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Alessandro Fiocchi,1 R Sharon Chinthrajah,2 Ignacio J Ansotegui,3 Panida Sriaroon,4 S Shahzad Mustafa,5 Pranil Raut,6 Briana Cameron,6 Sachin Gupta,1 David M Fleischer7 1Bambino Gesù Childrens’ Hospital IRCCS, Rome, Italy; 2Stanford University, Stanford, CA, USA; 3Hospital Quironsalud Bizkaia, Bilbao, Spain; 4University of South Florida, Tampa, FL, USA; 5Rochester Regional Health & University of Rochester, Rochester, NY, USA; 6Genentech Inc., South San Francisco, CA, USA; 7Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USACorrespondence: David M Fleischer, Section Head, Allergy & Immunology, University of Colorado School of Medicine and Children’s Hospital Colorado, 13123 East 16th Avenue, B518, Aurora, CO, 80045, USA, Tel +1-720-777-4393, Email David.Fleischer@childrenscolorado.orgBackground: The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy.Patients and Methods: We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data.Results: For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy.Conclusion: There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities.Clinical trial registration: NCT00079937; NCT01922037; NCT00252135.Plain Language Summary: Food allergy and asthma are linked and if you have both conditions then you can feel worse. There is a treatment available, called omalizumab, that helps people with asthma and helps people with food allergy, but it’s not clear if it can help people with both conditions. Here, we look at whether omalizumab can help people with bad to very bad asthma (also called moderate to severe asthma) who also have food allergy. We found that omalizumab improved many aspects of a person’s life, including whether they visited the emergency room, were admitted to hospital, their quality of life, whether they missed school or work, and whether their asthma improved. These improvements occurred in all people with moderate to severe asthma, whether they had food allergy or did not have food allergy. This suggests that omalizumab can help people with both conditions.Keywords: asthma, food allergy, food hypersensitivity, healthcare resource use, omalizumab, productivity, quality of life

Syeda Samar Mustafa,1 Rida Batool,1 Muhammad Kamran,2 Hasnain Javed,3 Nazia Jamil1 1Institute of Microbiology and Molecular Genetics, Quaid e Azam Campus, University of the Punjab 54590, Lahore, Pakistan; 2Queensland Alliance for Agriculture and Food Innovation Centre for Animal Science, University of Queensland, Brisbane, Queensland, 4072, Australia; 3Provincial Public Health Reference Lab, Punjab AIDS Control Program, Lahore, PakistanCorrespondence: Syeda Samar Mustafa, Email samarmustafa14@gmail.comIntroduction: Wastewaters carrying thousands of human specimens from the community and representing the diversity of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) directly from the community mirror the extent of AR spread in the community and environment. This study aimed to investigate the occurrence and distribution of antibiotic-resistant ESKAPEE bacteria in the community versus clinical settings through monitoring nonclinical and clinical wastewaters.Methodology: Seven wastewater samples were collected from different environmental sources. Isolates were obtained on general and selective media, biochemically characterized and antimicrobial-susceptibility tests performed by disk diffusion against 13 antibiotics according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines using MastDisc disk cartridges, and 16S rRNA metagenomic analysis was performed for two water samples.Results: Of 43 isolates, all representatives of the ESKAPEE group were recovered from clinical wastewaters, but Gram-positive cocci were not obtained from nonclinical wastewaters. The most predominant isolate was Pseudomonas aeruginosa (n=15; 33%), followed by Escherichia coli (n=9; 20%). Complete (100%) resistance to eleven of the tested antibiotics was observed, with only a few isolates being susceptible to clarithromycin, amikacin, and gentamicin. The lowest (79%) resistance rate was observed for linezolid. The multiple antibiotic resistance (MAR) index was calculated, and the resistance phenotype was independent of the wastewater source, indicated by x2 (P=0.766). Metagenomic analysis replicated the results, as Pseudomonas spp., Acinetobacter spp., and Escherichia spp. were found to be predominant. The integrase gene (IntI1) was also amplified in Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.Conclusion: Wastewaters are significant carriers of drug-resistant ESKAPEE bacteria and play an important role in their dissemination. This study endorses the periodic surveillance of water systems to evaluate the presence and burden of antibiotic-resistant pathogens.Graphical Abstract: Keywords: resistance profiling, ESKAPEE, wastewater, metagenome, IntI1

Background: Anaemia is a global health problem affecting 1.62 billion people where 41.8% (56 million people) of the general population are pregnant women. It’s more prevalent among pregnant women because during pregnancy, iron requirements increase much more significantly as compared to non-pregnant women. The aim of conducting this study was to determine the factors influencing the prevalence of anaemia among pregnant women attending antenatal care (ANC) services at Kabale Regional Referral Hospital (KRRH) in Kabale district. Methods: A hospital based cross-sectional study was conducted among pregnant mothers. Data was collected using a systematic random sampling technique. Blood samples were collected from 200 pregnant women and analyzed using a CBC analyzer sysmex Xs1000 to determine the Haemoglobin concentration. Interviews were conducted with mothers to determine factors influencing the prevalence of anaemia. Results: Findings showed that the general prevalence of anaemia was 27% whereby 31% were mildly anaemic, 50% were moderately anaemic and 19% were severely anaemic. Concerning the socio-economic factors influencing the prevalence of anaemia among pregnant women, it was found out that the prevalence of anaemia was higher among participants who were peasants, rural dwellers, those having low education and low monthly income. The level of awareness about anaemia among pregnant women was 68% whereby the majority (25.5%) had heard it from ANC clinic. Conclusion: The overall prevalence of anaemia (27%) among pregnant women attending antenatal care services at Kabale Regional Referral Hospital in Kabale district was found to be a moderate health problem in the area of study.

