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Food allergy is a substantial public health concern associated with risk of severe or potentially life-threatening reactions and requiring life-altering changes in dietary habits. This increasingly prevalent health concern is associated with adverse medical, nutritional, psychosocial, and economic effects on the estimated 32 million affected individuals in the United States. Management of food allergy requires life-altering dietary modifications and constant vigilance to avoid implicated allergens to minimize the risk of anaphylaxis, which can lead to considerable anxiety and reduced quality of life. Specialized diets are expensive and often difficult to access, particularly for low-income and minority individuals with food allergy. The overlap of food insecurity with diet-treated illnesses further increases the burden on patients with food allergies and their families, with overall rates of food insecurity increasing substantially during the coronavirus disease 2019 pandemic. Universal screening to identify food insecure households and connect them with appropriate resources is a critical step in addressing unmet needs at the individual and family level. At the systems level, integrated advocacy approaches addressing the complex interplay between multiple societal issues such as poverty, systemic racism, wage inequality, housing insecurity, lack of transportation, and other social determinants of health are vital to ensure access to safe, healthy, nutritionally complete options for patients with food allergies and their families.

BACKGROUND AND AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n=27) and controls (normal [NL, n=20], Crohn disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r=0.78 and 0.77, P < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response compared with other EGIDs. Decreased cell-cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSION: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis and eosinophilic gastritis in a geographically diverse cohort of patients compared to controls.We conducted a prospective study of individuals with eosinophilic gastrointestinal disease in the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative PCR. Community composition was determined by small subunit rRNA gene amplicons.139 mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased (Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE (Streptococcus, Gemella) and EoG (Leptotrichia), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability amongst individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls.Dominant community members (Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS.

The concepts of diversity, equity, and inclusion are fundamental and more recently heavily discussed within medicine, research, and the larger society. There is increasing awareness that diversity of thoughts, perspectives, and backgrounds yields stronger teams and more effective results. There is also increasing awareness that stark inequities from systemic, institutional, and individual levels exist that limit the baseline opportunities for many populations. To close disparity gaps, broad aspects of diversity and promoting equity are required and efforts must be inclusive of those most marginalized. In this Clinical Commentary, we discuss, "How and If progress has been made in Diversity, Equity, Inclusion within the field of Allergy/Asthma/Immunology in the past decade?" We discuss the current state of clinical practice and what has been revealed over the past 10 years; describe our current workforce and what progress has or has not occurred there; and finally, review the state of scientific and medical research.

Health disparities are health differences linked with economic, social, and environmental disadvantage. They adversely affect groups that have systematically experienced greater social or economic obstacles to health. Renewed efforts are needed to reduced health disparities in the United States, highlighted by the disparate impact on racial minorities during the coronavirus pandemic. Institutional or systemic patterns of racism are promoted and legitimated through accepted societal standards, and organizational processes within the field of medicine, and contribute to health disparities. Herein, we review current evidence regarding health disparities in allergic rhinitis, asthma, atopic dermatitis, food allergy, drug allergy, and primary immune deficiency disease in racial and ethnic underserved populations. Best practices to address these disparities involve addressing social determinants of health and adopting policies to improve access to specialty care and treatment for the underserved through telemedicine and community partnerships, cross-cultural provider training to reduce implicit bias, inclusion of underserved patients in research, implementation of culturally competent patient education, and recruitment and training of health care providers from underserved communities. Addressing health disparities requires a multilevel approach involving patients, health providers, local agencies, professional societies, and national governmental agencies.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy that can involve the temporomandibular joint. It is known to accelerate the osteoarthritic process, often initially presenting with advanced level of disease. The management of CPPD in the rheumatology and orthopedic literature is one of early diagnosis and medical management of acute attacks. The cases of three patients who presented with initial complaints of joint pain and limited mouth opening are presented. Preoperative imaging identified calcifications in two of these patients. Definitive diagnosis was achieved through arthroscopic-assisted biopsy. Rheumatology referrals revealed chondrocalcinosis of the knee in one patient. All patients had improved mouth opening and pain.

Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE-mediated food allergy that primarily affects the gastrointestinal tract. The underlying pathophysiology of FPIES has yet to be fully elucidated; however, FPIES is believed to be secondary to intestinal inflammation after exposure to a food antigen, which thereby leads to increased permeability and fluid shifting into the intestinal lumen. FPIES is categorized into acute and chronic forms. Acute FPIES is characterized by repetitive vomiting that occurs 1‐4 hours after food ingestion. Severe vomiting may progress to dehydration, lethargy, and pallor, which potentially leads to hypovolemic shock. In some patients, diarrhea may present within 24-hours of food ingestion. Patients are clinically well between acute episodes. Chronic FPIES presents with intermittent vomiting and/or diarrhea, followed by failure to thrive. FPIES characteristically presents in infancy, with resolution of the disease typically occurring by school age. However, analysis of recent data indicates that FPIES may persist into adulthood. In addition, late- or adult-onset FPIES has also been reported. The diagnosis of FPIES is based on clinical history; however, oral food challenge currently remains the criterion standard for diagnosis. Management of FPIES requires strict avoidance of food triggers, and treatment requires rapid fluid rehydration. Currently, there are no reliable biomarkers to diagnose FPIES; however, investigations to better understand the role of the innate immune system have been promising. Future studies are needed to better understand the true prevalence and pathophysiology of FPIES.

Background Food allergies are becoming a global concern and pose a significant burden on allergic children and their family, with reported physical and emotional effects. Objective To investigate the effect of food allergy on patients′ quality of life (QoL), to identify any characteristics associated with worse QoL, and to directly compare the effect of food allergies on the QoL of adolescents vs younger children. Methods Children 0 to 17 years old with a physician-confirmed food allergy diagnosis were invited to participate by completing the validated Food Allergy Quality of Life Questionnaire (FAQLQ). The FAQLQ form for children 10 to 12 years old was completed by the parent (proxy report), whereas the FAQLQ form for adolescents was completed by the adolescent (self-report). Scores were compared using the Wilcoxon rank sum test. Independent median regressions were used to test association between potential risk factors and QoL outcomes. Results In our cohort, the median FAQLQ score was significantly higher (reflecting lower QoL) in adolescents compared with children (4.7 vs 3.5, P = .007). The median social and dietary limitations score (5.2 vs 4, P = .002) and the median emotional impact score (3.8 vs 3.1, P = .02) were also higher in adolescents. Limitations in family activities because of food allergy had a negative effect on QoL. Conclusion Food allergic adolescents are affected more than younger children (based on parental report) in terms of QoL, with a direct reflection on all areas of their daily life (emotional, dietary, and social). In addition, limitations in family activities because of the child′s food allergy significantly worsen the QoL and well being of all family members.

Background Tolerance development is an important clinical outcome for infants with cow's milk allergy. Objective This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid–based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. Methods Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set. Results At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036). Conclusions After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Disparities in health outcomes in underrepresented racial and ethnic minority groups are evident in allergic/immunologic diseases, and has been most completely described in asthma. The last two decades have not led to any substantive improvement in these disparities, with underrepresented minorities (URMs) receiving worse care in several quality measures. Increasing physician workforce diversity is one strategy to improve access to care and address the health disparity problem because URM physicians more often choose to both work in clinical settings and pursue research that benefits underserved communities. The pipeline for practicing allergists and immunologists should be facilitated to ensure there are enough providers for patients in the growing URM populations. Having clear data measures of the active workforce and trainees in our specialty is required. Outreach to historically minority institutions to raise awareness of the field of allergy/immunology, forging partnerships with student medical associations and increasing national incentives to fund research or loan forgiveness for those who undertake careers in AI from URM backgrounds are also critical. Supporting the retention and advancement of URM medical school faculty will increase the visibility of the specialty to potential trainees. Intentional strategies will be important to ensure our specialty can meet the demand of a diverse patient population.

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and recurrent bacterial skin infections.

