Acute Hypersensitivity Reactions Research Articles

Levetiracetam-Induced Acute Hypersensitivity Reaction in a Previously Undiagnosed Epilepsy Elderly Woman: A Case Report

Levetiracetam-Induced Acute Hypersensitivity Reaction in a Previously Undiagnosed Epilepsy Elderly Woman: A Case Report

Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. ObjectiveTo identify metabolites which are unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort (the Boston Birth Cohort). MethodsMass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (N=811). FA was diagnosed based on clinical symptoms consistent with an acute hypersensitivity reaction upon food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined based on physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders. ResultsDuring a median follow-up of 11.8±5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (OR=0.65, 95%CI=0.48-0.87) and 1-Oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR=0.77, 95%CI=0.66-0.90) were inversely associated with FA risk. Orotidine (OR=4.73, 95%CI=2.2-10.2) and 4-cholesten-3-one (OR=0.52, 95%CI=0.35-0.77) were the top two metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids. ConclusionIn this U.S. multi-ethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA, asthma, or both. These findings await further validation.

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.

(238) Hyaluronic Acid in Urology: Systematic Review and Meta-Analysis

Abstract Introduction Introduction: The use of hyaluronic acid (HA) as a non-surgical treatment for various pathological and cosmetic conditions within urology has been of great interest in recent literature. HA has been studied for use in several conditions including Peyronie’s disease, penile size augmentation, and premature ejaculation. Currently, HA is not first-line or standard therapy for any of these conditions; however, it has been increasingly utilized in clinical practice. Objective To provide an updated review and meta-analysis of the current state of hyaluronic acid use in urology, characterize its adverse effects, as well as briefly discuss future directions of research for HA in urology. Methods Multiple PubMed search strategies were run utilizing search terms, including: “hyaluronic acid”, “penile OR penis”, “augmentation”, “injection”, “enhancement”, “Peyronie disease”, “penile fibromatosis”, “premature ejaculation”, “cosmetic urology OR genital cosmetic”, “men’s health”, and “penile diseases” among other related iterations. Relevant data extracted included mean and standard deviation (for both pre- and post-HA injection or control treatment): International Index of Erectile Function (IIEF-5) score, intravaginal ejaculatory latency (IELT), glandular circumference/girth, erect penile girth, and plaque size Results Our search strategies yielded 136 studies of which 33 studies were included for systematic review (Figure 1). Among all studies, complications were generally rare with the procedure. 4 studies reported penile ecchymosis and a study reported paresthesia and numbness. There was 1 case report of glans penis necrosis, two of abscess formation, one of acute hypersensitivity reaction, and one of sepsis secondary to HA injection, which represented the most serious complications reported. Several studies also reported irregular nodule formation, which resolved with time or mild pressure application. In the metanalysis, 16 studies were included. IELT, penile girth, glans circumference, and IIEF-5 were all significantly increased on a fixed-effects model. 9 studies examined the change in IELT after HA injection, with an effect size of 2.335 [2.147,2.522], p-value= &amp;lt;0.001 (figure 2). Regardless of intent of study, 4 studies reported increase in glans circumference (figure 3) with effect size: 2.3 [2.066, 2.534], p-value= &amp;lt;0.001. Similarly, 4 studies showed increase in penile girth (figure 4) with effect size: 1.729 [1.504, 1.954], p-value = &amp;lt;0.001. 3 studies demonstrated IIEF-5 improvement with effect size: 0.996 [0.739–1.252], p-value= &amp;lt;0.001. With only 2 studies reporting pre- and post-op plaque length while others reporting the mean reduction in plaque amount, the plaque size was generally reduced after HA treatment, but this was not statistically significant, p-value= 0.069 with effect size: -0.252 [-0.524, 0.019]. It should be noted that of the 26 primary studies (excluding the 7 case reports), only 7 studies were randomized, controlled studies while others were either retrospective or single arm in nature. Conclusions While the use of HA in urology shows promising results in terms of efficacy and minimal side effects, there is a need for more randomized controlled trials to validate its potential advantages. Future research should focus on optimizing treatment protocols and exploring the expertise of sexual medicine specialists in administering HA therapy. Disclosure No.

Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling.

Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It is an exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or chronically are vascular occlusion leading to blindness and thoracic aorta aneurysm formation, respectively. The tissue inflammatory bulk is expressed as acute or chronic delayed-type hypersensitivity reactions, the latter being apparent by giant cell formation. The activated monocytes/macrophages are associated with pronounced Th1 and Th17 responses. B-cells and neutrophils also participate in the inflammatory lesion. However, the exact order of appearance and mechanistic interactions between cells are hindered by the lack of cellular and molecular information from early disease stages and accurate experimental models. Recently, senescent cells and neutrophil extracellular traps have been described in tissue lesions. These structures can remain in tissues for a prolonged period, potentially favoring inflammatory responses and tissue remodeling. In this review, current advances in GCA pathogenesis are discussed in different inflammatory phases. Through the description of these-often overlapping-phases, cells, molecules, and small lipid mediators with pathogenetic potential are described.

(253) Usage of Hyaluronic Acid in Urology: Systematic Review and Meta-Analysis

Abstract Introduction The use of hyaluronic acid (HA) as a non-surgical treatment for various pathological and cosmetic conditions within urology has been of great interest in recent literature. HA has been studied for use in several conditions including Peyronie’s disease, penile size augmentation, and premature ejaculation. Currently, HA is not first-line or standard therapy for any of these conditions; however, it has been increasingly utilized in clinical practice. Objective To provide an updated review and meta-analysis of the current state of hyaluronic acid use in urology, characterize its adverse effects, as well as briefly discuss future directions of research for HA in urology. Methods Multiple PubMed search strategies were run utilizing search terms, including: “hyaluronic acid”, “penile OR penis”, “augmentation”, “injection”, “enhancement”, “Peyronie disease”, “penile fibromatosis”, “premature ejaculation”, “cosmetic urology OR genital cosmetic”, “men’s health”, and “penile diseases” among other related iterations. Relevant data extracted included mean and standard deviation (for both pre- and post-HA injection or control treatment): International Index of Erectile Function (IIEF-5) score, intravaginal ejaculatory latency (IELT), glandular circumference/girth, erect penile girth, and plaque size. Results Our search strategies yielded 136 studies of which 33 studies were included for systematic review (Figure 1). Among all studies, complications were generally rare with the procedure. 4 studies reported penile ecchymosis and a study reported paresthesia and numbness. There was 1 case report of glans penis necrosis, two of abscess formation, one of acute hypersensitivity reaction, and one of sepsis secondary to HA injection, which represented the most serious complications reported. Several studies also reported irregular nodule formation, which resolved with time or mild pressure application. In the metanalysis, 16 studies were included. IELT, penile girth, glans circumference, and IIEF-5 were all significantly increased on a fixed-effects model. 9 studies examined the change in IELT after HA injection, with an effect size of 2.335 [2.147,2.522], p-value= &amp;lt;0.001 (figure 2). Regardless of intent of study, 4 studies reported increase in glans circumference (figure 3) with effect size: 2.3 [2.066, 2.534], p-value= &amp;lt;0.001. Similarly, 4 studies showed increase in penile girth (figure 4) with effect size: 1.729 [1.504, 1.954], p-value = &amp;lt;0.001. 3 studies demonstrated IIEF-5 improvement with effect size: 0.996 [0.739-1.252], p-value= &amp;lt;0.001. With only 2 studies reporting pre- and post-op plaque length while others reporting the mean reduction in plaque amount, the plaque size was generally reduced after HA treatment, but this was not statistically significant, p-value= 0.069 with effect size: -0.252 [-0.524, 0.019]. It should be noted that of the 26 primary studies (excluding the 7 case reports), only 7 studies were randomized, controlled studies while others were either retrospective or single arm in nature. Conclusions While the use of HA in urology shows promising results in terms of efficacy and minimal side effects, there is a need for more randomized controlled trials to validate its potential advantages. Future research should focus on optimizing treatment protocols and exploring the expertise of sexual medicine specialists in administering HA therapy. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

Absolute zero-contrast percutaneous coronary interventions: An intravascular ultrasound-guided case series and literature review