Background: Limited decision-support tools are available to help shared decision-making (SDM) regarding food oral immunotherapy (OIT) initiation. No current tool covers all foods, forms, and pediatric ages for which OIT is offered., Methods: In compliance with International Patient Decision Aid Standards criteria, this pediatric decision-aid comparing OIT versus avoidance was developed in three stages. Nested qualitative data assessing OIT decisional needs were supplemented with evidence-synthesis from the OIT literature to create the prototype decision-aid content. This underwent iterative development with food allergy experts and patient advocacy stakeholders until unanimous consensus was reached regarding content, bias, readability, and utility in making a choice. Lastly, the tool underwent validated assessment of decisional acceptability, decisional conflict, and decisional self-efficacy., Results: The decision-aid underwent 5 iterations, resulting in a 4-page written aid (Flesch-Kincaid reading level 6.1) explaining therapy choices, risks and benefits, providing self-rating for attribute importance for the options and self-assessment regarding how adequate the information was in decision-making. A total of n = 135 caregivers of food-allergic children assessed the decision-aid, noting good acceptability, high decisional self-efficacy (mean score 85.9/100) and low decisional conflict (mean score 20.9/100). Information content was rated adequate and sufficient, the therapy choices wording balanced, and presented without bias for a "best choice." Lower decisional conflict was associated with caregiver-reported anaphylaxis., Conclusions: This first pediatric OIT decision-aid, agnostic to product, allergen, and age has good acceptability, limited bias, and is associated with low decisional conflict and high decisional self-efficacy. It supports SDM in navigating the decision to start OIT or continue allergen avoidance., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Hypogammaglobulinemia is defined as a reduced immunoglobulin level, which can be either primary due to inborn errors of immunity or acquired in the setting of poor antibody production or increased antibody loss. Secondary hypogammaglobulinemia (SHG) should be considered in patients with a history of immunosuppressive therapy, transplant, protein loss syndromes, certain autoimmune conditions, and malignancies, as it can be associated with increased infectious risk. Appropriate history and lab-based screening in these populations can identify SHG allowing treatment and close monitoring as appropriate. Ideally, treatment focuses on control of the underlying condition or removal of iatrogenic causes of SHG. However, in many cases, treatment of the underlying condition does not reverse SHG or immunosuppressive therapy cannot be discontinued without significant risk to the patient. For these patients, strategies for risk mitigation against infectious complications include vaccination, antibiotic prophylaxis, and immunoglobulin replacement therapy. This report aims to summarize the existing and emerging data in the evaluation and management of SHG and highlight areas that require further investigation., Competing Interests: Disclosures Dr Lehman reports Clinical Trials for Navartis and Sanofi. Dr Mustafa reports speakers’ bureau positions at Genentech, Regeneron/Sanofi, AstraZeneca, GlaxoSmithKline, and CSL Behring and grants from Takeda. The other authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Penicillin allergy is reported in 5% to 15% of the world population, with 3% to 10% of pregnant women reporting the same. However, more than 90% of these patients can tolerate penicillin after appropriate evaluation. Penicillin is indicated for various issues that arise in pregnancy, and a history of allergy can have negative individual and public health consequences., Objective: Our aim was to prospectively evaluate the feasibility, safety, and select obstetric outcomes of obstetric penicillin allergy evaluations arranged through a direct referral phone line from obstetric practices to an employed allergy/immunology practice., Methods: Patients were referred via direct phone line for evaluation during their antenatal visits between May 2019 and May 2022. Patients underwent skin prick testing, and those with a negative penicillin skin testing (PST) result were subjected to amoxicillin challenge. In select cases of patients with a low-risk history, direct oral challenge was performed. Data were analyzed using descriptive statistics., Results: Of the 324 patients referred between May 2019 and May 2022, a total of 251 (77.5%) presented for in-office evaluations. Of those 251 patients, 239 (95.2%) underwent PST followed by oral challenge if the PST result was negative; 12 patients (4.8%) underwent direct challenge without skin testing, and all of them passed the challenge. Of the patients undergoing PST, 230 (97.2%) had a negative result and 229 tolerated subsequent oral amoxicillin doses, with 1 patient experiencing a delayed reaction to the amoxicillin. The group of patients who presented for evaluation included more people living in ZIP codes described as being of high socioeconomic status than in the no-show group (73.7% vs 63.3%)., Conclusion: To our knowledge, ours is the largest study to date to demonstrate the safety and feasibility of a phone line for obstetric penicillin allergy referrals. We demonstrate a better show rate than previous analyses, with most of the patients presenting for evaluation being successfully delabeled., Competing Interests: Disclosure of potential conflict of interest: S. S. Mustafa serves on the speakers bureau for Sanofi/Regeneron, AstraZeneca, GlaxoSmithKline, CSL Behring and has a grant from Takeda. A. Ramsey serves on the speakers bureau for Sanofi/Regeneron, AstraZeneca, and GlaxoSmithKline. The remaining author declares no relevant conflicts of interest., (© 2024 The Author(s).)

Competing Interests: Disclosures Dr Mustafa reports serving on the speakers bureau of Genentech, GlaxoSmithKline, AstraZeneca, and Regeneron/Sanofi and receiving grants from Takeda. Dr Ramsey reports serving on the speakers bureau of Sanofi/Regeneron, GlaxoSmithKline, and AstraZeneca. Dr Patrawala has no conflicts of interest to report.

