Food allergy as a biological food quality control system.

Food is simultaneously a source of essential nutrients and a potential source of lethal toxins and pathogens. Consequently, multiple sensory mechanisms evolved to monitor the quality of food based on the presence and relative abundance of beneficial and harmful food substances. These include the olfactory, gustatory, and gut chemosensory systems. Here we argue that, in addition to these systems, allergic immunity plays a role in food quality control by mounting allergic defenses against food antigens associated with noxious substances. Exaggeration of these defenses can result in pathological food allergy.

Local immune response to food antigens drives meal-induced abdominal pain.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Utility of food allergy thresholds.

Food allergy is a prevalent disease worldwide that is a significant quality-of-life burden, and accidental exposures to food allergens may elicit severe, life-threatening reactions such as anaphylaxis. The threshold level, or the dose that triggers an allergic reaction determined by oral food challenges, varies considerably among individuals suffering from food allergies. Moreover, IgE concentration, diversity, or function can only partially explain this variation in threshold; pathogenic effector TH2 cells have also been found to contribute to the eliciting dose. Though very sensitive to cofactors such as physical activity/stress, the threshold is a stable and reproducible feature of an individual's allergy over periods of many months, made clear in the past several years from treatment studies in which repeated threshold determination has been used as a treatment outcome; however, there also seem to be age-related changes at a population level. More routine determination of food allergy thresholds may help patients stratify risk to improve the management of their food allergy. Precautionary allergen labeling, such as "may contain" labels, often causes confusion since they are inconsistent and regularly contain little to trace allergen residues; thus, food products with such labeling may be unnecessarily avoided. Population-based eliciting dose levels have been determined in the literature; patients at lower risk with higher thresholds may be more confident with introducing foods with precautionary allergen labels. Understanding a patient's threshold level could aid in shared decision-making to determine the most suitable treatment options for patients, including the starting dose for oral immunotherapy and/or the use of biologics.

Esophageal food bolus impaction in pediatric age.

OBJECTIVES: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children. METHODS: We have prospectively enrolled all children admitted for a first episode of EFI between March 2018 and March 2023. A fluoroscopic contrast study was performed in all patients to confirm the boluses and assess their position. Boluses were extracted by esophagogastroduodenoscopies, and esophageal biopsies were routinely obtained for histologic evaluation. RESULTS: Over the study period, 41 children were admitted for a first episode of food impaction. Drooling was the most commonly reported symptom. Half children experiencing a first episode of food bolus were diagnosed with EoE (20/41, 48.8%). Almost a fourth of the episodes subtended a different condition, such as esophageal anastomotic, peptic or congenital strictures, stricturing caustic esophagitis, esophageal duplication, and achalasia. In the last fourth of patients the cause of EFI was not identified and thus probably related to quick eating and inadequate chewing of food. DISCUSSION: Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI to provide a complete diagnostic evaluation.

Eosinophilic oesophagitis: a common cause of food bolus obstruction.

BACKGROUND: Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence. AIMS: To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy. METHODS: Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented. RESULTS: One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7-year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow-up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE. CONCLUSION: EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment.

Gastrointestinal adverse reaction to food (GARF) and endoscopic confocal laser endomicroscopy (eCLE).

BACKGROUND AND STUDY AIMS: Gastrointestinal adverse reaction to food (GARF) is reported frequently in the general population and even more in patients with disorders of the gut brain axis. However, there is a significant difference between self-reported and objective proven GARF. The aim of the study was to characterize a mucosal correlate of GARF by endoscopic confocal laser endomicroscopy (eCLE) with duodenal food challenge (DFC). PATIENTS AND METHODS: In an observational and proof of concept study we evaluated 71 patients with disorders of the gut brain axis without (group I, n=19) and with (group II, n=52) GARF by eCLE and DFC. Spontaneous and food induced transfer of fluorescein into duodenal lumen was detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. RESULTS: According to Rom IV, the patients (group I/II) could be classified as irritable bowel syndrome (IBS) 32%/31%, functional abdominal pain without changes in bowel movement 47 %/48 %, functional abdominal bloating/distension 0 %/10 %, functional diarrhea 5 %/ 2 %, and unspecified functional bowel disorder 16 %/10 %, respectively. 21 %/27 % of the patients responded with a fluorescein leakage into the duodenal lumen before and 74 %/69 % following to DFC. Frequency rank order of food components that induced a response were soy (55.5 %/60 %), wheat (60 %/45.5 %), egg (35.7 %/8.3), milk (30 %/18.2 %) and yeast (10 %/6.6 %), respectively. Histology of duodenal biopsies, number, form and distribution of intraepithelial lymphocytes and mucosal mast cells as well as mast cell function were normal. Overall, 14 %/79 % reported main symptom benefit following a food exclusion therapy according to eCLE and DFC that was significant different between the groups. CONCLUSION: The results of our study indicate that eCLE with DFC is a technique to clinically evaluate patients with disorders of the gut brain axis and GARF resulting in a high proportion of patients reporting symptom benefit upon food exclusion dietary advice focussed on the results of eCLE.

