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Background: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI., Objective: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI., Methods: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022., Results: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission., Conclusion: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity., (© 2024. The Author(s).)

Background: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology., Objective: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD., Methods: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles., Results: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts., Conclusion: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy)., Competing Interests: Disclosures Detailed in the Methods and eAppendix, the Guidelines followed JTFPP policies and international standards for addressing potential conflicts of interest. All JTFPP members’ COI are available publicly at https://www.allergyparameters.org., (Copyright © 2023. Published by Elsevier Inc.)

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., Competing Interests: Disclosures The JTFPP members and workgroup members’ conflict of interest disclosure forms can be found at www.allergyparameters.org. Dr Golden: clinical trial support from Genentech, ThermoFisher, Novartis, Pfizer, GlaxoSmithKline, and Regeneron; consulting fees from Aquestive, Novartis, ThermoFisher, ALK-Abello, Allergy Therapeutics; and royalties from UpToDate. Dr Wang: clinical trials support (money to institution) from NIH, Aimmune, DBV Technologies, Regeneron, and Siolta; consulting fees from ALK-Abello, Jubilant HollisterStier; and royalties from UpToDate. Dr Waserman: consulting fees from GlaxoSmithKline, Novartis, CSL Behring, Pfizer Canada, Sanofi Canada, AstraZeneca, Takeda, ALK-Abello, Teva, Medexus, MiravoHealth, Mylan, Bausch Lomb, AbbVie, Avir Pharma, and Leo Pharma; research funding from Pfizer Canada, ALK-Abello, Aimmune; and president of Canadian Allergy, Asthma and Immunology Foundation. Dr Akin: consulting fees from Blueprint Medicine, Cogent, and Novartis; research support from Blueprint Medicines and Cogent; and royalties from UpToDate. Dr Campbell: consulting fees from Bryn and royalties from UpToDate. Dr Ellis: advisory boards for ALK-Abello, AstraZeneca, Aralez, Bausch Health, Leo Pharma, Merck, Novartis, and Pfizer; speakers’ bureaus for ALK-Abello, AstraZeneca, Miravo, Medexus, and Mylan; research support (paid to institution) from ALK-Abello, Aralez, AstraZeneca, Bayer LLC, Medexus, Novartis, and Regeneron; independent consultant to Bayer LLC and Regeneron; and royalties from UpToDate. Dr Greenhawt: consultant for Aquestive; advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, and Prota; scientific advisory council (unpaid) for the National Peanut Board and medical advisory board (unpaid) of the International Food Protein Induced Enterocolitis Syndrome Association; Working Group Member of the Brighton Collaboration Criteria Vaccine Anaphylaxis; senior associate editor for Annals of Allergy, Asthma & Immunology; member of the Joint Task Force on Allergy Practice Parameters; and speaker honoraria from ImSci, MedLearningGroup, RMEI Medical Education and multiple state/local allergy societies. Dr Lang: honoraria, consultant, and/or clinical research support from AstraZeneca, Genentech, Novartis, and Sanofi-Regeneron; Guest Associate Editor of JACI:In Practice; and editorial board of DynaMed. Dr Ledford: contributor to UpToDate for Perioperative Anaphylaxis; contributing editor for Ask the Expert (AAAAI); research support from AstraZeneca and Novartis (paid to institution); consultant for AstraZeneca; speaker bureau/honoraria from AstraZeneca, Genentech, GlaxoSmithKline, and Sanofi/Regeneron; and legal opinion indoor fungal exposure, drug allergy, anaphylaxis. Dr Lieberman: contracted research (paid to institution) for Aimmune, DBV, Regeneron, and Novartis; adjudication/DSMB for AbbVie and Siolta; consultant/advisor for Aquestive, ALK-Abello, Novartis, and DBV. Dr Oppenheimer: Executive Editor of Annals of Allergy, Asthma & Immunology; reviewer for UpToDate; adjudication and data safety monitoring board for AstraZeneca, GlaxoSmithKline, and Sanofi; consultant for GlaxoSmithKline, Aquestive, and Aimmune; NIH grant for the IDEA study. Dr Shaker: editorial board of The Journal of Allergy and Clinical Immunology: In Practice; associate editor of Annals of Allergy, Asthma & Immunology; member of the Joint Task Force on Practice Parameters; and research support from DBV. Dr Wallace: consulting fees from AbbVie, Bryn, Sanofi, and Kaleo. Dr Abrams: employee of Public Health Agency of Canada (PHAC); views expressed are my own and not those of PHAC. Dr Bernstein: principal investigator, consultant, and speaker for Novartis, Genentech, AstraZeneca, Sanofi Regeneron, Takeda/Shire, CSL Behring, Pharming, BioCryst, and Merck; consultant for Kalvista, Ionis, Celldex, Allakos, Amgen, Biomarin, and Blueprint Medicine; principal investigator and speaker for GlaxoSmithKline; speaker for Optinose; consultant for Ono, Astria, Incyte, Cycle, and Escient; and royalties from UpToDate, British Medical Journal, Taylor & Francis, and Elsevier. Dr Stukus: consultant for ARS Pharmaceuticals, Before Brands, Novartis, and ParentMD; research support from DBV Technologies; social media editor for the AAAAI; member, board of regents for the ACAAI; and Associate Editor, Annals of Allergy, Asthma & Immunology. Heather Cruickshank: grant support from AllerGen NCE and medical writer for Healthline Media. The remaining authors have no conflicts of interests to report., (Copyright © 2023. Published by Elsevier Inc.)