Background: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians., Objective: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab., Methods: A systematic review of the literature was performed, and an expert Delphi Panel was assembled., Results: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective., Conclusion: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity., Competing Interests: Disclosures J.A.L. served as consultant for ARS, Aquestive, Bryn, ALK, and Novartis and Co-Chair Joint Task Force for Practice Parameters; received research money to institution from DBV and adjudication for Abvie and Siolta. T.E.D. the project described was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), under Award Number 2UL1TR001425 - 05A1; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. E.M.A. is and employee of Public Health Agency of Canada, but the views in any paper are her own and not those of Public Health Agency of Canada. Board member of the Canadian Society of Allergy and Clinical Immunology and Head of Allergy Section, Canadian Pediatric Society. A.A. received institutional funding (Novartis) and consultation/speaker fees (ALK, EPG Health, MJH, Adelphi, Genentech, FARE, and Medscape) and served as advisory board member (Ready, Set, Food; Novartis; and Genentech). K.G.B. received grants from NIH (R01AI150295), AHRQ (R01HS029319), and Thermo Fisher Scientific and royalties from UpToDate and is consulting for Denali Therapeutics. M.B. serves as investigator and advisory board member for Regeneron and Sanofi. N.M.C. serves as clinical investigator; received research support from AstraZeneca, Genentech, and Kenota Health; serves as advisor, consultant, and/or speaker for Amgen, ARS Pharma, AstraZeneca, Blueprint Medicines, Bryn Pharma LLC, Freed AI, Genentech, GSK, Hikma, Incyte, Novartis, Regeneron, and Sanofi. D.B.K.G. is a consultant for Novartis, Aquestive, CellDex, and Kokua; received clinical trials support from Genentech, Novartis, Pfizer, GSK, Merck, Regeneron, Allergy Therapeutics, Eli Lilly, and AstraZeneca and royalties from UpToDate. N.L.H. is a speaker for Adma Bio and Takeda; speaker and advisor for Pharming, Horizon/Amgen, Horizon; advisory board member and speaker for Pharmaceuticals/Amgen. M.G.L. received research money to institution from Regeneron. S.S.M. is speaker for Genentech, Regeneron/Sanofi, GSK, and AstraZeneca and received grant from Takeda. J.J.O. consultant/advisor: GSK, Aquestive, Amgen, and ARS; adjudication/DSMB: AZ, Novartis, GSK, Sanofi, and AbbVie; reviewer/editor and executive editor: Annals of Allergy, Asthma & Immunology; reviewer: UpToDate; executive editor: Medscape; research/grants: NIH. A.R. speakers bureau member for Sanofi/Regeneron, GSK, and AstraZeneca. N.L.R. received funding from the Jeffrey Modell Foundation (58293-I), the NIH (R21AI164100), and Takeda Pharmaceuticals; is consultant for Takeda, Pharming Healthcare, and CSL Behring; received royalties from Wolters Kluwer and UpToDate. L.S. is clinical investigator for Regeneron and DBV Technologies and advisor for Sanofi and Leo pharmaceuticals. M.S.S. is member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); has participated in research that has received funding from DBV. J.M.S. received grant support from and is consultant for Regeneron/Sanofi. C.A.S. recipient of a AAAAI Foundation Faculty Development Award. The views expressed in this work are the responsibility of the authors and do not necessarily represent the official views of the AAAAI. D.R.S. is consultant to ARS. J.W. received research support from NIAID, Aimmune, DBV Technologies, and Siolta and consultancy fees from ALK Abello, DBV Technologies, and Novartis. M.J.G. is consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology; is member of the Joint Taskforce on Allergy Practice Parameters; received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state/local allergy societies. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Shahzad Mustafa reports serving on the speakers bureau of Genentech, GlaxoSmithKline, AstraZeneca, and Regeneron/Sanofi and receiving grant from Takeda. Dr Anagnostou reports receiving institutional funding from Aimmune and Novartis; serving as advisory board member of Ready, set, food, Novartis; providing consultation and receiving speaker fees from ALK, EPG Health, MJH, Adelphi, Aimmune Therapeutics, and Genentech; and serving on FARE. Dr Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma & Immunology; and is member of the Joint Taskforce on Allergy Practice Parameters. He has received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, and multiple state/local allergy societies. Dr Lieberman is a member and co-chair of the Joint Task Force on Practice Parameters; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of the American Board of Allergy and Immunology; serves as an advisor consultant for ARS, Bryn, and Aquestive; serving on the adjudication/DSMB for AbbVie and Siolta; and is an investigator (money to institution) for Novartis and DBV. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV.

