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Water disinfection is usually evaluated using mandatory methods based on cell culturability. However, such methods do not consider the potential of cells to recover, which should also be kept as low as possible. In this paper, we hypothesized that a successful disinfection is achieved only when the applied chlorine leads to both intracellular nucleic acid damage and strong alterations of the DNA repair machinery. Monitoring the SOS system responsiveness with a umuC'-'lacZ reporter fusion, we found that the expression of this important cellular machinery was altered after the beginning of membrane permeabilization but prior to the total decline of both the cell culturability and the nucleic acid integrity as revealed by Sybr-II staining. Rapid measurement of such nucleic acid alterations by fluorochrome-based staining could be used as an alternative method for assessing the effectiveness of disinfection with chlorine. [ABSTRACT FROM AUTHOR]

BACKGROUND Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleu-kin-13 signaling, which have key roles in eosinophilic esophagitis. METHODS. We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing. The two primary end points at week 24 were histologic remission (<6 eosinophils per high-power field) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score (range, 0 to 84, with higher values indicating more frequent or more severe dysphagia). RESULTS In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P<0.001). In Part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [PcO.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI, 43 to 69 [not significant per hierarchical testing]). The mean (±SD) DSQ scores at baseline were 33.6±12.41 in Part A and 36.7±11.22 in Part B; the scores improved with weekly dupilumab as compared with placebo, with differences of -12.32 (95% CI, -19.11 to -5.54) in Part A and -9.92 (95% CI, -14.81 to -5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, -0.51; 95% CI, -5.42 to 4.41). Serious adverse events occurred in 9 patients during the Part A or B treatment period (in 7 who received weekly dupilumab, 1 who received dupilumab every 2 weeks, and 1 who received placebo) and in 1 patient in the Part A-C group during the Part C treatment period who received placebo in Part A and weekly dupilumab in Part C). CONCLUSIONS Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03633617.). [ABSTRACT FROM AUTHOR]

Background: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear., Objective: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents., Methods: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models., Results: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains., Conclusions: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children., Competing Interests: Disclosure statement CEGIR (U54 AI117804) is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is funded through a collaboration between NIAID, the National Institute of Diabetes and Digestive and Kidney Diseases, and NCATS and funded in part by the Division of Intramural Research, NIAID. CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases, and Eosinophilic Family Coalition. As a member of the Rare Disease Clinical Research Network, CEGIR is supported by its Data Management and Coordinating Center (grant no. U2CTR002818). Funding support for the Data Management and Coordinating Center is provided by NCATS and the National Institute of Neurological Disorders and Stroke. G.S.H. is supported by a grant from the National Institutes of Health (NIH) (grant no. K23 DK131341). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosure of potential conflict of interest: M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nexstone One, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, AstraZeneca, Pfizer, GlaxoSmithKline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first 9 listed; receives royalties from Teva Pharmaceuticals (reslizumab), Mapi Research Trust (PEESSv2.0), and UpToDate; and is an inventor of patents owned by Cincinnati Children’s Hospital. J. M. Spergel is a consultant for ReadySetfood, Regeneron/Sanofi, and ARS Pharma; has grant support from Novartis, Regeneron/Sanofi, Bristol Myers Squibb, Food Allergy Research and Education (FARE), and NIH; receives royalties from UpToDate; and serves on the Data Safety and Monitoring Board for Alladapt and NIAID. M. H. Collins is a consultant for Allakos, Arena/Pfizer, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Robarts Clinical Trials, Inc/Alimentiv, Inc, and Shire/Takeda. S. S Aceves is a consultant and an educational speaker for Regeneron/Sanofi; has grant support from the NIH, Campaign Urging Research for Eosinophilic Diseases, Bristol Myers Squibb, and Implicit Biosciences; and is a coinventor of oral viscous budesonide patented by the University of California San Diego and licensed by Takeda. M. Pletneva is a consultant for Allakos. S. K. Gupta is a consultant and/or Data Safety and Monitoring Board member for Adare, Bristol Myers Squibb, QOL, Takeda, Medscape, PVI, ViaSkin, and UpToDate; and receives research support from Allakos, Ellodi, and AstraZeneca. J. B. Wechsler is a consultant for Bristol Myers Squibb, Ellodi, AstraZeneca, Allakos, and Regeneron/Sanofi; and receives research support from Regeneron. N. Gonsalves is a consultant for AstraZeneca, Allakos, Sanofi/Regeneron, AbbVie, Knopp, and Bristol Myers Squibb; is on the speaker bureau for Sanofi/Regeneron; and receives publication royalties from UpToDate. G. W. Falk is a consultant for Allakos, Bristol Myers Squibb/Celgene, Adare/Ellodi, Nexstone, Upstream Bio, and Sanofi/Regeneron; and receives research support from Allakos, Adare/Ellodi, Bristol Myers Squibb/Celgene, and Regeneron/Sanofi. I. Hirano has received research funding from Adare Pharmaceuticals/Ellodi Pharmaceuticals, Allakos, AstraZeneca, Meritage Pharma, Inc, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, and Shire/Takeda; and is a consultant for Adare Pharmaceuticals/Ellodi Pharmaceuticals, Allakos, Arena Pharmaceuticals, Aslan Pharmaceuticals, AstraZeneca, Calyx/Parexel, Celldex Therapeutics, Inc, Dermavant, EsoCap Biotech, Gossamer Bio, Eli Lilly, Nexstone, Meritage Pharma, Inc, Phathom Pharmaceuticals, Receptos/Celgene/Bristol