Treatment for food allergy: Current status and unmet needs.

The treatment of food allergy has traditionally relied on avoidance of the offending food(s) and use of emergency medications in the event of accidental exposures. However, this long-standing paradigm is beginning to shift, as a variety of treatment approaches have been and are being developed. This report provides an overview of the past, present, and future landscape of interventional clinical trials for the treatment of food allergy. It focuses on specific issues related to participant characteristics, protocol design, and study end points in the key clinical trials in the literature and examine how differences between studies may impact the clinical significance of the study results. Recommendations are provided for the optimization of future trial designs and focus on specific unmet needs in this rapidly evolving field.

Bulk T-cell receptor sequencing confirms clonality in pediatric eosinophilic esophagitis and identifies a food-specific repertoire.

BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.

Fatal and near-fatal anaphylaxis: The Allergy-Vigilance® Network data (2002-2020).

BACKGROUND: Having a better understanding of the risk factors of severe anaphylaxis is a crucial challenge for physicians. METHODS: To retrospectively analyse fatal/near-fatal anaphylaxis cases recorded by the Allergy-Vigilance® Network (2002-2020) and evaluate the characteristics associated with survival, age and allergens. RESULTS: Among the 3510 anaphylaxis cases documented in the network, 70 (2%) patients (males: 57%; mean age: 35.4 y) presented grade 4 (Ring-Messmer) anaphylaxis and 25 died (19 food-related); 33% had a history of asthma. The main allergens were food (60%; peanut, 20%; milks, 11%) involved in 25/26 cases in children and in 17/44 (39%) cases in adults. Non-food anaphylaxis was related to drugs/latex (24%; neuromuscular blocking agents, 10%; betalactamins, 6%), Hymenoptera (16%). Three food-related cases (one death) occurred during oral food challenge in children. Patients with a food allergy were younger (22.2 years vs. 55 years, p < .001), had more likely a history of asthma (50% vs. 7%; p < .001), a pre-existing allergy (62% vs. 18%; p < .001) compared with other allergies. A cofactor was identified in 35 cases (50%) but predominantly in adults as opposed to children (64% vs. 27%; p = .01). The patients who died were younger (25.6 vs. 40.8 years; p = .01) than the survivors and mostly presented bronchospasm (56% vs. 29%; p = .05). Gaps in the prevention and management of anaphylaxis were noted in 15 cases (21%). CONCLUSIONS: Severe food anaphylaxis has specific features compared with other causes such as young age, asthma history and exercise. Food is also involved in severe anaphylaxis in adults that should not be underestimated.

Cofactors in food anaphylaxis in adults.

Around 25% to 50% of food-induced allergic reactions in adults cause anaphylaxis, and epidemiologic evidence suggests that food is the most common cause of anaphylaxis. Reaction severity is unpredictable, and patients will often experience reactions of variable severity, even to an identical exposure (both dose and allergen). A common explanation for this phenomenon has been the impact of "cofactors"-factors that might contribute to reaction severity independent of the allergen exposure. Cofactors can influence reaction severity in 2 ways: either by reducing the reaction threshold (ie, the dose needed to trigger any symptoms) so that patients have no symptoms in the absence of the cofactor and only react with the cofactor present, or by increasing reaction severity such that individuals have only mild symptoms in the absence of the cofactor, but a more severe reaction when the cofactor is present. Indeed, the same patient may have reactions with different cofactors or even need more than one cofactor to develop a severe reaction. Cofactors reportedly play a role in approximately 30% of anaphylaxis reactions in adults. Exercise, nonsteroidal, anti-inflammatory drugs, alcohol, and sleep deprivation are the most frequent cofactors reported. Routine evaluation of the possible involvement of cofactors is essential in managing patients with food anaphylaxis: in patients with a suggestive history but a negative oral food challenge, cofactors should be taken into account to provide appropriate advice to reduce the risk of future anaphylaxis.