There are limited data on food allergies among college students. In this article, we review the most current available studies. These self-reported surveys and qualitative interviews reported overall poor avoidance of known allergens and low rates of carrying self-injectable epinephrine among students with food allergy. College students may exhibit risk-taking food behaviors due to a number of factors, including age-appropriate risk-taking predilection, strong social influences, and lack of experience in self-advocacy. Having to disclose an otherwise invisible condition repeatedly in a new environment may also lead to "disclosure fatigue," creating an additional barrier to self-advocacy. Common themes in the narrative include hypervigilance, stigma management, and concern about others' misunderstanding of food allergy. Although there is a paucity of data in this area, it is likely that having greater support at the institution level, along with support from peers and faculty, may help improve awareness, self-injectable epinephrine carriage, and allergen avoidance. This review also discusses strategies for preparedness at school, including specific steps to maximize safety., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pregnant individuals are at higher risk of complications from respiratory viruses such as coronavirus-19 disease (COVID-19). Altered lung function, vaccine hesitancy, and resistance to taking necessary medications because of a lack of safety data in pregnancy make this population especially vulnerable to the effects of COVID-19. Like many medical conditions, the treatment of allergic conditions, including asthma and allergic rhinitis, were affected during the pandemic, with decreased numbers of in-person visits and interruptions in medical treatment. There were initially no data to allow pregnant women with asthma know whether the condition put them at higher risk of complications from COVID-19. There are now increasing data for the efficacy and safety of vaccines for COVID-19 in at-risk populations, including pregnant women. Vaccine studies show no increased risk for spontaneous abortion, congenital anomalies, or pregnancy complications. Furthermore, infants of individuals vaccinated during pregnancy have been shown to obtain protective antibodies via the placenta, providing protection against COVID-19 after birth. Although overall risks are low, pregnant women who become infected with COVID-19 are at higher risk for maternal and pregnancy complications. Antiviral treatment is available for pregnant women with mild to moderate symptoms of COVID-19, with reassuring safety data to date. Dexamethasone is the mainstay of inpatient therapy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has evolved over the past 3+ years, and strategies to prevent illness and treat infection have changed over time. As COVID-19 transitions from a pandemic to an endemic infection, widespread nonpharmaceutical interventions such as mask mandates and governmental policies requiring social distancing have given way to more selective strategies for risk mitigation. Monoclonal antibody therapies used for disease prevention and treatment lost utility owing to the emergence of resistant viral variants. Oral antiviral medications have become the mainstay of treatment in nonhospitalized individuals, whereas systemic corticosteroids remain the cornerstone of therapy in those requiring supplemental oxygen. Emerging literature also supports the use of additional immune-modulating therapies in select admitted patients. Importantly, the COVID-19 pandemic highlighted both unprecedented research and development of medical interventions while also drawing attention to significant pitfalls in the global response. This review provides a comprehensive update in prevention and management of COVID-19., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Oral food challenge (OFC) remains the reference standard for food allergy (FA) diagnosis., Objective: This study reports a single-center observational experience with all OFCs conducted over 3 years., Methods: All OFCs performed at an outpatient office were tracked. The OFCs were conducted without strict prespecified inclusion or exclusion criteria. Demographic information along with results of diagnostic testing and results of the OFCs were recorded., Results: A total of 1132 OFCs were performed, with a median age of 4 years (interquartile range = 2.0-10.0). Of the 1132 OFCs, 862 (76.1%) tolerated the food, whereas 232 (20.5%) experienced a reaction, and 38 (3.4%) did not complete the OFC because of food refusal. The highest percentage of tolerated food was shellfish (91.1%), with the lowest percentage of tolerated food being baked egg (66.1%). There were 66 (5.8%) OFCs that were deemed to be high risk, of which 35 (53.0%) tolerated the food. More than 50% of reactions occurred on the first or second dose, with the most common clinical symptom being urticaria or angioedema, with 29.2% of reactions treated with epinephrine. There were several factors that predicted tolerating an OFC, including the food challenge, the reason for food avoidance, older age at the time of OFC and less reactive skin prick testing, and lower food-specific immunoglobulin E levels., Conclusion: Certain factors can predict tolerating an OFC, and even those considered to be high risk can be safely completed in an outpatient setting, with most tolerating the food, and most reactions not requiring treatment with epinephrine., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Secondary antibody deficiency (SAD) is a subtype of secondary immunodeficiency characterized by low serum antibody concentrations (hypogammaglobulinemia) or poor antibody function. SAD is common in patients with multiple myeloma (MM) due to underlying disease pathophysiology and treatment-related immune system effects. Patients with SAD are more susceptible to infections and infection-related morbidity and mortality. With therapeutic advancements improving MM disease control and survival, it is increasingly important to recognize and treat the often-overlooked concurrent immunodeficiency present in patients with MM. The aims of this review are to define SAD and its consequences in MM, increase SAD awareness, and provide recommendations for SAD management. Based on expert panel discussions at a standalone meeting and supportive literature, several recommendations were made. Firstly, all patients with MM should be suspected to have SAD regardless of serum antibody concentrations. Patients should be evaluated for immunodeficiency at MM diagnosis and stratified into management categories based on their individualized risk of SAD and infection. Infection-prevention strategy education, early infection reporting, and anti-infective prophylaxis are key. We recommend prophylactic antibiotics or immunoglobulin replacement therapy (IgRT) should be considered in patients with severe hypogammaglobulinemia associated with a recurrent or persistent infection. To ensure an individualized and efficient treatment approach is utilized, patient's immunoglobin G concentration and infection burden should be closely monitored throughout treatment. Patient choice regarding route and IgRT treatment is also key in reducing treatment burden. Together, these recommendations and proposed management algorithms can be used to aid physician decision-making to improve patient outcomes., Competing Interests: Disclosure SJ has received support for conferences, speaker, advisory boards, trials, data and safety monitoring boards, and projects with CSL Behring, Takeda, Swedish Orphan Biovitrum, Biotest, Binding Site, Grifols, BPL, Octapharma, LFB, Pharming, GSK, Weatherden, Zarodex, Sanofi, and UCB Pharma. SG has received research funding from Miltenyi Biotec, Takeda, Celgene, Amgen, Sanofi, Johnson and Johnson, and Actinium and is on the advisory boards for: Kite Pharmaceuticals, Celgene, Sanofi, Novartis, Johnson and Johnson, Amgen, Takeda, Jazz Pharmaceuticals, Actinium Pharmaceuticals and CSL Behring. TK has received support (never on a personal account) for conferences, speaker bureaus, advisory boards, trials, data and safety monitoring boards, and projects with Sanofi, Takeda, BMS, Johnson & Johnson, MSD, Novartis, Gilead, Octapharma and CSL Behring. HML has received consultancy fees and support for advisory boards from CSL Behring and Actinium Pharmaceuticals; is a member of the data safety and monitoring boards for BMS, BioSight, and Celgene; is a consultant, promotional speaker, and a member of the advisory boards for Jazz Pharmaceuticals and Seattle Genetics; is a promotional speaker for AstraZeneca; has received consultancy fees and has stock options with Partner Therapeutics; and has received consultancy fees from Pluristem. SM has received support for an advisory board and speaker bureaus with CSL Behring. GAP has received grants from Merck and Takeda and received support for advisory boards, data and safety monitoring boards, consultancy, speaker projects with Symbio, Merck, MSD, Allovir, Vera, Amplyx, Pfizer, Takeda, Cidara, Octapharma, Astellas and CSL Behring. RR has received support for advisory boards, data and safety monitoring boards, and speaker bureaus with Janssen Cilag, BMS, Celgene, Takeda, CSL Behring and Octapharma. DCV has received salary support from Fonds de Recherche du Québec - Santé Senior Clinician-Scientist scholar program; clinical trial support from CSL Behring, Cidara Therapeutics, Moderna, and Janssen; has received honoraria for advisory board consultations or speaker presentations from Astra Zeneca, GSK, Merck Canada, CSL Behring, Moderna, Novartis Canada, and UCB Biosciences GmbH; and has a patent application pending (Electronic Filing System ID: 40101099) and a report of invention submitted to McGill University (Track code: D2021-0043). JRW has received support for advisory boards and data and safety monitoring boards from CSL Behring, Cidara, Merck, Celgene, Ansun, and Takeda and royalties from UptoDate., (Copyright © 2023. Published by Elsevier Inc.)