Myers Squibb, Sanofi/Regeneron Pharmaceuticals, and Shire/Takeda. M. Chehade has received consultant fees from Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Allakos, Shire/Takeda, and Phathom; and has received research support from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, and Danone. C. M. Davis has received grant funding from DBV Technologies, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis. E. S. Dellon is a consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/Bristol Myers Squibb, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GlaxoSmithKline, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; has received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GlaxoSmithKline, Meritage, Miraca, Nutricia, Celgene/Receptos/Bristol Myers Squibb, Regeneron, Revolo, and Shire/Takeda; and has received an educational grant from Allakos, Aqilion, Holoclara, and Invea. G. T. Furuta is Chief Medical Officer for EnteroTrack; and receives research funding from Arena/Pfizer. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Purpose: Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization., Methods: Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft. Change in corneal sensitivity (measured in millimeters by the Cochet-Bonnet aesthesiometer), visual acuity, and corneal health., Results: Over a mean follow-up period of 31.3 months (range: 3 months-8 years), mean corneal sensitivity improved from 3.6 mm (range: 0-25 mm) to 25.3 mm (range: 0-57 mm). Visual acuity improved on average from 20/380 to 20/260. Twelve of 16 patients (75.0%) improved in at least 2 out of the 3 main outcome measures. Nine patients (56.3%) showed an improvement in visual acuity; 13 (81.3%) showed an improvement in average corneal sensitivity; and 11 (68.8%) showed an improvement in corneal health. There were no intraoperative or postoperative complications., Conclusions: Corneal neurotization is an emerging surgical treatment option for the management of neurotrophic keratopathy. With appropriate case selection, outcomes are favorable and complication rates are low, for a condition that is otherwise challenging to manage. Patients with severe neurotrophic keratopathy should be considered for this surgical treatment option., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: Health-related decision-making is a complex process given the variability of treatment options, conflicting treatment plans, time constraints and variable outcomes. This complexity may result in patients experiencing decisional regret following decision-making. Nonetheless, literature on decisional regret in the healthcare context indicates inconsistent characterization and operationalization of this concept., Aim(s): To conceptually define the phenomenon of decisional regret and synthesize the state of science on patients' experiences with decisional regret., Design: A concept analysis., Methods: Rodgers' evolutionary method guided the conceptualization of this review. An interdisciplinary literature search was conducted from 2003 until 2023 using five databases, PubMed, CINAHL, Embase, PsycINFO and Web of Science. The search informed how the concept manifested across health-related literature. We used PRISMA-ScR checklist to guide the reporting of this review., Results: Based on the analysis of 25 included articles, a conceptual definition of decisional regret was proposed. Three defining attributes underscored the negative cognitive-emotional nature of this concept, post-decisional experience relating to the decision-making process, treatment option and/or treatment outcome and an immediate or delayed occurrence. Antecedents preceding decisional regret comprised initial psychological or emotional status, sociodemographic determinants, impaired decision-making process, role regret, conflicting treatment plans and adverse treatment outcomes. Consequences of this concept included positive and negative outcomes influencing quality of life, health expectations, patient-provider relationship and healthcare experience appraisal. A conceptual model was developed to summarize the concept's characteristics., Conclusion: The current knowledge on decisional regret is expected to evolve with further exploration of this concept, particularly for the temporal dimension of regret experience. This review identified research, clinical and policy gaps informing our nursing recommendations for the concept's evolution., No Patient or Public Contribution: This concept analysis examines existing literature and does not require patient-related data collection. The methodological approach does not necessitate collaboration with the public., (© 2024 John Wiley & Sons Ltd.)

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium., Competing Interests: Disclosure statement Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Disease Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCATS, and in part by the Division of Intramural Research, NIAID/NIH. CEGIR is also supported by patient advocacy groups including American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by the NCATS and the National Institute of Neurological Disorders and Stroke (NINDS). B.L.W. was funded by NIH/NIAID (K23AI158813). E.M.A. was funded by the NIH (KL2TR002552, K12TR004410). S.S.A. was funded by NIH/NIDDK (R56AI092135). S.J.A. was funded by NIH/National Heart, Lung, and Blood Institute (NHLBI) (R01HL153170). D.A.H. was directly supported by the Hartwell Foundation, the Food Allergy Fund, and a faculty development award from the American Academy of Allergy, Asthma & Immunology. Allergy research in the Hill laboratory was supported by NIH/NHLBI (R01HL162715) and the Children’s Hospital of Philadelphia Research Institute. J.W.C. was supported by the NIH (K23DK129784). F.L.K. was funded by APFED HOPE Pilot Grant 2023 and NIH/NIAID K23AI171085. M.A.R. was funded by the NIH (K08AI148456). L.A.S. was supported by NIH/NIAID (R01AI168134). The contents are those of the authors and do not necessarily represent the official views or an endorsement by the NIH or other funders. None of the funding sources had a role in the design or conduct of the study. Disclosure of potential conflict of interest: B. L. Wright reports in-kind support from Regeneron in the form of study drug (dupilumab and placebo) for a clinical trial of milk oral immunotherapy. J. P. Abonia reports receipt of payment or honoraria for lectures from Takeda Global Research and Development; participation on a data safety monitoring board for OctaPharma USA; and receipt of grants or contracts from Cures Within Reach and Celgene. E. M. Abud is coinventor of patent WO/2018/160496 (microglia differentiation and use); serves as advisory board member and consulting agreements with StemPharm and Neucyte; and reports advisory board participation for Amgen and AstraZeneca. S. S. Aceves is coinventor of oral viscous budesonide, patented by the University of California, San Diego, and licensed by Takeda (oral budesonide suspension); has acted as speaker for Regeneron/Sanofi; and has received research funding from Bristol Myers Squibb. S. J. Ackerman is chief science officer and executive board member of EnteroTrack; has received patents on the Esophageal String Test (EST); has consulted for Areteia Pharmaceuticals; and has participated on the medical advisory panel of the American Partnership for Eosinophilic Disorders (APFED). M. Braskett reports acting as scientific advisor to Bryn Pharma; and receipt of royalties from UpToDate. J. W. Chang reports consulting for Regeneron/Sanofi, Takeda, and Bristol Myers Squibb. M. Chehade reports consulting for Regeneron/Sanofi, Adare/Ellodi, AstraZeneca, Bristol Myers Squibb, Allakos, Shire/Takeda, Phathom, and Recludix Pharma; and receipt of research funding from Regeneron, Allakos, AstraZeneca, Adare/Ellodi, Bristol Myers Squibb, Danone, and Shire/Takeda. G. M. Constantine reports speaker honoraria from PeerView CME. C. M. Davis reports research funding from NIH/NIAID, DBV, Regeneron, AstraZeneca, Takeda, and Allergenis; and educational funding from Genentech. E. S. Dellon reports research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; consulting for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; and receipt of educational grants from Allakos, Aqilion, Holoclara, and Invea. R. Durban reports consulting for Sanofi, AstraZeneca, Reckitt/Mead Johnson Nutrition, Abbott Nutrition, and Nutricia North America. D. A. Hill has received a patent related to the utilization of food-specific T-cell responses for the diagnosis and management of EoE. E. T. Jensen reports consulting fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. A. Kewalramani reports sitting on the Sanofi Mid-Atlantic Regional Respiratory Field medical advisory board. P. Khoury and A. D. Klion report royalties from UpToDate. F. L. Kuang reports research funding from AstraZeneca. E. C. McGowan reports funding from NIH/NIAID and American College of Gastroenterology; and consulting for Regeneron/Sanofi and Takeda. J. M. Spergel reports grant support from the NIH, Regeneron/Sanofi, and Novartis; and has consulted for Regeneron/Sanofi, Allakos, Readysetfood, Novartis, and Bristol Myers Squibb. A. M. Uchida reports consulting for Regeneron/Sanofi, Takeda, and AstraZeneca. J. B. Wechslerc reports consulting for Allakos, Ellodi, Regeneron/Sanofi/Genzyme, Bristol Myers Squibb, Invea Therapeutics, CellDex, and AstraZeneca; and clinical trial/research funding from Allakos and Regeneron/Sanofi. R. D. Pesek reports consulting for Regeneron. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively affect quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy., Objective: We performed a multisite, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE., Methods: Patients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary end point was symptom improvement by Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary end points were proportion experiencing histologic remission (<15 eosinophils per high-power field); change in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome (EoE diagnostic panel), and QoL scores; and predictors of remission., Results: Sixty-three patients were randomly assigned to 1FED (n = 38) and 4FED (n = 25). In 4FED versus 1FED, mean PEESS improved -25.0 versus -14.5 (P = .04), but remission rates (41% vs 44%; P = 1.00), histology scoring system (-0.25 vs -0.29; P = .77), endoscopic reference score (-1.10 vs -0.58; P = .47), and QoL scores were similar between groups. The EoE transcriptome normalized in those with histologic response to both diets. Baseline peak eosinophil count predicted remission (odds ratio, 0.975 [95% confidence interval, 0.953-0.999], P = .04; cutoff ≤42 eosinophils per high-power field). The 4FED withdrawal rate (32%) exceeded that of 1FED (11%) (P = .0496)., Conclusions: Although 4FED moderately improved symptoms compared with 1FED, the histologic, endoscopic, QoL, and transcriptomic outcomes were similar in both groups. 1FED is a reasonable first-choice therapy for pediatric EoE, given its effects, tolerability, and relative simplicity., Competing Interests: Disclosure statement Funded through a Patient-Centered Outcomes Research Institute (PCORI) award (CER-1403-11593). The statements presented in this publication are solely the responsibility of the authors and do not necessarily represent the views of PCORI, its board of governors, or its methodology committee. Additional funds for the study were provided by the Division of Allergy and Immunology at Cincinnati Children’s Hospital Medical Center. Disclosure of potential conflict of interest: J. P. Abonia has received payment or honoraria for lectures from Takeda Global Research and Development; has participated on a data safety monitoring board for OctaPharma USA Inc; and has received grants or contracts from Cures Within Reach and Celgene. S. S. Aceves has received consultant fees from Regeneron Pharmaceuticals, AstraZeneca, and Bristol Myers Squibb; has received research funding from Implicit Biosciences; is coinventor of oral viscous budesonide University of California, San Diego, patent Takeda license; and has received educational speaker fees from Sanofi/Genzyme and Regeneron Pharmaceuticals. K. E. Capocelli is employed by and has an equity interest in Alnylam. M. Chehade has served as a consultant for Regeneron Pharmaceuticals, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Nexstone Immunology, Allakos, Shire/Takeda, and Phathom; and has received research funding from Regeneron Pharmaceuticals, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone, and