Comparable Efficacy for Push Versus Pull Technique in Esophageal Food Impaction: Systematic Review with Meta-Analysis.

BACKGROUND: Esophageal food impaction (EFI) is a common GI emergency. Push and pull methods are used currently for EFI retrieval. We aim to review current available literature to compare success rates and evaluate adverse event rates of the two techniques. METHODS: A comprehensive literature search was performed using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, KCI-Korean Journal Index, SciELO and Global Index Medicus. Odds ratio (OR) with 95% confidence interval (CI) was calculated when comparing the dichotomous variables. We aimed to evaluate technical success and adverse events for EFI comparing push and pull technique on single arm and comparator analysis. RESULTS: The search strategy yielded a total of 126 articles. 18 studies with 3528 participants were included. The technical success rate was 97.5% (CI 96.6-99.2%) in the push and 88.4% (CI 72.8-98.7%) in the pull technique with no statistical difference on comparator analysis. Overall rate of adverse events was 4.03% (CI 0.9-5.0%) in the push technique and 2.22% (CI 0-2.9%) in the pull technique with no statistical difference on comparator analysis (OR 95% CI 0.464-2.782, p = 0.78, I2 = 31.54%). There was no statistical difference between rate of lacerations and perforations either between the two techniques. CONCLUSION: Both techniques have acceptable clinical outcomes which appear within standard of care. Operator experience and individual clinical scenarios should guide decision-making regarding technique selection.

Differences in child and adolescent exposure to unhealthy food and beverage advertising on television in a self-regulatory environment.

BACKGROUND: Food and beverage promotion is a contributor to children's dietary behaviours, and ultimately, downstream health consequences. Broadcast television remains an important source of such advertising. The objective of this study was to examine and compare children and adolescent's exposure to food advertising on television in Canada over an entire year in a self-regulatory environment. METHODS: Television advertising data for 57 selected food and beverage categories were licensed from Numerator for 36 stations in Toronto, for 2019. The estimated average number of advertisements viewed by children aged 2-11 and adolescents aged 12-17 was determined overall, by food category, and by marketing technique. The healthfulness of advertisements was also assessed using Health Canada's Nutrient Profile Model. RESULTS: Overall in 2019, children viewed 2234.4 food ads/person/yr while adolescents viewed 1631.7 ads, exposure for both groups stemmed primarily from stations with general appeal, and both age groups were exposed to a range of powerful marketing techniques. Exposure to advertising for restaurants, snacks, breakfast food and candy and chocolate was high among both age groups and the healthfulness of most advertised products was considered poor. Adolescents were exposed to 36.4% more food products classified as unhealthy, had higher exposure to all marketing techniques examined, and were exposed to substantially more child-related marketing techniques compared to children. CONCLUSION: Children and adolescents were heavily exposed to food advertisements on television in 2019. Despite current self-regulatory policies, children's exposure to unhealthy food and beverages remains high. Differences in exposure to food advertisements by food category and healthfulness may suggest that adolescents are being disproportionately targeted by food companies as a result of self-regulatory marketing restrictions.

Risk factors for severe reactions in food allergy: Rapid evidence review with meta-analysis.

This rapid review summarizes the most up to date evidence about the risk factors for severe food-induced allergic reactions. We searched three bibliographic databases for studies published between January 2010 and August 2021. We included 88 studies and synthesized the evidence narratively, undertaking meta-analysis where appropriate. Significant uncertainties remain with respect to the prediction of severe reactions, both anaphylaxis and/or severe anaphylaxis refractory to treatment. Prior anaphylaxis, an asthma diagnosis, IgE sensitization or basophil activation tests are not good predictors. Some molecular allergology markers may be helpful. Hospital presentations for anaphylaxis are highest in young children, yet this age group appears at lower risk of severe outcomes. Risk of severe outcomes is greatest in adolescence and young adulthood, but the contribution of risk taking behaviour in contributing to severe outcomes is unclear. Evidence for an impact of cofactors on severity is lacking, although food-dependent exercise-induced anaphylaxis may be an exception. Some medications such as beta-blockers or ACE inhibitors may increase severity, but appear less important than age as a factor in life-threatening reactions. The relationship between dose of exposure and severity is unclear. Delays in symptom recognition and anaphylaxis treatment have been associated with more severe outcomes. An absence of prior anaphylaxis does not exclude its future risk.

Fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus, and hypertension in adults: a meta-analysis of observational studies.

Recent studies have reported conflicting associations of fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus (T2DM) and hypertension, and a meta-analysis is not available. We aimed to explore the association between fried-food consumption and risk of overweight/obesity, T2DM and hypertension in adults through a meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published up to 17 June 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. In comparing the highest to lowest fried-food intake, the pooled RRs (95% CIs) were 1.16 (1.07-1.25; I2 = 71.0%, Pheterogeneity < 0.001) for overweight/obesity (cohort: 1.19 [0.97-1.47], n = 2; cross-sectional: 1.14 [1.03-1.27], n = 9), 1.07 (0.90-1.27; 84.7%) for T2DM (cohort: 1.01 [0.89-1.15], n = 9; case-control: 2.33 [1.80-3.01], n = 1), and 1.20 (1.05-1.38; I2=91.8%) for hypertension (cohort: 1.06 [0.98-1.15], n = 8; cross-sectional: 2.16 [0.59-7.87], n = 3). Our meta-analysis indicates fried-food consumption is associated with increased risk of overweight/obesity and hypertension but not T2DM in adults, but the findings should be interpreted with caution due to high heterogeneity and unstable subgroup analyses of this meta-analysis. More studies are warranted to investigate the total fried-food consumption and these health outcomes.

The dilemma of open or double-blind food challenges in diagnosing food allergy in children: Design of the ALDORADO trial.

BACKGROUND: It is of major importance to diagnose food allergy accurately. Current guidelines support the use of oral food challenges to do so. The double-blind placebo-controlled food challenge (DBPCFC) has been regarded as the 'gold standard' for decades. However, DBPCFCs are costly, and time- and resource-intensive procedures. Structural implementation of less demanding open food challenges will only find support if research demonstrates that their outcome is comparable to DBPCFC, yet this has been proven difficult to investigate. METHODS: We performed a literature review to investigate the diagnostic accuracy of oral food challenges and interviewed 19 parents of children with proven or suspected food allergy about the design of a trial to study this. RESULTS: An overview of the dilemma of diagnosing food allergy using oral food challenges, and the methodological issues and parents' opinions to study this. No comparative studies have been performed using the latest guidelines on oral food challenges. CONCLUSIONS: There is an urgent need to investigate the diagnostic accuracy of different oral food challenge protocols. We present the rationale and design of the ALDORADO trial (ALlergy Diagnosed by Open oR DOuble-blind food challenge) that has been set up to investigate whether the outcome of the open food challenge is comparable to DBPCFC.

Using data from food challenges to inform management of consumers with food allergy: A systematic review with individual participant data meta-analysis.

BACKGROUND: Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown. OBJECTIVE: Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge. METHODS: We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists. RESULTS: A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis. CONCLUSION: Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.

Altering product placement to create a healthier layout in supermarkets: Outcomes on store sales, customer purchasing, and diet in a prospective matched controlled cluster study.