PurposeContrast media (CM)-associated adverse effects including mainly acute kidney injury and hypersensitivity reactions still remain a significant treatment burden to vulnerable patients requiring percutaneous coronary intervention (PCI). The complete omission of CM administration accompanied by intravascular ultrasound (IVUS) guidance may offer an appropriate revascularization treatment. MethodsWe hereby present a case series of four patients with challenging coronary lesions and relative/absolute contraindications to CM use [(hypersensitivity reaction owning to CM, history of contrast-induced acute kidney injury, solitary kidney, or advanced chronic kidney disease (CKD)] who underwent absolute zero-contrast IVUS-guided PCI following a predetermined protocol. ResultsThe initial diagnostic angiography was reviewed for landmark identification, and multiple guidewires created a metallic road map providing additional landmarks and protected side branches. IVUS imaging was performed to determine lesion length, reference segments and landing zones, assess stent expansion/apposition and identify major complications. All procedures were successfully completed without any CM administration, renal function deterioration, pericardial effusion, or stent edge dissection. ConclusionsWe demonstrated the feasibility of absolute zero-contrast IVUS-guided PCI in patients with complex coronary lesions susceptible to CM-associated adverse effects. Since the safety of this strategy is well-documented in patients with CKD and challenging lesions morphology even in acute settings, evidence-based validation of this approach is capable of changing the otherwise conservative treatment of vulnerable patients where even minimum doses of CM may have detrimental effects. Summary for the annotated table of contentsPatients with vulnerable renal function as well as former hypersensitivity reaction to contrast media encounter a significant treatment burden regarding coronary artery disease. Zero-contrast IVUS-guided strategy based on a predetermined protocol provides a feasible alternative approach in patients susceptible to contrast media-associated adverse effects even in the presence of complex coronary lesions.

The efficacy and toxicity of L-asparaginase in the treatment of acute lymphoblastic leukemia in children

L-asparaginase, an enzyme used as an anticancer drug, was one of the first drugs included in the treatment protocols for acute lymphoblastic leukemia. It has become widely used when an important metabolic feature of leukemia cells – their high demand for asparagine to maintain viability – was discovered. Three L-asparaginase preparations are currently used in clinical practice: native E. coli asparaginase, pegylated E. coli asparaginase (PEG-asparaginase), and native E. chrysanthemi-derived asparaginase, which have different half-lives, immunogenic profiles, and the spectrum and frequency of toxic effects. One of the main factors limiting the use of L-asparaginase is its high immunogenicity which can cause acute allergic reactions and the phenomenon of silent inactivation. The development of the immune response leads to an accelerated asparaginase clearance and a shortening of its half-life. To monitor the effectiveness of therapy with L-asparaginase, therapeutic drug monitoring of serum asparaginase activity can be used. When choosing management strategies for patients experiencing acute hypersensitivity reactions to L-asparaginase, the following factors should be taken into consideration: the severity of reaction, the number of previous exposures to L-asparaginase and serum asparaginase activity. The use of PEG-asparaginase is the best first-line treatment strategy for children acute lymphoblastic leukemia, its advantages include a significant reduction in the risk of developing acute allergic reactions, higher therapeutic efficacy and, as a result, improved treatment outcomes.

Preventing post-contrast acute kidney injury and hypersensitivity reactions: UK national audit

To audit UK radiology departmental protocols related to the prevention of Iodine-based contrast media (ICM) adverse drug reactions (ADRs) and to assess their compliance with the Royal College of Radiologists (RCR) endorsed Royal Australian and New Zealand College of Radiologists' 2018 Iodinated Contrast Guidelines. Questionnaires were sent to all UK acute National Health Service (NHS) providers treating adult patients with an audit lead registered with the RCR (162 providers encompassing 211 hospital radiology departments). The questionnaire included three main sections: renal function screening, renal protection regimens, and hypersensitivity reactions prevention and follow-up. Data collection was conducted between April and July 2022. Sixty-one per cent (129/211) of departments responded, representing 67% of eligible providers. An independent imaging services provider supplied one additional set of data (n=130 overall). Of the responding departments, for post-contrast acute kidney injury (PC-AKI), 41% and 56% had the recommended risk assessment for inpatients and outpatients, respectively. Renal function testing was often over-utilised, and their results were applied improperly. Sixty-eight per cent of departments used the advised threshold for considering renal protection. For hypersensitivity reactions, 9% of departments had the correct risk assessment. Thirty-six per cent of departments had the correct risk mitigation protocol for identified high-risk patients. The documentation and follow-up for hypersensitivity reactions were similarly inadequate. Local protocols on preventing ICM ADRs were largely non-compliant with RCR guidelines. Departments need to update their protocols in line with current evidence to avoid iatrogenic morbidity or unnecessary tests and over-precaution.

Biologics to treat anaphylaxis.