Bristol Myers Squibb. M. H. Collins is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc/Alimentiv Inc, and Shire/Takeda. E. S. Dellon is a consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; has received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; and has received educational grants from Allakos, Aqilion, Holoclara, and Invea. G. T. Furuta serves as CMO for EnteroTrack LLC; and has received research funding from Arena/Pfizer, Holoclara, and the National Institutes of Health (NIH). S. K. Gupta is a consultant for Abbott, Allakos, Adare Pharmaceuticals, DBV Technologies, Gossamer Bio, QOL Medical, Medscape, Receptos/Celgene, and UpToDate; and has received research support from Shire/Takeda. J. Leung is a consultant for Adare, Eli Lilly, AbbVie, Genzyme, Regeneron, Sanofi, and Shire/Takeda; and has received research funding from Adare, Allakos, Celgene, Regeneron, AstraZeneca, and Shire/Takeda. V. A. Mukkada has received consulting fees from Allakos, Regeneron, Sanofi, and Shire/Takeda; has received honoraria for lectures from the American Gastroenterological Association; and serves on an adjudication board for Alladapt. R. D. Pesek is a consultant for Regeneron Pharmaceuticals. T. Shoda has funding from the NIH and is a coinventor of patents owned by Cincinnati Children’s Hospital Medical Center. J. M. Spergel has received grant support from Regeneron Pharmaceuticals/Sanofi, Novartis, the NIH, and Food Allergy Research and Education; is a consultant for Regeneron Pharmaceuticals, Sanofi, Alladapt, Readysetfood, and ARS Pharmacy; and has received royalties from UpToDate. J. B. Wechsler is a consultant for Allakos, Ellodi, Regeneron Pharmaceuticals, Sanofi/Genzyme, AstraZeneca, Celldex, and Invea Therapeutics; and has received clinical trial/research funding from Allakos, Invea Therapeutics, and Sanofi/Regeneron. M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nexstone One, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, Astra Zeneca, Pfizer, GlaxoSmith Kline, Sanofi/Regeneron, Revolo Biotherapeutics, and Guidepoint; and has an equity interest in the first nine listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate. M. E. Rothenberg is an inventor of patents owned by Cincinnati Children’s Hospital. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Eosinophilic esophagitis (EoE) is a progressive type 2 inflammatory disease characterized by symptoms related to esophageal dysfunction and significant esophageal eosinophilic infiltration. It can affect patients from infancy through adulthood. Pediatric EoE has a multidimensional impact on the quality of life of both patients and their families. Nonspecific symptoms mimicking other gastrointestinal conditions, such as food refusal, failure to thrive, and feeding difficulties, may profoundly affect young children's eating skills, growth, and psychosocial status, as well as impact family financial conditions. In adolescence, dysphagia and esophageal food impactions often lead to feeding-related anxiety and influence social lives. Delays in diagnosis, arising from lack of awareness among families and clinicians and compensatory eating behaviors, could increase the risk of fibrostenotic complications, which may ultimately add to the symptom burden. Currently available treatment options include proton pump inhibitors, dietary therapies, swallowed topical steroids, esophageal dilation, and biologic therapy. Despite the efficacy of these approaches, disease burden may be further impacted by their limitations, including poor adherence rates, refractory disease, potential long-term safety concerns, and high costs for care. Thus, there is a need for more timely diagnosis in clinical practice and novel targeted disease-modifying therapies better tailored to treat various phenotypes of EoE, aimed at reducing the physical and psychosocial burdens on patients and their caregivers., (© 2024 The Authors.)

Background: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE)., Objective: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both., Methods: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed., Results: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity., Conclusions: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation., Competing Interests: Disclosure statement Supported by National Institutes of Health (NIH) grant K99/R00 AI158660 (to T.S.) and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR, U54 AI117804), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is cofunded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCATS, and in part by the Intramural Research Program of NIAID. CEGIR is also supported by patient advocacy groups, including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by NCATS and the National Institute of Neurological Disorders and Stroke (NINDS). This project was supported in part by NIH P30 DK078392 (Gene Expression Core, Pathology Research Core, and Confocal Imaging Core) of the Digestive Diseases Research Core Center in Cincinnati. Disclosure of potential conflict of interest: E. S. Dellon is consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/ Bristol Meyers Squibb (BMS), Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio. E. S. Dellon has received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; and has received educational grants from Allakos, Holoclara, and Invea. S. S. Aceves is disease state awareness speaker and consultant for Sanofi/Regeneron, consultant for Ferring Pharma; has research funding from Implicit Biosciences and BMS; and is a coinventor of oral viscous budesonide UCSD patent, Takeda license. M. Chehade served as consultant for Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, BMS, Allakos, Shire/Takeda, Phathom, Recludix Pharma, Nexstone Immunology; and received research funding from Regeneron, Allakos, AstraZeneca, Adare/Ellodi, BMS, Danone, and Shire/Takeda. M. H. Collins is consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, BMS, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene, Regeneron Pharmaceuticals, Robarts Clinical Trials/Alimentiv, Sanofi, and Shire/Takeda. C. M. Davis receives research funding from the NIH/NIAID (U01AI126614, UM2AI130836, U54AI117804), DBV Technologies, Aimmune