BACKGROUND: Previous product placement trials in supermarkets are limited in scope and outcome data collected. This study assessed the effects on store-level sales, household-level purchasing, and dietary behaviours of a healthier supermarket layout. METHODS AND FINDINGS: This is a prospective matched controlled cluster trial with 2 intervention components: (i) new fresh fruit and vegetable sections near store entrances (replacing smaller displays at the back) and frozen vegetables repositioned to the entrance aisle, plus (ii) the removal of confectionery from checkouts and aisle ends opposite. In this pilot study, the intervention was implemented for 6 months in 3 discount supermarkets in England. Three control stores were matched on store sales and customer profiles and neighbourhood deprivation. Women customers aged 18 to 45 years, with loyalty cards, were assigned to the intervention (n = 62) or control group (n = 88) of their primary store. The trial registration number is NCT03518151. Interrupted time series analysis showed that increases in store-level sales of fruits and vegetables were greater in intervention stores than predicted at 3 (1.71 standard deviations (SDs) (95% CI 0.45, 2.96), P = 0.01) and 6 months follow-up (2.42 SDs (0.22, 4.62), P = 0.03), equivalent to approximately 6,170 and approximately 9,820 extra portions per store, per week, respectively. The proportion of purchasing fruits and vegetables per week rose among intervention participants at 3 and 6 months compared to control participants (0.2% versus -3.0%, P = 0.22; 1.7% versus -3.5%, P = 0.05, respectively). Store sales of confectionery were lower in intervention stores than predicted at 3 (-1.05 SDs (-1.98, -0.12), P = 0.03) and 6 months (-1.37 SDs (-2.95, 0.22), P = 0.09), equivalent to approximately 1,359 and approximately 1,575 fewer portions per store, per week, respectively; no differences were observed for confectionery purchasing. Changes in dietary variables were predominantly in the expected direction for health benefit. Intervention implementation was not within control of the research team, and stores could not be randomised. It is a pilot study, and, therefore, not powered to detect an effect. CONCLUSIONS: Healthier supermarket layouts can improve the nutrition profile of store sales and likely improve household purchasing and dietary quality. Placing fruits and vegetables near store entrances should be considered alongside policies to limit prominent placement of unhealthy foods. TRIAL REGISTRATION: ClinicalTrials.gov NCT03518151 (pre-results).

Adolescent animal product intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study.

BACKGROUND: Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence. METHODS: We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12-13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,349), advanced (n = 2,297) and fatal (n = 804) PCa. RESULTS: Suggestive inverse trends were observed for adolescent unprocessed beef intake with risks of total, advanced and fatal PCa (multivariable-adjusted P-trends = 0.01, 0.02 and 0.04, respectively). No consistent patterns of association were observed for other animal products by PCa outcome. CONCLUSION: We found evidence to suggest that adolescent unprocessed beef intake, or possibly a correlate of beef intake, such as early-life socioeconomic status, may be associated with reduced risk and mortality from PCa. Additional studies with further early-life exposure information are warranted to better understand this association.

Comparison of Cap-Assisted vs Conventional Endoscopic Technique for Management of Food Bolus Impaction in the Esophagus: Results of a Multicenter Randomized Controlled Trial.

INTRODUCTION: "Push" or "pull" techniques with the use of snares, forceps, baskets, and grasping devices are conventionally used to manage esophageal food bolus impaction (FBI). A novel cap-assisted technique has recently been advocated to reduce time taken for food bolus (FB) removal. This study aimed to compare the effectiveness of the cap-assisted technique against conventional methods of esophageal FB removal in a randomized controlled trial. METHODS: Consecutive patients with esophageal FBI requiring endoscopic removal, from 3 Australian tertiary hospitals between 2017 and 2019, were randomized to either the cap-assisted technique or the conventional technique. Primary outcomes were technical success and FB retrieval time. Secondary outcomes were technical success rate, en bloc removal rate, procedure-related complication, length of hospital stay, and cost of consumables. RESULTS: Over 24 months, 342 patients with esophageal FBI were randomized to a cap-assisted (n = 171) or conventional (n = 171) technique. Compared with the conventional approach, the cap-assisted technique was associated with (i) shorter FB retrieval time (4.5 ± 0.5 minutes vs 21.7 ± 0.9 minutes, P < 0.001), (ii) shorter total procedure time (23.0 ± 0.6 minutes vs 47.0 ± 1.3 minutes, P < 0.0001), (iii) higher technical success rate (170/171 vs 160/171, P < 0.001), (iv) higher rate of en bloc removal (159/171 vs 48/171, P < 0.001), and (v) lower rate of procedure-related mucosal tear and bleeding (0/171 vs 13/171, P < 0.001). There were no major adverse events or deaths within 30 days in either group. The total cost of consumables was higher in the conventional group (A$19,644.90 vs A$6,239.90). DISCUSSION: This multicenter randomized controlled trial confirmed that the cap-assisted technique is more effective and less costly than the conventional approach and should be first-line treatment for esophageal FBI.

Food-induced immediate response of the esophagus-A newly identified syndrome in patients with eosinophilic esophagitis.

BACKGROUND: Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as "food-induced immediate response of the esophagus" (FIRE), observed in EoE patients. METHODS: Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. RESULTS: Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food-induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). CONCLUSIONS: Food-induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.