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear., Objective: We systematically synthesized the evidence addressing INCS for CRSwNP., Methods: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach., Results: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others)., Conclusions: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied., Objective: We sought to determine the clinical consequences of nocturnal asthma symptoms requiring albuterol (NASRAs) in children with mild-to-moderate persistent asthma outside of periods when oral corticosteroids were used for worsening asthma symptoms., Methods: Two hundred eighty-five children aged 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of 3 controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of NASRAs., Results: NASRAs occurred in 72.2% of participants at least once, and in 24.3% of participants, they occurred 13 or more times. The majority (81.3%) of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use (56.9% of days preceded by nocturnal symptoms vs 18.1% of days not preceded by nocturnal symptoms; relative risk [RR], 2.3; 95% CI, 2.2-2.4), school absence (5.0% vs 0.3%; RR, 10.6; 95% CI, 7.8-14.4), and doctor contact (3.7% vs 0.2%; RR, 8.8; 95% CI, 6.1-12.5). Similar findings were noted during exacerbation periods (RRs of 1.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contacts). Nocturnal symptoms did not predict the onset of exacerbations., Conclusion: Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Finite element analysis (FEA) is used by industrial designers and biomechanicists to estimate the performance of engineered structures or human skeletal and soft tissues subjected to varying regimes of stress and strain. FEA is rarely applied to problems of biomechanical design in animals, despite its potential to inform structure-function analysis. Non-invasive techniques such as computed tomography scans can be used to generate accurate three-dimensional images of structures, such as skulls, which can form the basis of an accurate finite element model. Here we have applied this technique to the long skull of the large carnivorous theropod dinosaur Allosaurus fragilis. We have generated the most geometrically complete and complex FEA model of the skull of any extinct or extant organism and used this to test its mechanical properties and examine, in a quantitative way, long-held hypotheses concerning overall shape and function. The combination of a weak muscle-driven bite force, a very 'light' and 'open' skull architecture and unusually high cranial strength, suggests a very specific feeding behaviour for this animal. These results demonstrate simply the inherent potential of FEA for testing mechanical behaviour in fossils in ways that, until now, have been impossible.

Protein kinase C (PKC) translocation to specific subcellular membrane loci after cellular stimulation is mediated, in part, through its interaction with diacylglycerol, phosphatidylserine, and calcium. Herein, we present multiple lines of evidence which demonstrate that purified rabbit brain PKC undergoes specific acylation with palmitoyl CoA that facilitates its interaction with membrane bilayers. First, incubation of purified rabbit brain PKC with [14C]palmitoyl CoA (5 microM) resulted in the radiolabeling of an 80 kDa band demonstrated by SDS-PAGE and autoradiography, while incubation of PKC with other acyl CoA molecular species (e.g., [3H]myristoyl CoA or [14C]arachidonoyl CoA), fatty acids (e.g., [14C]palmitic and [14C]arachidonic acid), or [14C]diacylglycerol did not result in the incorporation of radiolabel. Second, multiple extractions of [14C]palmitoyl CoA-treated PKC with butanol did not remove the radiolabeled moiety from the 80 kDa PKC band. Third, incubation of the [14C]palmitoyl CoA-radiolabeled PKC moiety with neutral hydroxylamine, hydrochloric acid, or sodium hydroxide released incorporated radiolabel which identified the association between PKC and palmitic acid as a covalent thioester linkage. Fourth, formation of the [14C]palmitoyl CoA-radiolabeled PKC adduct could be prevented by pretreatment of PKC with either dithiobis(nitrobenzoic acid) or N-ethylmaleimide. Fifth, limited trypsinolysis of palmitoylated PKC demonstrated that palmitic acid was exclusively present in the regulatory fragment of PKC without detectable amounts of palmitic acid associated with the catalytic fragment. Sixth, palmitoylated PKC was resolved from its nonpalmitoylated counterpart by Mono Q chromatography, and palmitoylated PKC preferentially associated with cellular membranes while nonpalmitoylated PKC did not. Both palmitoylated and nonpalmitoylated PKC were activated by phosphatidylserine, diacylglycerol, and calcium ion. Collectively, these results demonstrate the acylation of PKC by palmitoyl CoA and identify a novel mechanism which may facilitate the interaction of PKC with biologic membranes.

Long-chain acylcarnitines accumulate during myocardial ischemia and contribute to membrane dysfunction in ischemic zones. On the basis of the 3-fold selectivity for saturated fatty acid accumulation during myocardial ischemia, it was implicitly assumed that saturated long chain acylcarnitine molecular species predominantly accumulated in ischemic myocardium. By exploiting the analytical power of electrospray ionization mass spectroscopy, we now report that unsaturated acylcarnitines are the predominant molecular species of acylcarnitine which accumulate during myocardial ischemia (rank order: octadecadienoyl carnitine > octadecanoyl carnitine > hexadecanoyl carnitine > octadecanoyl carnitine). The aliphatic chain distribution of myocardial acylcarnitine molecular species identified by electrospray ionization mass spectroscopy was independently substantiated by sequential HPLC purification and capillary gas chromatography. Detailed analysis of the individual molecular species of long-chain acylcarnitine demonstrated that fatty acyl chain elongation was prominent in ischemic myocardium (e.g., following 20 min of ischemia, greater than 15% of the accumulated acylcarnitines consisted of 20-carbon unsaturated molecular species). Chain-elongated lipids were essentially confined to the long chain acylcarnitine pool since [9,10-3H]octadec-9'-enoic acid was converted to [3H]eicosenoyl carnitine (12% of the radiolabeled acylcarnitine pool) in ischemic hearts without substantive amounts of [3H]eicosenoyl residues in the fatty acid, triglyceride, and phospholipid pools. Collectively, these results demonstrate the preponderance of unsaturated acylcarnitines in ischemic myocardium and document the metabolic compartmentation of downstream products of fatty acyl chain elongation in the acylcarnitine pool during ischemia.