Therapeutics, Regeneron Pharmaceuticals, Takeda, and Allergenis. G. W. Falk is consultant for Ellodi, Sanofi/Regeneron, BMS/Celgene, Takeda, Ubiquity Bio, and Phathom Pharmaceuticals; and receives research funding from Arena/Pfizer, Ellodi, Sanofi/Regeneron, BMS/Celgene, Takeda, Allakos, Nexteos, and Celldex Therapeutics. G. T. Furuta receives research funding from Pfizer/Arena; is consultant for Sanofi/Regeneron and BMS; and is chief medical officer for EnteroTrack. N. P. Gonsalves is consultant for Allakos, AstraZeneca, BMS, and Sanofi/Regeneron; is speaker for Sanofi/Regeneron; and receives publication royalties from UpToDate. S. K. Gupta is consultant/data safety monitoring board member of Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate; and receives research funding from Allakos, Ellodi, and AstraZeneca. I. Hirano has received research funding from Ellodi/Adare, Allakos, Pfizer/Arena Pharmaceuticals, AstraZeneca, Meritage Pharma, Receptos/Celgene, Sanofi, Regeneron, and Shire/Takeda; and is is consultant for Ellodi/Adare, Allakos, AstraZeneca, BMS/Receptos/Celgene, Calyx/Parexel, EsoCap Biotech, Gossamer Bio, Lilly, Meritage Pharma, Pfizer/Arena Pharmaceuticals, Phathom, Sanofi/Regeneron, and Shire/Takeda. K. A. Peterson is consultant/advisory for AGA, Alladapt, AstraZeneca, Allakos, BMS, Ellodi, Invea, Lucid, Nexstone, WebMD, Peerview, Regeneron, Revolo, Takeda, and WebMD; receives research funding from AstraZeneca, Allakos, Regeneron-Sanofi, Revolo, Adare, Ellodi, BMS, and Celldex; is speaker for AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; has grant support (unrestricted) from Allakos; and has equity in Nexeos Bio. M. A. Pletneva is consultant for Allakos and Sanofi/Regeneron. J. M. Spergel is consultant for Novartis, Regeneron, and Sanofi; and receives grant support from Regeneron and Sanofi. J. B. Wechsler is speaker for Sanofi/Regeneron; and consultant for Sanofi/Regeneron, Celldex, Celgene/Receptos/BMS, Allakos, Ellodi, and AstraZeneca. M. E. Rothenberg is consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, BMS, AstraZeneca, Ellodi Pharma, Glaxo Smith Kline, Sanofi/Regeneron, Revolo Biotherapeutics, and Guidepoint; has equity interest in the first 6 listed; receives royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate; and is an inventor of patents owned by Cincinnati Children’s Hospital Medical Center. T. Shoda is a coinventor of patents owned by Cincinnati Children’s Hospital Medical Center. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Introduction: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study., Methods: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo., Results: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24., Discussion: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Social determinants of health (SDOH) may influence the clinical management of patients with heart failure. Further research is warranted on the relationship between SDOH and Ventricular Assist Device (VAD) therapy for heart failure., Objectives: The purpose of this integrative review was to synthesize the state of knowledge on the intersection of SDOH with VAD therapy., Methods: Guided by Whittemore and Knafl's methodology, this literature search captured three concepts of interest including VAD therapy, SDOH, and their domains of intersection with patient selection, decision-making, treatment outcome, and resource allocation. CINAHL, Embase, PsycINFO, PubMed, and Web of Science were searched in March 2023. Articles were included if they were peer-reviewed publications in English, published between 2006 and 2023, conducted in the United States, and examined VAD therapy in the context of adult patients (age ≥ 18 years)., Results: 22 quantitative studies meeting the inclusion criteria informed the conceptualization of SDOH using the Healthy People 2030 framework. Four themes captured how the identified SDOH intersected with different processes relating to VAD therapy: patient decision-making, healthcare access and resource allocation, patient selection, and treatment outcomes. Most studies addressed the intersection of SDOH with healthcare access and treatment outcomes., Conclusion: This review highlights substantial gaps in understanding how SDOH intersect with patient and patient selection for VAD. More research using mixed methods designs is warranted. On an institutional level, addressing bias and discrimination may have mitigated health disparities with treatment outcomes, but further research is needed for implementing system-wide change. Standardized assessment of SDOH is recommended throughout clinical practice from patient selection to outpatient VAD care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood., Objective: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis., Methods: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms., Results: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden., Conclusion: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Patients with non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) are prone to nutritional deficiencies due to food-avoidant behaviors, malabsorption, and high nutrition impact symptoms. Nutrient deficiencies correspond to the segment, depth, and extent of the gastrointestinal tract involved and can impact organs distant from the gut. Patients with non-EoE EGIDs are often atopic, and some appear to respond to dietary avoidance of specific food allergens. Tests to identify food triggers other than response to elimination diets are lacking. Dietary restriction therapy should be considered in such patients and is best implemented through a multidisciplinary approach to avoid nutritional complications., Competing Interests: Disclosure M. Chehade is currently serving or has served as consultant for Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Nexstone Immunology, Allakos, Shire/Takeda, and Phathom, and is currently receiving or has received research funding from Regeneron, United States, Allakos, Shire/Takeda, AstraZeneca, United Kingdom, Adare/Ellodi, Bristol-Myers Squibb, United States, Danone, v. B. Doerfler has served on speakers bureaus for Nutricia North America, on advisory boards for Trellus Health LLC, and received honoraria from PRIMED CME and ACHL Healthcare. D. Atkins