Background: Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response., Methods: Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge., Results: Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kU A /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg)., Conclusions: Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships., (© 2023 DBV Technologies S.A. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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.)

This paper investigates the possibility to extend the cycle length of boiling water reactor bundles to 15 years of operation with three different burnable poisons; gadolinium, erbium, and boron carbide. This can be carried out by mixing highly enriched UO 2 fuel (15-19.9% U-235) with high concentrations of Gadolinium oxide (3-14% Gd 2 O 3 ) or Erbium oxide (2-4% Er 2 O 3 ).The boron carbide B 4 C was modeled as (Al 2 O 3 -B 4 C) rods in the bundle guide tubes. MCNPX code 2.7 was used to evaluate infinite multiplication factor (K-inf), power distribution, peaking factor, void reactivity coefficient, fuel cycle length, depletion of U-235, and fissile inventory ratio for the three designs at 40% void. The MCNPX simulation showed that introducing gadolinium rods at the bundle periphery has the advantage of lowering reactivity swing throughout the exposure range. The uniform distribution of erbium in all fuel rods contributed to the flattening of peaking factor at all the burnup stages. For the B 4 C design, the author found that the assembly with B 4 C-Al performs best in terms of reactivity flattening when five of the B 4 C-AL 2 O 3 rods are positioned in the central region of the assembly. Furthermore, the fuel temperature coefficient is more negative for gadolinium design at all burnup stages. On the other hand, the boron model delivers the lowest control rod worth. Finally, the moderator temperature coefficient is more negative for erbium and WABA designs due to the enhanced thermal neutrons capture by the effect of the strategic arrangement of WABA rods and the uniform distribution of erbium., (© 2023. The Author(s).)

Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background/objective: Although vaccination is the primary strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rheumatologic patients on B-cell depleting agent rituximab may have a suboptimal response. Tixagevimab and cilgavimab (Evusheld) could be administered under Food and Drug Administration emergency use authorization as pre-exposure prophylaxis., Methods: A cohort study of rheumatologic patients on rituximab therapy who received Evusheld was followed longitudinally. Adverse events were monitored., Results: Forty-three patients received Evusheld, with diagnoses including rheumatoid arthritis, ANCA vasculitis, immune-mediated myositis, Sjögren disease, and systemic lupus erythematosus. Average time to follow-up was 100 ± 33 days. One patient experienced symptomatic infection with SARS-CoV-2 confirmed by home antigen test twice. A total of 97.8% of patients during follow-up did not contract acute SARS-CoV-2 infection. At the same time, 32,074 new local cases were reported with a local cumulative SARS-CoV-2 incidence rate of 4.32%. Adverse events included myalgia, flu-like symptoms, fevers, injection site pain, or headache. No serious adverse events, anaphylaxis, or cardiac events occurred., Conclusions: Evusheld demonstrated effectiveness in preventing symptomatic SARS-CoV-2 infection in a real-world cohort of rheumatologic patients on rituximab therapy. Administration of Evusheld may be considered as part of a multilayered approach to risk mitigation in this high-risk population as pre-exposure prophylaxis., Competing Interests: A.J.O. has no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Patients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of secondary immunodeficiency (SID), SID-related infections, and mortality. Here, we report the results of a systematic literature review on the potential association of various cancer regimens with infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, indicative of SID., Methods: A systematic literature search was performed in 03/2022 using PubMed to search for clinical trials that mentioned in the title and/or abstract selected cancer (CLL, MM, or NHL) treatments covering 12 classes of drugs, including B-lineage monoclonal antibodies, CAR T therapies, proteasome inhibitors, kinase inhibitors, immunomodulators, antimetabolites, anti-tumor antibiotics, alkylating agents, Bcl-2 antagonists, histone deacetylase inhibitors, vinca alkaloids, and selective inhibitors of nuclear export. To be included, a publication had to report at least one of the following: percentages of patients with any grade and/or grade ≥3 infections, any grade and/or grade ≥3 neutropenia, or hypogammaglobulinemia. From the relevant publications, the percentages of patients with lymphocytopenia and specific types of infection (fungal, viral, bacterial, respiratory [upper or lower respiratory tract], bronchitis, pneumonia, urinary tract infection, skin, gastrointestinal, and sepsis) were collected., Results: Of 89 relevant studies, 17, 38, and 34 included patients with CLL, MM, and NHL, respectively. In CLL, MM, and NHL, any grade infections were seen in 51.3%, 35.9% and 31.1% of patients, and any grade neutropenia in 36.3%, 36.4%, and 35.4% of patients, respectively. The highest proportion of patients with grade ≥3 infections across classes of drugs were: 41.0% in patients with MM treated with a B-lineage monoclonal antibody combination; and 29.9% and 38.0% of patients with CLL and NHL treated with a kinase inhibitor combination, respectively. In the limited studies, the mean percentage of patients with lymphocytopenia was 1.9%, 11.9%, and 38.6% in CLL, MM, and NHL, respectively. Two studies reported the proportion of patients with hypogammaglobulinemia: 0-15.3% in CLL and 5.9% in NHL (no studies reported hypogammaglobulinemia in MM)., Conclusion: This review highlights cancer treatments contributing to infections and neutropenia, potentially related to SID, and shows underreporting of hypogammaglobulinemia and lymphocytopenia before and during HM therapies., Competing Interests: Literature searches, article screening, data abstraction, and medical writing support was provided by Meridian HealthComms Ltd (Manchester, UK) in accordance with Good Publication Practice guidelines and funded by CSL Behring. SJ has received support for conferences, speaker, advisory boards, trials, data and safety monitoring boards, and projects with CSL Behring, Takeda, Swedish Orphan Biovitrum, Biotest, Binding Site, Grifols, BPL, Octapharma, LFB, Pharming, GSK, Weatherden, Zarodex, Sanofi, and UCB Pharma. SG has received research funding from Miltenyi Biotec, Takeda, Celgene, Amgen, Sanofi, Johnson and Johnson, and Actinium and is on the advisory boards for: Kite Pharmaceuticals, Celgene, Sanofi, Novartis, Johnson and Johnson, Amgen, Takeda, Jazz Pharmaceuticals, Actinium Pharmaceuticals, and CSL Behring. TK has received support, never on a personal account, for conferences, speaker bureaus, advisory boards, trials, data and safety monitoring boards, and projects with Sanofi, Takeda, BMS, Johnson & Johnson, MSD, Novartis, Gilead, Octapharma, and CSL Behring. HML has received consultancy fees and support for advisory boards from CSL Behring and Actinium Pharmaceuticals; is a consultant, promotional speaker, and a member of the advisory boards for Jazz Pharmaceuticals and Seattle Genetics; is a member of the data safety and monitoring boards for BMS, BioSight, and Celgene; is a promotional speaker for AstraZeneca; has received consultancy fees and has stock options with Partner Therapeutics; and has received consultancy fees from Pluristem. SSM has received support for an advisory board and speaker bureaus with CSL Behring. RR has received support for advisory boards, data and safety monitoring boards, and speaker bureaus with Janssen Cilag, BMS, Celgene, Takeda, CSL Behring, and Octapharma. DCV has received salary support from Fonds de Recherche du Québec - Santé Senior Clinician-Scientist scholar program; has received clinical trial support from CSL Behring, Cidara Therapeutics, and Moderna; has received honoraria for advisory board consultations or speaker presentations from Astra Zeneca, CSL Behring, Merck Canada, Moderna, Novartis Canada, Qu biologics, and UCB Biosciences GmbH; and has a patent application pending Electronic Filing System ID: 40101099 and a report of invention submitted to McGill University Track code: D2021-0043., (Copyright © 2023 Jolles, Giralt, Kerre, Lazarus, Mustafa, Ria and Vinh.)