The purpose of this literature review was to review the latest use of biologics in the management of anaphylaxis. The methodology was to highlight both the nonbiologic management of anaphylaxis and the biologic management and how they can be used in conjunction with each other. As the phenotypes and endotypes of anaphylaxis are better portrayed, it furthers our understanding of the mechanisms of anaphylaxis. New applications of existing biologics to the prevention of anaphylaxis are described. Anaphylaxis is a potentially life-threatening acute hypersensitivity reaction affecting up to 16.8% of the U.S. population. Acute management entails swift identification, removal of the causative agent, and the prevention of cardiovascular collapse, firstly with epinephrine. Adjunctive treatments such as antihistamines work to prevent anaphylaxis from recurring. Biologic management of anaphylaxis involves the use of large-molecule drugs such as monoclonal antibodies. Omalizumab, an IgG1 monoclonal antibody targeting unbound IgE, is the most prevalent and widely studied biologic in the prevention of anaphylaxis. Other monoclonal antibodies in development or approved for other indications, such as ligelizumab, quilizumab, MEDI4212, and dupilumab, may also have potential for preventing anaphylaxis through various mechanisms.

Kounis syndrome in a patient following AstraZeneca coronavirus disease 2019 vaccination: a case report

Introduction and importanceKounis syndrome, also known as allergic angina syndrome, is defined as the occurrence of an acute coronary syndrome concomitantly with a hypersensitivity reaction. It is a very important diagnosis and missing it may be fatal to the patient. This is a medical emergency, and immediate treatment should be initiated. The treatment of Kounis syndrome is challenging because treatment of either acute coronary syndrome and hypersensitivity reaction can lead to the worsening of the other injury. This case is the first reported case of Kounis syndrome following coronavirus disease 2019 vaccination in Sri Lanka according to our knowledge.Case presentationWe discuss a 54-year-old female Sri Lankan patient who developed Kounis syndrome following Oxford AstraZeneca COVID-19 vaccination. The patient initially developed anaphylaxis following the AstraZeneca COVID-19 vaccine and subsequently developed acute coronary syndrome secondary to anaphylaxis. The patient was treated appropriately and eventually recovered from her condition.ConclusionThis syndrome should be suspected when there is a concurrent acute coronary syndrome with allergic reactions. This is an often under- or misdiagnosed condition, and physicians should be educated about it. Caregivers should be aware of its pathophysiology, as treatment of either of the two may worsen the other injury.

TREATMENT OF HERPES ASSOCIATED ERYTHEMA MULTIFORME (HAEM)

Introduction: Herpes Associated Erythema Multiforme (HAEM) is Erythema multiforme (EM) caused herpes virus infection. EM a caused by an acute hypersensitivity reaction that occurs in the mucocutaneous area. HAEM is hypersensitivity reaction that occurs due to a hypersensitivity reaction to the herpes virus. Case: 17 year old male complaints of itching and dry on his lips since 5 days ago. patient said that ± 7 days ago he had a fever which lasted for 2 days then after the fever went down his lips felt itchy and dry. On clinical examination, desquamation with yellowish brown crusts was found on the vermilion of the upper and lower lips. Case Treatment: patient is given Aloclair® Gel and Becomzet®. Patient is referred for a complete blood count, Total IgE and IgM and IgG HSV-1 antibody testing. The patient was then given hydrocortisone cream 2.5% used 3 times a day. The patient recovered 10 days after the first visit. Discussion: HAEM is triggered by an immunological response in which an immune complex reaction occurs as a result of an immune response to certain antigens such as the herpes simplex virus or certain types of drugs. In cases of HAEM the herpes virus that triggers it is usually HSV-1 &amp; HSV-2. Diagnosis is confirmed by Total IgE and HSV-1 Antibody Tests. Conclucion: Management of cases of HAEM can be successfully determined by establishing the correct diagnosis which requires investigations so that we can rule out the differential diagnosis and provide appropriate treatment

Evaluation and Updated Classification of Acute Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAID-Exacerbated or -Induced Food Allergy (NEFA/NIFA).