has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis., Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics., Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines., Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines., Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs., Competing Interests: Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Disease Research, National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Diabetes and Digestive and Kidney Diseases, NCATS, and patient advocacy groups including the American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). This work was also funded in part by the Division of Intramural Research, NIAID, National Institutes of Health. Disclosure of potential conflict of interest: M. Chehade served as consultant for Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, Bristol Myers Squibb, Phathom, Recludix Pharma, and Nexstone Immunology; and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone, and Bristol Myers Squibb. A. B. Muir has served on medical advisory board for Bristol Myers Squibb and Nexstone Immunology; and has received research funding from Morphic. M. H. Collins has received research funding from AstraZeneca, Ception, GSK, Meritage Pharma Inc, Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company; and is consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc/Alimentiv Inc and Shire, a Takeda company. C. M. Davis has received research funding from the National Institutes of Health/National Institute of Allergy and Infectious Disease (Consortium of Food Allergy Research/Consortium of Eosinophilic Gastrointestinal Researchers), DBV Technologies, DBV, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis. G. T. Furuta is chief medical officer at EnteroTrack; consultant for Shire/Takeda; and has received grant funding from Arena and Holoclara. S. Gupta is consultant/data safety and monitoring board member or author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate; and has received research support from Allakos, Ellodi, and AstraZeneca. P. Khoury has received research funding from American Partnership for Eosinophilic Disorders. K. A. Peterson is consultant or served as advisor for AGA, Alladapt, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Lucid, Nexstone, Peerview, Regeneron, Takeda, and WebMD; has received research support from AstraZeneca, Allakos, Adare, Regeneron-Sanofi, and Revolo; served as speaker for AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; received grant support (unrestricted) from Allakos and Chobani; and holds equity in Nexeos Bio. E. T. Jensen has received consultant fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Introduction: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined., Methods: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls., Results: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months)., Discussion: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: With more than 103 million cases and 1.1 million deaths, the COVID-19 pandemic has had devastating consequences for the health system and the well-being of the entire US population. The Rare Diseases Clinical Research Network funded by the National Institutes of Health was strategically positioned to study the impact of the pandemic on the large, vulnerable population of people living with rare diseases (RDs)., Objective: This study was designed to describe the characteristics of COVID-19 in the RD population, determine whether patient subgroups experienced increased occurrence or severity of infection and whether the pandemic changed RD symptoms and treatment, and understand the broader impact on respondents and their families., Methods: US residents who had an RD and were <90 years old completed a web-based survey investigating self-reported COVID-19 infection, pandemic-related changes in RD symptoms and medications, access to care, and psychological impact on self and family. We estimated the incidence of self-reported COVID-19 and compared it with that in the US population; evaluated the frequency of COVID-19 symptoms according to self-reported infection; assessed infection duration, complications and need for hospitalization; assessed the influence of the COVID-19 pandemic on RD symptoms and treatment, and whether the pandemic influenced access to care, special food and nutrition, or demand for professional psychological assistance., Results: Between May 2, 2020, and December 15, 2020, in total, 3413 individuals completed the survey. Most were female (2212/3413, 64.81%), White (3038/3413, 89.01%), and aged ≥25 years (2646/3413, 77.53%). Overall, 80.6% (2751/3413) did not acquire COVID-19, 2.08% (71/3413) acquired it, and 16.58% (566/3413) did not know. Self-reported cases represented an annual incidence rate of 2.2% (95% CI 1.7%-2.8%). COVID-19 cases were more than twice the expected (71 vs 30.3; P<.001). COVID-19 was associated with specific symptoms (loss of taste: odds ratio [OR] 38.9, 95% CI 22.4-67.6, loss of smell: OR 30.6, 95% CI 17.7-53.1) and multiple symptoms (>9 symptoms vs none: OR 82.5, 95% CI 29-234 and 5-9: OR 44.8, 95% CI 18.7-107). Median symptom duration was 16 (IQR 9-30) days. Hospitalization (7/71, 10%) and ventilator support (4/71, 6%) were uncommon. Respondents who acquired COVID-19 reported increased occurrence and severity of RD symptoms and use or dosage of select medications; those who did not acquire COVID-19 reported decreased occurrence and severity of RD symptoms and use of medications; those who did not know had an intermediate pattern. The pandemic made it difficult to access care, receive treatment, get hospitalized, and caused mood changes for respondents and their families., Conclusions: Self-reported COVID-19 was more frequent than expected and was associated with increased prevalence and severity of RD symptoms and greater use of medications. The pandemic negatively affected access to care and caused mood changes in the respondents and family members. Continued surveillance is necessary., (©Maurizio Macaluso, Marc E Rothenberg, Thomas Ferkol, Pierce Kuhnell, Henry J Kaminski, David W Kimberlin, Michael Benatar, Mirna Chehade, The Principal Investigators of the Rare Diseases Clinical Research Network – Cycle 4. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.02.2024.)