Secondary immunodeficiency (SID) in patients with B-cell hematological malignancies is a common condition that presents with recurrent infection. SID is due to both the inherent immune defects due to the malignancy, as well as secondary to cancer therapies, many of which have B-cell depleting properties. The early diagnosis of SID and the optimization of intervention strategies are key to delivering the most effective cancer treatments and reducing infection-related morbidity and mortality. This review discusses current practice, recommendations, and challenges for SID diagnosis, based on the evaluation of clinical history and laboratory assessments, and the effectiveness of specific vaccines and immunoglobulin replacement therapy in reducing the frequency and recurrence of infections in patients with SID, and the healthcare system-associated costs., Competing Interests: Conflict of interest statement NS has received research funding from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, and Nektar; and reports advisory role for GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, and Oncopeptides. SSM reports speaker’s bureau for Genentech, GSK, Regeneron, AstraZeneca, and CSL Behring. DCV has received clinical trial support from CSL Behring, Cidara Therapeutics, and Janssen Pharmaceuticals; has received honoraria for advisory board consultations or speaker presentations from Merck Canada, CSL Behring, Novartis Canada, and UCB Biosciences GmbH; and has a patent application pending (Electronic Filing System ID: 40101099) and a report of invention submitted to McGill University (Track code: D2021–0043)., (Copyright © 2022. Published by Elsevier B.V.)

Objective/background: In the era of novel agents, Bruton tyrosine kinase (BTK) inhibitors have changed the dynamics of treating chronic lymphocytic leukemia. However, small studies have shown conflicting results regarding the additive humoral dysfunction with their use., Methods: We prospectively compared vaccine responses in patients on ibrutinib (n = 10) with matched controls (n = 16) and analyzed whether a protein-based (tetanus-diphtheria toxoid) or a carbohydrate (Pneumovax) moiety will result in an improved immunological response., Results: An appropriate serological response in IgG titers for diphtheria was seen in 40% of patients on ibrutinib and 31% of patients in the control group. About 30% of patients on ibrutinib and 44% of patients in the control group had an adequate response to tetanus toxoid. None of the patients on ibrutinib mounted an adequate response to Pneumovax, while 31% of patients in the control arm responded appropriately. These differences in the results were considered insignificant as all p values were greater than the cut-off of 0.05., Conclusion: Our study did not show significant detrimental vaccine responses with ibrutinib and calls for larger multicenter studies to elucidate long-term effects, especially in patients with prior exposure to anti-CD20 monoclonal antibodies.

Background: Immunocompromised individuals with hematological malignancy have increased risk for poor outcomes and death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This special population may mount a suboptimal response to vaccination. We assessed the effectiveness of tixagevimab and cilgavimab (Evusheld), a monoclonal antibody combination against SARS-CoV-2, in conjunction with standard preventative measures, at preventing symptomatic incident infection., Methods: Patients aged 18 years and older with hematological malignancy consented to receive Evusheld. Patients were followed longitudinally for development of symptomatic incident SARS-CoV-2 infections. Adverse events were monitored., Results: Two hundred and three patients (94 female) with hematological malignancies and mean age 72 ± 10 years were included. Of the patients, 99.5% had received at least one mRNA vaccination against SARS-CoV-2. Average time of follow-up was 151 ± 50 days. Nineteen patients (9.3%) developed incident symptomatic SARS-CoV-2 infection, with only one (0.5%) requiring hospitalization. During the same follow-up period, local incident rate of infection was 84,123 cases (11.3% of population). Of those, 3,386 cases (4%) of SARS-CoV-2 required hospital admission. The incidence rate ratio was 0.79. No serious adverse events occurred following administration of Evusheld., Conclusion: Patients with hematological malignancy who received Evusheld infrequently developed symptomatic infections or require hospitalization. The high-risk cohort incidence was at least as comparable to the average risk general population. Evusheld appears effective and is well tolerated, and may be administered in conjunction with vaccination and standard prevention measures, at decreasing incident SARS-Co-V2 cases in this high-risk population., Competing Interests: AJO, KEO, JB, SKL, NN, HS have no financial conflict of interest. SSM reports speaker’s bureau: Genentech, Regeneron/Sanofi, GSK, AstraZeneca, CSL Behring, Aimmune. SJ reports speaker’s bureau for Takeda and received honoraria from Bristol Meyers Squibb., (Copyright 2022, Ocon et al.)