There are hypersensitivity reactions (HRs) to foods in which nonsteroidal anti-inflammatory drugs (NSAIDs) act as aggravating factors (NSAID-exacerbated food allergy, NEFA) or cofactors (NSAID-induced food allergy, NIFA), often misdiagnosed as HRs to NSAIDs. Urticarial/angioedematous and/or anaphylactic reactions to ≥ 2 chemically unrelated NSAIDs do not meet the current classification criteria. However, they may be considered as part of a cross-reactive type of acute HR, which is NSAID-induced urticaria/angioedema with/without respiratory and/or systemic symptoms of anaphylaxis (NIUAA). To evaluate patients reporting acute HRs to NSAIDs and classify them according to updated criteria. 414 patients with suspected HRs to NSAIDs were studied prospectively. NEFA/NIFA was diagnosed in those who met all the following criteria: 1) mild reactions to (NEFA) or tolerance of (NIFA) the suspected foods without taking NSAIDs; 2) cutaneous and/or anaphylactic reactions to the combination foods + NSAIDs; 3) positive allergy tests to the suspected foods; 4) negative drug challenges (DCs) with the NSAIDs involved. 252 patients (60.9%) were diagnosed with NSAID hypersensitivity, 108 of whom had NIUAA. NSAID hypersensitivity was excluded in 162 patients (39.1%) who tolerated DCs with the suspected NSAIDs, 9 of whom were diagnosed with NEFA and 66 with NIFA. Pru p 3 was implicated in 67 of these 75 cases. NEFA/NIFA accounts for about 18% of patients reporting HRs to NSAIDs, with Pru p 3 as the main responsible food allergen. Therefore, patients with cutaneous and/or anaphylactic reactions to NSAIDs should be carefully questioned about all foods ingested within 4 hours before or after NSAID exposure, and targeted food allergy tests should be considered in the diagnostic workup of these patients. If testing is positive, DCs with the suspected NSAIDs should also be considered.

Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.

Platelet-activating factor as an endogenous cofactor of food anaphylaxis.

Anaphylaxis is a severe, acute, life-threatening generalized or systemic hypersensitivity reaction. The incidence of anaphylaxis is increasing worldwide, with medications and food contributing to most cases. Physical exercise, acute infections, drugs, alcohol, and menstruation are the external cofactors associated with more severe systemic reaction. The aim of this review is to show that platelet-activating factor contributes to the development of severe anaphylactic reaction, and even to anaphylactic shock.

Management of Suspected Life-Threatening Perioperative Anaphylaxis and Risk Factors for Near-Fatal and Fatal Outcomes: A Retrospective Study in China.

Perioperative anaphylaxis (POA) is an acute severe systemic hypersensitivity reaction characterized by life-threatening respiratory and circulatory collapse. In our previous study, we reported the epidemiology of suspected POA in China. In the present study, we aimed to elucidate the management and outcomes of these cases and further verify the risk factors for near-fatal and fatal outcomes. This was a retrospective study of 447 cases of suspected life-threatening POA encountered at 112 tertiary hospitals in mainland China between September 2018 and August 2019. Patient characteristics, symptoms, duration of hypotension, treatments, and clinical outcomes were documented. Bivariate logistic regression was used to identify risk factors for near-fatal and fatal outcomes. Most cases of suspected POA (89.9%) were recognized and treated within 5 min. Epinephrine was administered as the initial treatment in 232 (51.9%) cases. Corticosteroids (26.6%), other vasoactive drugs (18.3%), and bronchodilators (1.6%) were also administered as the initial treatment instead of epinephrine. The initial dosage of epinephrine (median, 35 µg) was insufficient according to the anaphylaxis guidelines. On multivariable analysis, age ≥65 years (odds ratio [OR] 7.48; 95% confidence interval [CI]: 1.33-41.87, P=0.022), ASA physical status IV (OR 17.68; 95% CI: 4.53-68.94; P<0.001), and hypotension duration ≥15 min (OR 3.63; 95% CI: 1.11-11.87; P=0.033) were risk factors for fatal and near-fatal outcomes. Most cases in this study were managed in a timely manner, but the epinephrine application should be optimized according to the guidelines. Age ≥65 years, ASA physical status IV, and long-term hypotension were risk factors for near-fatal and fatal outcomes.