The prevalence of peanut allergies has escalated over the last 20 years, yet there are no FDA approved treatments for peanut allergies. In this study we evaluated the potential of microneedles to deliver peanut protein extract (PE) into skin and assessed if the ensuing immune responses could desensitize mice that were sensitized to peanuts. Peanut sensitized mice were either treated through cutaneous immunotherapy using PE-coated microneedles or not treated, and then orally challenged with PE. After oral challenge, the clinical symptoms of peanut-induced anaphylaxis were significantly lower in the microneedle treated mice as compared to untreated mice, and this was accompanied by down-regulation of systemic anaphylaxis mediators such as histamine and mast cell protease-1 (MCPT-1) in the microneedles treated group. Overall, there was an up-regulation of Th1 cytokines (IL-2 and IFN-γ) as compared to Th2 cytokines (IL-4 and IL-5) in splenocyte culture supernatants of the microneedle treated group as compared to untreated group, suggesting that microneedles promoted immune modulation towards the Th1 pathway. Furthermore, mice treated with PE-coated microneedles were observed to retain integrity of their small intestine villi and had reduced eosinophilic infiltration as compared to the untreated but peanut sensitized mice, which further confirmed the desensitization capability of peanut cutaneous immunotherapy using coated microneedles. Thus, our current study represents a novel minimally invasive microneedle based cutaneous immunotherapy, which may provide a novel route of desensitization for the treatment of peanut allergies.

Background Food protein–induced enterocolitis syndrome (FPIES) is an infrequent non–IgE-mediated gastrointestinal allergic disorder that occurs mostly in infants and young children. FPIES food triggers vary among different geographic locations, and the condition is still underdiagnosed and underrecognized. Objective To identify the triggers, characteristics, and management of FPIES in a pediatric US population of 74 children presenting to a tertiary center during a 3-year period. Methods We performed a retrospective electronic record review of all pediatric patients with a diagnosis of FPIES who presented to Texas Children's Hospital emergency centers and clinics. Results Most of our patients were white, and 65% had a positive family history of atopy. The median age at the first FPIES episode was 5 months (interquartile range, 4-6 months), and the median age at diagnosis was 11 months (interquartile range, 7-16 months). Grains (88%), cow's milk (49%), and vegetables (43%) were the most common food triggers in our cohort. Of the fruits, banana (24%) and avocado (16%) were predominantly reported. More than half of our patients experienced FPIES to multiple food triggers. Conclusion In our cohort, rice (53%) was the most common individual food trigger, surpassing cow's milk and soybean, previously reported as the most prevalent FPIES triggers in the United States. Banana (24%) and avocado (16%) rates were also much higher than in other studied populations, likely a reflection of different dietary and weaning habits in our area. Time from disease presentation to diagnosis was delayed, potentially because of difficulties in disease recognition. We noted a significant percentage of multiple-food FPIES in contrast to other populations.

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:2 pages:659-670 ispartof: location:United States status: published

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer’s disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. Participants: Healthy subjects without cognitive deficits =65years, and those with Alzheimer’s Disease were assessed. Intervention: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. Measurements: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. Results: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p