Individuals with primary immunodeficiency (PIDD) experience not only infectious complications but also immune dysregulation leading to autoimmunity, inflammation, and lymphoproliferative manifestations. Management of these complications often requires treatment with additional immunosuppressive medications, which pose an additional risk of infectious complications. Immunosuppression in individuals with PIDD therefore requires careful assessment and consideration of risks and benefits. Medications should be closely monitored, and strategies for risk mitigation of adverse events considered, such as exposure reduction, appropriate vaccination, use of antibiotics/antivirals, and optimization of immunoglobulin replacement therapy. In a subset of individuals who are not tolerating immune modulation or experiencing disease progression despite appropriate interventions, hematopoietic stem-cell transplantation is a management option., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Outdoor air pollution is associated with exacerbations of allergic diseases, including asthma, allergic rhinitis, and other atopic conditions. The increased allergic disease prevalence has been linked to this urbanization, industrialization, and economic growth globally. Air pollutants are well-known to disrupt the epithelium leading to specific diseases in any organ system that has epithelial linings. This review provides an overview of the health effects of air pollution on allergic disorders and specifically addresses how it may impact the epithelial barrier in the upper and lower respiratory tracts to facilitate the health effects associated with these exposures., Competing Interests: Conflicts of interest A. Nanda: None. S.S. Mustafa: Genentech, Regeneron/Sanofi, GSK, AstraZeneca, CSL Behring, Aimmune. M. Castillo: None. J.A. Bernstein: INEOS; Speaking: Sanofi-Regeneron, AZ, GSK, Novartis, Genentech, Takeda/Shire, CSL Behring, Biocryst, Pharming, Optinose; Research and consultant: Sanofi-Regeneron, AZ, GSK, Novartis, Genentech, Takeda/Shire, CSL Behring, Biocryst, Pharming, Kalvista, IONIS, Celldex, TLL, ONO, Escient, Cycle, Blueprint Medicine, Biomarin, Merck, Amgen., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Important components of drug safety, efficacy, and acceptability involve manufacturing and testing of the drug substance and drug product. Peanut flour sourcing/processing and manufacturing processes may affect final drug product allergen potency and contamination level, possibly impacting drug safety, quality, and efficacy. We describe key steps in the manufacturing processes of peanut ( Arachis hypogaea ) allergen powder-dnfp (PTAH; Palforzia®), a drug used in oral immunotherapy (OIT) for the treatment of peanut allergy., Methods: Established criteria for source material must be met for manufacturing PTAH drug product. Degree of roasting was determined with a Hunter colorimeter. Protein/allergen content, identity, potency, safety, and quality of each batch of PTAH drug substance were assessed with a combustion analyzer, allergen-specific Western blot (immunoblotting), ELISA, and HPLC. Contaminants (ie, aflatoxin) were measured by UPLC., Results: Roasting degree beyond "light roast" was associated with variable degrees of protein allergen degradation, or potentially aggregation. Relative potency and amounts of protein allergens showed variability due in part to seasonal/manufacturing variability. Proportion of lots not meeting aflatoxin limits has increased in recent years. Up to 60% of peanut flour source material failed to meet screening selection acceptance criteria for proceeding to drug substance testing, mostly because of failure to meet potency acceptance criteria. Other lots were rejected due to safety (ie, aflatoxin) and quality. Influence of potency variation, within specification parameters, on safety/tolerability observed in trials was considered low, in part due to stringent controls placed at each step of manufacturing., Conclusions: Extensive variability in allergen potency is a critical issue during immunotherapy, particularly during OIT initial dose escalation and up-dosing, as it may result in lack of efficacy or avoidable adverse allergic reactions. Based on EU and US regulatory requirements, the production of PTAH includes manufacturing controls to ensure drug product safety, potency, and quality. For example, although PTAH contains all peanut allergens, each lot has met strict criteria ensuring consistent allergenic potency of Ara h 1, Ara h 2, and Ara h 6. The rigor of PTAH's manufacturing process ensures reliable dose consistency and stability throughout its shelf life., Competing Interests: Stephanie A. Leonard reports being a consultant for Aimmune Therapeutics, a Nestlé Health Science company, DBV Technologies, and Cour Pharmaceuticals Development Co., Inc, a member of the International FPIES Association medical advisory board, a speaker for Aimmune Therapeutics, a Nestlé Health Science company, and a site investigator for Aimmune Therapeutics, a Nestlé Health Science company, and DBV Technologies. Yasushi Ogawa is an employee of Aimmune Therapeutics, a Nestlé Health Science company. Paul T. Jedrzejewski is an employee of Aimmune Therapeutics, a Nestlé Health Science company. Soheila J. Maleki has no disclosures to report. Martin D. Chapman reports an R01 research grant on the structural biology of allergens from NIH NIAID. In addition, they report honorarium for molecular allergology symposium from Johns Hopkins University and is a co-owner and shareholder of InBio. Stephen A. Tilles is an employee of Aimmune Therapeutics, a Nestlé Health Science company. George Du Toit reports research grants to their institution and advisory board fees from Aimmune Therapeutics, a Nestlé Health Science company. S. Shahzad Mustafa reports honoraria for Aimmune program. Brian P. Vickery reports advisory board/consultant for Aimmune Therapeutics, AllerGenis, FARE, Reacta; site investigator for Aimmune Therapeutics, a Nestlé Health Science company, DBV, Genentech, Regeneron; and research grants from FARE and NIAID., (© 2022 Leonard, Ogawa, Jedrzejewski, Maleki, Chapman, Tilles, Du Toit, Mustafa and Vickery.)

