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We report a case of a malignant fibrous histiocytoma (MFH) of the aortic bifurcation, which manifested as a pseudoaneurysm with the formation of an ilio-caval fistula, a complication about which, to our knowledge, nothing has been published previously. Spiral CT, catheter arteriography and venography were complementary in the diagnostic procedure. [ABSTRACT FROM AUTHOR]

Abstract Background The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral genome generates a reference for understanding the limits to viral escape, and can serve as a template for the discovery of sites of genetic conflict with known or unknown host proteins. Results To build a thorough evolutionary, functional and structural map of the HIV-1 genome, complete subtype B sequences were obtained from the Los Alamos database. We mapped sites under positive selective pressure, amino acid conservation, protein and RNA structure, overlapping coding frames, CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA dinucleotide motives. Globally, 33% of amino acid positions were found to be variable and 12% of the genome was under positive selection. Because interrelated constraining and diversifying forces shape the viral genome, we included the variables from both classes of pressure in a multivariate model to predict conservation or positive selection: structured RNA and α-helix domains independently predicted conservation while CD4 T cell and antibody epitopes were associated with positive selection. Conclusions The global map of the viral genome contains positive selected sites that are not in canonical CD8 T cell, CD4 T cell or antibody epitopes; thus, it identifies a class of residues that may be targeted by other host selective pressures. Overall, RNA structure represents the strongest determinant of HIV-1 conservation. These data can inform the combined analysis of host and viral genetic information.

In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N -linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N -linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N -linked glycosylation as well as the broader scientific community.

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a T H 2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy., Competing Interests: Disclosures Dr Ciaccio receives research grant support from the National Institutes of Health (NIH), Food Allergy Research & Education (FARE), and Paul and Mary Yovovich and has served as a medical consultant/advisor for Genentech, Novartis, Siolta, Clostrabio, and FARE. Dr Chinthrajah reports receiving grants from National Institute of Allergy and Infectious Diseases (NIAID), CoFAR, Regeneron, Stanford Maternal and Child Health Research Institute, and FARE and is an advisory board member at Alladapt Therapeutics, Novartis, Genentech, Allergenis, Intrommune Therapeutics, and IgGenix. Dr Chan reports receiving grant from NIAID and NIH. Prof Leung reports receiving grants from Genentech, Incyte Corporation, and Sanofi-Genzyme; nonfinancial support from Aslan Pharmaceuticals; and personal fees from Leo Pharmaceuticals. Dr Marshall reports receiving research grant support from NIH. Prof Nadeau reports receiving grants from NIAID; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Environmental Health Sciences (NIEHS); and FARE; receiving stock options from IgGenix, Seed Health, ClostraBio, Cour, and Alladapt; serving as an advisor at Cour Pharma; serving as a consultant for Excellergy, Red tree ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; serving as a co-founder of Before Brands, Alladapt, Latitude, and IgGenix; serving as National Scientific Committee member at Immune Tolerance Network (ITN) and NIH clinical research centers; and having patents including, “Mixed allergen composition and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” Dr Radulovic reports receiving grant from NIAID and NIH. Prof Lack reports receiving grant from NIAID/NIH; having personal fees and stock options from DBV Technologies; having stock options from Mission MightyMe; and serving as a scientific consultant/advisor for Novartis, Sanofi-Genzyme, Regeneron, ALK-Abello, Reckitt Mead Johnson, and Lurie Children's Hospital. Dr Sindher receives research grant support from NIH, FARE, CoFAR, DBV, AIMMUNE, and Regeneron and has served as an advisor for Genentech. Prof Brough reports receiving grant from NIAID and NIH and receiving speaker honoraria from DBV Technologies, GlaxoSmithKline, and Sanofi. The remaining authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption., Methods: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months., Results: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 μg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 μg/l. Adverse events were uncommon, and the majority were related to the food challenge., Conclusions: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).