IMPORTANCE: Equitable representation of participants who are members of racial and ethnic minority groups in clinical trials enhances inclusivity in the scientific process and generalizability of results. OBJECTIVE: To assess participant race and ethnicity in pediatric clinical trials published from 2011 to 2020. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study examined articles reporting pediatric clinical trials conducted in the US published in 5 leading general pediatric and 5 leading general medical journals from January 1, 2011, to December 31, 2020. MAIN OUTCOMES AND MEASURES: Reporting of participant race and ethnicity and comparison of enrolled participants vs US census populations of pediatric racial and ethnic groups in published clinical trials. RESULTS: The study included 612 articles reporting pediatric clinical trials during the study period, with 565 618 total participants (median per trial, 200 participants [IQR, 90-571 participants]). Of the 612 articles, 486 (79.4%) reported participant race and 338 (55.2%) reported participant ethnicity. From 2011 to 2020, relative rates of reporting of participant race increased by 7.9% per year (95% CI, 0.2%-16.3% per year) and reporting of ethnicity increased by 11.4% per year (95% CI, 4.8%-18.4% per year). Among articles reporting race and ethnicity, the method of assignment was not reported in 261 of 511 articles (51.1%) and 207 of 359 articles (57.7%), respectively. Black/African American children were enrolled proportionally more than the US population of Black/African American children (odds ratio [OR], 1.88; 95% CI, 1.87-1.89). Hispanic/Latino children were enrolled commensurately with the US population of Hispanic/Latino children (OR, 1.02; 95% CI, 1.01-1.03). American Indian/Alaska Native (OR, 0.82; 95% CI, 0.79-0.85), Asian (OR, 0.56; 95% CI, 0.55-0.57), and Native Hawaiian/Pacific Islander (OR, 0.66; 95% CI, 0.61-0.72) children were enrolled significantly less compared with the respective US populations of these groups. White children were enrolled less than expected (OR, 0.84; 95% CI, 0.84-0.85) but represented 188 156 (46.0%) of participants in trials reporting race or ethnicity. CONCLUSIONS AND RELEVANCE: This cross-sectional study revealed that the proportion of published pediatric clinical trials that reported participant race and ethnicity increased from 2011 to 2020, but participant race and ethnicity were still underreported. Disparities existed in pediatric clinical trial enrollment of American Indian/Alaska Native, Asian, and Native Hawaiian/Pacific Islander children. The greater representation of Black/African American children compared with the US population suggests inclusive research practices that could be extended to other historically disenfranchised racial and ethnic groups.

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5–12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. The distribution frequency of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) from peripheral blood samples were measured in vitro. A general linear mixed model was used, and included fixed effects for cohort (responder, non-responder, or healthy control), time (0-, 6-, 12-, 18-, and 24-weeks), and the cohort-time interaction term. P-values were adjusted for multiple hypothesis testing using Tukey’s method. We observed that POIT responders had reduced TNFa producing myeloid dendritic cells (mDCs) compared to non-responders. Additionally, non-responders had increased OX40L expressing mDCs at 18-weeks compared to responders. In conclusion, our findings suggest that a reduced pro-inflammatory phenotype in DCs could potentially serve as a predictor of early outcome and success of POIT desensitization.

The maximum tolerated dose of peanut protein following peanut oral immunotherapy (POIT) is unknown because most research studies have not examined very high thresholds.To define the maximum dose tolerated by patients on POIT and severity of allergic reactions after a 1-month period of treatment discontinuation.In a phase 2 3-year POIT open-label study, we enrolled participants age 5 to 13 years with a 1-year build-up period followed by a 2-year daily maintenance dose of 3900 mg with assessment of the maximum tolerated dose using double-blind placebo-controlled food challenges (DBPCFCs) of 26,225 mg cumulative dose of peanut protein. The DBPCFC was performed at baseline, after 12-month build-up, at 2 year of maintenance, and after a 1-month period of treatment discontinuation. Biomarkers were assessed every 6 weeks for the first 6 months of therapy. A general linear mixed model was used for analysis.The mean maximum cumulative tolerated dose after 12 months increased by 12,063 mg (P.001) (n = 12), slightly decreased during maintenance (n = 11), and significantly decreased by 7593 mg after avoidance for 1 month (P = .03) (n = 6). Biomarker analysis revealed decreases in cytokine expression within the first 6 weeks of initiation of POIT and decreased peanut-IgGThe evaluation of POIT and sustained unresponsiveness by maximum tolerated dose by DBPCFCs in this small phase 2 trial showed that desensitization is diminished, with 100% loss of tolerated dose after 1 month of avoidance following 3 years of treatment.

