pathways. Finally, we considered potential therapeutic interventions implementing these findings for the treatment of anaphylaxis. Experimental studies evaluated mainly cardiomyocyte metabolism during AS. Cardiac dysfunction was associated with left ventricle mitochondrial impairment and lipid peroxidation. Studies evaluating in vitro mast cell degranulation, following Immunoglobulin E (IgE) or non-IgE stimulation, revealed that mitochondrial respiratory complex integrity and membrane potential are crucial for mast cell degranulation. Antigen stimulation raises reactive oxygen species (ROS) production from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria, leading to mast cell degranulation. Moreover, mast cell activation involved mitochondrial morphological changes and mitochondrial translocation to the cell surface near exocytosis sites. Interestingly, antioxidant administration reduced degranulation by lowering ROS levels. Altogether, these results highlight the crucial role of oxidative stress and mitochondria during anaphylaxis and mast cell degranulation. New therapeutics against anaphylaxis should probably target oxidative stress and mitochondria, in order to decrease anaphylaxis-induced systemic and major organ deleterious effects.