Although eosinophilic gastrointestinal diseases, including eosinophilic esophagitis, have been described over the past 2 to 3 decades, barriers to diagnosis and treatment are common and compounded by issues related to social determinants of health, race, ethnicity, and access to care. These barriers contribute to delays in diagnosis, resulting in persistent inflammation in the gastrointestinal tract, which can have significant consequences, including fibrostenotic complications in adults, failure to thrive in children, and decreased quality of life in all affected patients. In this commentary, we summarize gaps in knowledge regarding the epidemiology of eosinophilic gastrointestinal diseases, highlight barriers to diagnosis, discuss potential approaches based on best practices in other atopic and chronic gastrointestinal diseases, and provide recommendations for reducing barriers to timely diagnosis of eosinophilic gastrointestinal diseases in underserved populations., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Introduction: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs., Methods: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment., Results: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed., Conclusion: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Basal zone hyperplasia (BZH) and dilated intercellular spaces (DISs) are thought to contribute to the clinical manifestations of eosinophilic esophagitis (EoE); however, the molecular pathways that drive BZH remain largely unexplored., Objective: We sought to define the role of IL-13-induced transcriptional programs in esophageal epithelial proliferation in EoE., Methods: We performed RNA sequencing, bioinformatics, Western blot, reverse transcriptase quantitative PCR, and histologic analyses on esophageal biopsies from healthy control and patients with EoE, primary esophageal cells derived from patients with EoE, and IL-13-stimulated esophageal epithelial keratinocytes grown at the air-liquid interface (EPC2-ALI). Genetic (shRNA) and pharmacologic (proteolysis-targeting chimera degrader) approaches and in vivo model of IL-13-induced esophageal epithelial remodeling (Krt5-rtTA x tetO-IL-13Tg) were used to define the role of signal transducer and activator of transcription 3 (STAT3) and STAT6 and secreted frizzled-related protein 1 (SFRP1) in esophageal epithelial proliferation., Results: RNA-sequencing analysis of esophageal biopsies (healthy control vs EoE) and EPC2-ALI revealed 82 common differentially expressed genes that were enriched for putative STAT3 target genes. In vitro and in vivo analyses revealed a link between IL-13-induced STAT3 and STAT6 phosphorylation, SFRP1 mRNA expression, and esophageal epithelial proliferation. In vitro studies showed that IL-13-induced esophageal epithelial proliferation was STAT3-dependent and regulated by the STAT3 target SFRP1. SFRP1 mRNA is increased in esophageal biopsies from patients with active EoE compared with healthy controls or patients in remission and identifies an esophageal suprabasal epithelial cell subpopulation that uniquely expressed the core EoE proinflammatory transcriptome genes (CCL26, ALOX15, CAPN14, ANO1, and TNFAIP6)., Conclusions: These studies identify SFRP1 as a key regulator of IL-13-induced and STAT3-dependent esophageal proliferation and BZH in EoE and link SFRP1 + esophageal epithelial cells with the proinflammatory and epithelial remodeling response in EoE., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) has a detrimental effect on health-related quality of life (HRQOL). The Eosinophilic Esophagitis Impact Questionnaire (EoE-IQ) is a novel patient-reported outcome (PRO) measure assessing the impact of EoE on HRQOL. To assess suitability of the EoE-IQ, its measurement properties were evaluated., Methods: Using baseline and week 24 data from the pivotal, randomized, placebo-controlled, multinational phase 3 R668-EE-1774 trial (NCT03633617) of dupilumab, we evaluated EoE-IQ's measurement properties (including reliability, construct and known-groups validity, and ability to detect change) and established the threshold for change in scores that can be considered clinically meaningful., Results: The analysis population comprised 239 adults and adolescents with EoE. Mean age was 28.1 (standard deviation, 13.14) years; 63.6% were male, and 90.4% were White. Reliability estimates for the EoE-IQ average score exceeded acceptable thresholds for patients who were stable as indicated by ratings of Patient Global Impression of Severity (PGIS) and Change (PGIC) (intraclass correlation coefficients, 0.75 and 0.81). Construct validity correlations with other EoE-specific PRO scores were moderate at baseline (|r|= 0.44-0.60) and moderate to strong at week 24 (|r|= 0.61-0.72). In known-groups analysis, EoE-IQ average score discriminated among groups of patients at varying EoE severity levels defined by PGIS scores. A ≥ 0.6-point reduction in EoE-IQ average score (where scores range from 1 to 5, with higher scores indicating worse HRQOL) from baseline to week 24 can be considered clinically meaningful., Conclusions: The EoE-IQ's measurement properties are acceptable, making it a valid, reliable measure of the HRQOL impacts of EoE among adults and adolescents., Trial Registration: ClinicalTrials.gov, NCT03633617. Registered August 14, 2018, https://clinicaltrials.gov/study/NCT03633617 ., (© 2023. The Author(s).)

Background: Long-term management options that specifically target the underlying inflammation in eosinophilic oesophagitis are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13; we aimed to assess its long-term efficacy and safety in adults and adolescents with eosinophilic oesophagitis enrolled in part B of the LIBERTY EoE TREET study who continued to part C (part B-C)., Methods: LIBERTY EoE TREET was a three-part, double-blind, randomised, placebo-controlled, phase 3 study conducted at 65 hospitals and private clinics across ten countries in Australia, Canada, Europe, and the USA. Adults or adolescents (aged ≥12 years) with a diagnosis of eosinophilic oesophagitis by endoscopic biopsy (peak oesophageal intraepithelial eosinophil count ≥15 eosinophils per high-power field [eos/hpf]) from at least one oesophageal region despite 8 weeks of high-dose proton-pump inhibitors (PPIs) and a Dysphagia Symptom Questionnaire (DSQ) score of at least 10 at baseline were eligible. In