Miniplate osteosynthesis has revolutionised the treatment of open reduction and internal fixation in craniomaxillofacial procedures. However, when complications arise necessitating the removal of previously placed miniplates, bony overgrowth may be present and must be eliminated before removal of the hardware is possible. Osteogenesis over the screws prevents proper engagement of the screwdriver with the screw drives. If bone remains embedded in the screw drive during attempted removal of the screw, the contact interference increases the risk of the screwdriver slipping and the screw drive being stripped. There remains a lack of adequate techniques to clear bony overgrowth from miniplates and screws to allow for easy removal, as conventional methods are ineffective, time-consuming, and may damage the screw drives. Herein, we describe a new laser-assisted miniplate removal technique to eliminate bone that has grown over miniplates and screws before the miniplate is removed. This technique is efficient, safe, and simple and, compared with conventional methods, may decrease the complications associated with the removal of miniplates and screws.

Background Intestinal microbes have been shown to influence predisposition to atopic disease, including food allergy. The intestinal microbiome of food-allergic children may differ in significant ways from genetically similar non-allergic children and age-matched controls. The aim was to characterize fecal microbiomes to identify taxa that may influence the expression of food allergy. Methods Stool samples were collected from children with IgE-mediated food allergies, siblings without food allergy, and non-allergic controls. Stool microbiome characterization was performed via next-generation sequencing (Illumina) of the V1V3 and V4 variable regions of the 16S rRNA gene. Bacterial diversity, evenness, richness, and relative abundance of the operational taxonomic units (OTUs) were evaluated using QIIME. ANOVA and Welch's t test were utilized to compare groups. Results Sixty-eight children were included: food-allergic (n = 22), non-food-allergic siblings (n = 25), and controls (n = 21). When comparing fecal microbial communities across groups, differences were noted in Rikenellaceae (P = .035), Actinomycetaceae (P = .043), and Pasteurellaceae (P = .018), and nine other distinct OTUs. Food-allergic subjects had enrichment for specific microbes within the Clostridia class and Firmicutes phylum (Oscillobacter valericigenes, Lachnoclostridium bolteae, Faecalibacterium sp.) compared to siblings and controls. Identification of Clostridium sp. OTUs revealed differences in specific Clostridia drive the separation of the allergic from the siblings and controls. Alistipes sp. were enriched in non-allergic siblings. Conclusions Comparisons in the fecal microbiome of food-allergic children, siblings, and healthy children point to key differences in microbiome signatures, suggesting the role of both genetic and environmental contributors in the manifestation of food-allergic disease.

A Henderson, A Magier, JT Schwartz. J Pediatr Gastroenterol Nutr. 2020;70(4):482–488 Since a minimally invasive biomarker for disease is desperately needed in eosinophilic esophagitis (EoE), the purpose of this study was to evaluate if peripheral circulating eosinophil progenitors (EoP) could be used as a biomarker for active disease in pediatric EoE patients. Thirty-four total samples from 31 individuals were included in the final analysis. The study participants included pediatric patients, ages 4 to 17 years, including 18 individuals with inactive EoE and 16 with active EoE at the time of endoscopy. Most patients were white boys (70% boys; 97% white), which is consistent with the known disease demographics. In this prospective observational study, peripheral blood …

Modern immunologic studies demand increasing complexity because of a need to improve our understanding of the relationship between a cell's phenotype and its function. Regulatory T cells (Tregs) have been defined by a narrow set of phenotypic markers, however their actual functional capacity has not been determined at the single-cell level. Although the lymphocyte activation gene 3 (LAG-3; CD223) is a key marker for the identification of exhausted T cells, it may be useful also in resolving Treg subpopulations by indicating distinct functional breadths. Here we define the experimental conditions necessary for the optimal detection by flow cytometry of LAG-3 expression on activated Tregs. We stimulated human PBMCs with either PMA/ionomycin or Staphylococcal Enterotoxin B (SEB) and analyzed CD4+CD25+FoxP3+ Tregs for LAG-3 expression in concert with other Treg phenotypic markers. We prescribe a 24-hour stimulation period for the optimal detection of LAG-3 on Tregs. Furthermore, we determine LAG-3 protein expression on Tregs is compromised when the cells are treated with brefeldin A (BFA) and monensin. Therefore, the simultaneous assessment of Treg phenotype and function is complicated by the use of protein transport inhibitors.