A review of the latest publications in food allergy over the past couple of years confirmed that food allergy is a major public health concern, affecting about 8% of children and 10% of adults in developed countries. The prevalence of food allergy varies around the world, with the increase being driven mainly by environmental factors, possibly together with genetic susceptibility to environmental changes. A precise diagnosis of food allergy is extremely important. Both new tests (eg, the basophil activation test) and improved optimization of information provided by existing tests (eg, the skin prick test and measurement of specific IgE level) can contribute to improving the accuracy and patients' comfort of food allergy diagnosis. Understanding the underlying immune mechanisms is fundamental to designing allergen-specific treatments that can be safe and effective in the long term. New discoveries of the immune response to food allergens, including T-cell and B-cell responses, have emerged. Novel therapeutic approaches are being trialed at various stages of development as attempts to allow for more active intervention to treat food allergy. Prevention is key to reducing the increase in prevalence. Early introduction of allergenic foods seems to be the most effective intervention, but others are being studied, and will, it is hoped, lead to modification of the epidemiologic trajectory of food allergy over time., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many children are consuming some egg when they are diagnosed with egg allergy. We hypothesized that egg consumption could modify the diagnostic performance of allergy tests., Objective: To stratify diagnostic performance of tests according to egg consumption status., Methods: The BAT2 study (NCT03309488) participants underwent oral food challenge (OFC), food-frequency questionnaires, skin prick test (SPT), specific immunoglobulin E (sIgE) and specific immunoglobulin G4 (sIgG4) and basophil activation test (BAT)., Results: At study entry, 45% of participants reported partial egg consumption ("consumers") and 55% were avoiding egg strictly ("avoiders"). Avoiders had larger SPT (P < .001), higher BAT to egg (P < .001), sIgE to egg white (EW; P = .001) and to ovalbumin (OVA; P = .001), but not to ovomucoid (P = .231). Consumers had higher levels of sIgG4 to all egg allergens (P < .001) than avoiders. In consumers, the test with the best diagnostic performance was BAT (area under the curve [AUC] = .912) followed by SPT to raw egg (AUC = 0.805), EW-sIgE (AUC = 0.738), and OVA-sIgE (AUC = 0.732). In avoiders, the best tests were BAT (AUC = 0.834) and EW-sIgE (AUC = 0.833) followed by OVA-sIgE (AUC = 0.793) and SPT to EW (AUC=0.789). Using 100% sensitivity and 100% specificity cut-offs, the proportion of patients requiring OFC were 33% for BAT, 53% for SPT to raw egg, 61% for OVA-sIgE, and 73% for EW-sIgE for consumers; and 73% for BAT, 79% for EW-sIgE, and 93% for SPT to EW for avoiders., Conclusions: The diagnostic performance of tests is influenced by the immunomodulatory effect of egg consumption. BAT is the most reliable test and reduced the need for OFC, particularly in partial egg consumers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg., Methods: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC., Results: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non-severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid-sIgE (p = .009) and higher BAT to BE (p = .001). Patients with lower threshold to BE had higher IgE-specific activity (p = .027) and BAT to egg (p = .007) but lower severity score (p = .008). Optimal cut-offs for ovomucoid-sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut-offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients., Conclusions: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Air pollution is a current major health issue. The burden of airborne pollutants and aeroallergen levels varies throughout the year, as well as their interaction and consequences. Prenatal exposure during pregnancy has been associated with adverse perinatal outcomes. The aim of this study was to evaluate the impact of air pollutants on perinatal outcomes in patients with or without respiratory allergy., Material and Methods: Nested case-control retrospective study on 3006 pregnant women. Correlations between concentrations of common pollutants in each trimester of pregnancy and on average during the whole pregnancy and both gestational age at delivery and birthweight were studied. Pearson's correlation coefficient and binary logistic regression were used., Results: In general, pollutants correlated more strongly with birthweight than with gestational age at delivery. Nine-month NO 2 , SO 2 , CO, and benzene, and second-trimester CO negatively correlated with birthweight, whereas only first-trimester NO 2 showed a very mild correlation with gestational age at delivery. Negative correlations between pollutants and birthweight were much stronger in the respiratory allergy group (n = 43; 1.4%) than in the non-allergic group. After adjustments, the most significant predictive pollutant of birthweight was SO 2 in both groups. The best predictive model was much stronger in the allergic group for third-trimester SO 2 (R 2  = 0.12, p = 0.02) than in the non-allergic group for total SO 2 (R 2  = 0.002, p = 0.02). For each unit that SO 2 increased, birthweight reduced by 3.22% vs. 1.28% in each group, respectively., Conclusions: Air pollutant concentrations, especially SO 2 , negatively influenced birthweight. The impact of this association was much stronger and more relevant in the group of women with respiratory allergies., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Double-blind placebo-controlled food challenges (DBPCFC) are the gold-standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE)., Methods: Children aged 6 months to 15 years were assessed for possible egg allergy as part of the BAT2 study (NCT03309488). They underwent clinical assessment, skin prick test (SPT), specific IgE (sIgE) and basophil activation test (BAT). The results of the tests were compared with DBPCFC outcomes to both BE and LCE., Results: A total of 150 children underwent DBPCFC to BE, 60 (40%) reacted to and 85 (57%) tolerated BE and 5 (3%) had inconclusive oral food challenges (OFC). Seventy-seven children tolerant to BE had DBPCFC to LCE and 16 reacted. The test within each modality with the best diagnostic performance for BE allergy was as follows: SPT to egg white (EW) (AUC = 0.726), sIgE to EW (AUC = 0.776) and BAT to egg (AUC = 0.783). BAT (AUC = 0.867) was the best test in the younger than 2 years age group. Applying 100% sensitivity and 100% specificity cut-offs, followed by OFC, resulted in 100% diagnostic accuracy. BAT enabled the greatest reduction in OFC (41%). Using sIgE followed by BAT allowed to reduce the number of BATs performed by about 30% without significantly increasing the number of OFC., Conclusions: The best diagnostic test was BAT to egg in terms of diagnostic accuracy and reduction in number of OFC. Using sIgE to EW followed by BAT required fewer BATs with sustained OFC reduction and diagnostic accuracy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

HIV-1 remains a global health crisis 1 , highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa 2 , we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV 3 . We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log 10 -transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair 4 . Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist., Methods: HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions?, Results: This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected., Conclusion: This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic., Competing Interests: The views expressed are solely those of the authors and do not necessarily represent those of the U.S. Department of Health and Human Services. Timothy Bergquist, Tellen Bennett, and Richard Moffitt disclosed that this work was performed by Sage Bionetworks and its subcontractors under a grant with the National Institute of Health (U24TR002306). Additional funding for Timothy Bergquist was provided through the Bill and Melinda Gates Foundation (INV- 018455). Marie Wax and Hui-Hsing Wong disclose that they are government support contractors employed by Aveshka Inc. and Tunnell Government Services Inc. respectively, which receives funds from the U.S. government under contract to provide technical and programmatic support for HHS-BARDA. Joy Alamgir discloses that he is a founder and a shareholder of ARIScience. Tellen Bennett has received funding from the National Institutes of Health – NCATS, Eunice Kennedy Shriver NICHD, and National Heart, Lung and Blood Institute (NHLBI)., (© The Author(s) 2023.)