The use of telemedicine has increased in allergy/immunology, with rapid uptake of its use during the coronavirus disease 2019 pandemic. Existing data indicate an overall positive view of telemedicine by patients, particularly during the coronavirus disease 2019 pandemic. However, patients and clinicians prefer in-person visits for specific types of allergy/immunology encounters, such as those requiring a physical examination or diagnostic testing. The most data for telemedicine exist with asthma, and provide a model for treatment technique, therapeutic monitoring, and education in other allergic and immunologic conditions. Clinician satisfaction is also necessary for telemedicine to be an enduring option for patient/clinician interactions, and this is influenced by a multitude of factors, including technology quality, reimbursement, and maintenance of patient/clinician relationships. Areas of future research should include the need for more outcome data in additional disease states, which will likely help facilitate improved logistical policies around telemedicine that would facilitate its adoption., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Shared learnings from the early use of novel therapies can aid in their optimization. The recent introduction of peanut oral immunotherapy (peanut OIT; Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp]) for peanut allergy addresses a significant unmet need but also highlights the requirement for consideration of several factors by both prescribers and patients., Objective: To provide guidance for prescribers of licenced peanut OIT to facilitate treatment delivery and improve outcomes., Methods: Clinicians with experience of licenced peanut OIT (United States n = 6, United Kingdom n = 1) participated in a series of interviews and group discussions designed to elicit tips for successful implementation., Results: Clinicians identified 8 tips that were considered the most relevant, practical, and impactful for prescribers of Peanut (Arachis hypogaea) Allergen Powder-dnfp: (1) preparing to provide treatment, (2) assessing the medical indication for treatment and (3) shared decision making, (4) staff education, (5) establishing office processes, (6) managing patient expectations and using anticipatory guidance, (7) optimising adherence and (8) maintaining flexibility throughout the treatment process. In addition, a range of supporting materials (e.g., checklists and action plans) are provided., Conclusion: The introduction of a novel therapy often requires healthcare providers to modify or adopt practices to effectively employ the treatment. The provision of guidance based upon early real-world experiences of licenced peanut OIT may help inform clinical practice and improve treatment outcomes., (© 2022. The Author(s).)

Purpose of Review: There are multiple FDA-approved biologics to treat poorly controlled moderate-to-severe asthma. Given the heterogeneity of asthma and the lack of head-to-head data between biologics, selecting the best biologic for a patient can be difficult. This review summarizes the key literature to date, in hopes of facilitating an evidence-based approach to selecting the most appropriate biologic for patients with asthma., Recent Findings: In addition to unique mechanisms of action, there is increasing literature on predictors of response to each biologic, such as sensitizations to aeroallergens, peripheral eosinophil count, total serum IgE, and exhaled nitric oxide. Biologics available for asthma are also being increasingly studied in comorbid conditions with asthma, and this may facilitate selecting the most appropriate biologic for a patient. In the absence of head-to-head studies, there is literature of switching between biologics whenever necessary., Summary: The authors outline an approach to selecting a biologic based on various considerations, and hope this suggested approach facilitates selecting the biologic most suitable for each individual with poorly controlled moderate-to-severe asthma., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate whether first-episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes., Methods: This is a randomized controlled single-blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3-year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well-known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3-year period., Results: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying., Conclusion: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one-third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high-school completion may be additional avenues for targeting functional recovery., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population., Patients and Methods: Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks., Results: Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG., Conclusions: Patients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs., Clinical Trials Registration: NCT03730129., Competing Interests: The authors have read the journal’s policy and have the following competing interests: CSL Behring provided support for this study in the form of an investigator-initiated grant awarded to SSM. SSM is on the speaker’s bureau for CSL Behring, Genentech, Regeneron, and AstraZeneca. AR is on the speaker’s bureau for Regeneron. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

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.)

In this work, SiC (Silicon carbide), FeCrAl (ferritic), SS-310 (stainless steel 310) and Zirconium are simulated by MCNPX (Monte Carlo N-Particle eXtended) code as cladding materials in advanced PWR (Pressurized Water Reactor) assembly. A number of reactor safety parameters are evaluated for the candidate cladding materials as reactivity, cycle length, radial power distribution of fuel pellet, reactivity coefficients, spectral hardening, peaking factor, thermal neutron fraction and delayed neutron fraction. The neutron economy presented by Zr and SiC models is analyzed through the burnup calculations on the unit cell and assembly levels. The study also provided the geometric conditions of all cladding materials under consideration in terms of the relation between fuel enrichment and cladding thickness from the viewpoint to achieve the same discharge burnup as the Zircaloy cladding. It was found that the SiC model participated in extending the life cycle by 2.23% compared to Zr. The materials other than SiC largely decreased discharge burnup in comparison with Zircaloy. Furthermore, the claddings with lower capture cross-sections (SiC and Zr) exhibit higher relative fission power at the pellet periphery. The simulation also showed that using SiC with a thickness of 571.15 μm and 4.83% U-235 can satisfy the EOL irradiation value as Zr. For reactivity coefficient, the higher absorbing materials (SS-310 and FeCrAl) exhibit more negative FTCs, MTCs and VRCs at the BOL But, at the intermediate stages of burnup Zr and SiC have a strong trend of negative reactivity coefficients. Finally, the delayed neutron fraction of SiC and Zr models is the highest among all the four models., (© 2021. The Author(s).)