Acute and chronic inflammation alter immunometabolism in a cutaneous delayed-type hypersensitivity reaction (DTHR) mouse model

T-cell-driven immune responses are responsible for several autoimmune disorders, such as psoriasis vulgaris and rheumatoid arthritis. Identification of metabolic signatures in inflamed tissues is needed to facilitate novel and individualised therapeutic developments. Here we show the temporal metabolic dynamics of T-cell-driven inflammation characterised by nuclear magnetic resonance spectroscopy-based metabolomics, histopathology and immunohistochemistry in acute and chronic cutaneous delayed-type hypersensitivity reaction (DTHR). During acute DTHR, an increase in glutathione and glutathione disulfide is consistent with the ear swelling response and degree of neutrophilic infiltration, while taurine and ascorbate dominate the chronic phase, suggesting a switch in redox metabolism. Lowered amino acids, an increase in cell membrane repair-related metabolites and infiltration of T cells and macrophages further characterise chronic DTHR. Acute and chronic cutaneous DTHR can be distinguished by characteristic metabolic patterns associated with individual inflammatory pathways providing knowledge that will aid target discovery of specialised therapeutics.

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database

ABSTRACT Background We study the adverse events (AEs) of bamlanivimab (BAM), bamlanivimab/etesevimab (BAM/ETE) to alert risk factors during coronavirus disease 2019 (COVID-19) treatment and provide references for drug safety. Research design and methods Extract AEs from the COVID-19 Emergency Use Authorization (EUA) FDA Adverse Event Reporting System (FAERS) Public Dashboard. Disproportionality analysis was performed to discover the potential risks of BAM and BAM/ETE. Results With COVID-19 drugs as the research background, the number of BAM/ETE signals is about half that of BAM, and 80% of signals overlap with BAM. Signals such as atrial fibrillation, tachycardia, and confusional state are present in BAM but not in BAM/ETE. With BAM and BAM/ETE as the research background, potential safety signals of BAM/ETE such as acute respiratory failure, hypersensitivity, and infusion-related reaction require long-term observation, especially acute respiratory failure which is not in the label. Conclusions The AEs report on this study confirm most of the label information of BAM and BAM/ETE. BAM/ETE is relatively safe, while the risk signals such as acute respiratory failure and infusion-related reaction require to be monitored.

Hypersensitivity to Intravenous Iron Preparations.

Intravenous iron is widely used for the treatment of iron deficiency anemia when adherence to oral iron replacement is poor. Acute hypersensitivity reactions during iron infusions are very rare but can be life threatening. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, atopic diseases, high serum tryptase levels, asthma, and urticaria. The management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. Avoidance of IV iron products in patients with iron hypersensitivity reactions may not be considered as a standard practice.

1200TiP Phase Ia/Ib study of RS-0139, a novel tumor-targeted delivery of docetaxel, in patients with recurrent, locally advanced, or metastatic non-small cell lung cancer (NSCLC)

Docetaxel (DTX) is an anti-microtubule agent registered for multiple indications and is usually administered 3-weekly at doses of 60-100 mg/m2. Important limitations of DTX include acute hypersensitivity reactions, neutropenia, neuropathy, fatigue and nausea. RS-0139 is developed as a DTX-releasing, tumor-targeted prodrug. DTX is covalently bound to a polymer backbone, together with a targeting peptide, which shows high affinity to avb3, avb5 and avb6 integrin receptors highly expressed on tumor cell surface. Once RS-0139 is up-taken by the cell, the covalent bond is cleaved to release DTX in the cytoplasm. RS-0139 gains the investigational new drug status since DTX is covalently modified for the targeted treatment. The physical properties of RS-0139, pharmacokinetic profile and improved aqueous solubility may provide an advantage over the currently used taxanes. In preclinical studies, enzymatically cleavable covalent conjugation of DTX enabled sustained-release inside the tumor, reducing adverse effects due to limited circulating free DTX. Hence, RS-0139 showed superior tolerability than DTX in healthy animals. Besides, the dosing frequency decreased owing to the increased half-life. Preclinical data strongly support the clinical translation of this novel nanomedicine for the treatment of solid tumors. This is a phase Ia/Ib open-label, multicenter, dose-escalation and expansion study to evaluate the safety and tolerability of RS-0139 monotherapy in NSCLC. Patients who progressed after standard therapy are eligible for the study. In Phase Ia, patients receive RS-0139 (IV) at escalating doses (75-200 mg/m2). The protocol consists of an accelerated titration design until the recommended dose for Phase Ib is elicited and switched to standard 3+3 design in case of grade 2 toxicity. Phase Ib will be initiated following the determination of the recommended dose for RS-0139 upon evaluation of all available safety and PK data and 6 patients will receive 3 cycles in every 21 days. The primary endpoint is the determination of the MTD of RS-0139. The study is open for enrollment in 2 sites. Two of the planned 16 patients have been enrolled to date. NCT04261413. RS Research.