part B, patients were randomly (1:1:1) assigned to receive subcutaneous dupilumab 300 mg either weekly or every 2 weeks or weekly placebo until week 24. Randomisation was done centrally by interactive voice response system/web response system (IVRS/IWRS) in blocks and stratified according to age (<18 years vs ≥18 years) and use of PPI at randomisation (yes vs no). Patients, study sponsors, and investigators involved in the study were masked to the randomisation outcome. Eligible patients who received placebo in part B and continued to part C were randomly assigned again (1:1) to either weekly dupilumab (placebo/weekly dupilumab group) or dupilumab every 2 weeks (placebo/dupilumab every 2 weeks), with matching placebo alternating with dupilumab doses. Patients who were randomly assigned to one of the dupilumab dose regimens in part B remained on the same regimen in part C for an additional 28 weeks (weekly dupilumab/weekly dupilumab group or dupilumab every 2 weeks/dupilumab every 2 weeks group). Treatment assignment in part C was managed by IVRS/IWRS to maintain blinding of treatment assignment in part B. The primary endpoint of this trial has been reported; here, we report the week 52 outcomes of part B-C. Efficacy and safety analyses were done in the part C safety-analysis set, which included all patients who were randomised in part B, entered part C, and received any study drug in part C. This completed trial is registered with ClinicalTrials.gov, number NCT03633617., Findings: Between Aug 12, 2019, and March 11, 2021, 240 patients were randomly assigned into part B, of whom 227 (74 in placebo group, 74 in weekly dupilumab group, and 79 in dupilumab every 2 weeks group) continued into part B-C and were included in the current analysis. 37 patients switched from placebo to weekly dupilumab, and 37 from placebo to dupilumab every 2 weeks; 74 patients continued on weekly dupilumab and 79 continued on dupilumab every 2 weeks. Of the patients who entered part B-C, 75 (33%) were adolescents, 145 (64%) male, 82 (36%) female, and 206 (91%) White. At week 52, 55 (85%) patients in the weekly dupilumab/weekly dupilumab group, 25 (68%) in the placebo/weekly dupilumab group, 54 (74%) in the every 2 weeks dupilumab/every 2 weeks dupilumab group, and 23 (72%) in the placebo/every 2 weeks dupilumab group achieved a peak oesophageal intraepithelial eosinophil count of 6 eos/hpf or less. Mean percent change from part B baseline in peak eosinophil count was -95·9% (95% CI -96·9 to -94·9) in the weekly dupilumab/weekly dupilumab group, -84·2% (-98·3 to -70·2) in the placebo/weekly dupilumab group, -84·8% (-94·3 to -75·2) in the every 2 weeks dupilumab/every 2 weeks dupilumab group, and -91·2% (-95·9 to -86·5) in the placebo/every 2 weeks dupilumab group at week 52. At week 52, mean change from part B baseline in eosinophilic oesophagitis Histology Scoring System (HSS) grade score was -1·0 point (95% CI -1·1 to -0·9) in the weekly dupilumab/weekly dupilumab group and -0·9 points (-1·0 to -0·8) in the placebo/weekly dupilumab group; mean change in eosinophilic oesophagitis HSS stage score was -0·9 points (-1·0 to -0·8) in the weekly dupilumab/weekly dupilumab group and -0·9 points (-1·0 to -0·8) in the placebo/weekly dupilumab group. Similar improvements were observed in the every 2 weeks dupilumab groups. Mean absolute change from part B baseline in DSQ score was -30·3 points (95% CI -34·5 to -26·1) in the weekly dupilumab/weekly dupilumab group, -27·3 points (-32·1 to -22·4) in the placebo/weekly dupilumab group, -20·9% (-25·4 to -16·3) in the every 2 weeks dupilumab/every 2 weeks dupilumab group, and -23·7% (-29·1 to -18·3) in the placebo/every 2 weeks dupilumab group at week 52. Mean change from part B baseline in endoscopic reference score was -5·4 points (95% CI -6·1 to -4·6) in the weekly dupilumab/weekly dupilumab group, -6·1 points (-7·3 to -4·9) in the placebo/weekly dupilumab group, -5·2% (-6·0 to -4·4) in the every 2 weeks dupilumab/every 2 weeks dupilumab group, and -4·3% (-5·4 to -3·1) in the placebo/every 2 weeks dupilumab group at week 52. During part B-C, one (3%) patient in the placebo/weekly dupilumab group, one (1%) in the weekly dupilumab/weekly dupilumab group, and one (3%) in the placebo/every 2 weeks dupilumab group received rescue medication. One (3%) patient in the placebo/every 2 weeks dupilumab group and one (1%) in the dupilumab every 2 weeks/dupilumab every 2 weeks group underwent a rescue oesophageal dilation procedure. The most common treatment-emergent adverse events were injection-site reactions (ten [14%] in the weekly dupilumab/weekly dupilumab group and four [11%] in the placebo/weekly dupilumab group)., Interpretation: Improvements in histological, symptomatic, endoscopic, and molecular features of eosinophilic oesophagitis observed after 24 weeks of weekly dupilumab treatment were maintained or continued to improve to week 52. These findings reinforce the importance of weekly dupilumab, rather than every 2 weeks, for the improvement of symptoms in adults and adolescents with eosinophilic oesophagitis., Funding: Sanofi and Regeneron Pharmaceuticals Inc., Competing Interests: Declaration of interests MER has acted as a consultant for Allakos, AstraZeneca, BMS, Celldex, ClostraBio, Ellodi Pharmaceuticals, GSK, Guidepoint, Nextstone One, PulmOne, Regeneron Pharmaceuticals Inc, Revolo, Sanofi, Santa Ana Bio, Serpin Pharma, and Spoon Guru; holds equity interest in Celldex, ClostraBio, Nextstone One, PulmOne, Santa Ana Bio, Serpin Pharma, and Spoon Guru; has received royalties from Mapi Research Trust (for PEESSv2), Teva Pharmaceuticals (for reslizumab), and UpToDate; and is the inventor of patents owned by Cincinnati Children's Hospital. ESD has acted as a consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, Gossamer Bio, GSK, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron Pharmaceuticals Inc, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; has received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, Celgene/Receptos/BMS, GSK, Meritage, Miraca, Nutricia, Regeneron Pharmaceuticals Inc, Revolo, and Shire/Takeda; and has received educational grants from Allakos, Holoclara, and Invea. MHC has acted as a consultant for Allakos, Arena, AstraZeneca, BMS, Calypso, EsoCap, GSK, Regeneron Pharmaceuticals Inc, and Shire; has received licence fees for use of the eosinophilic oesophagitis Histology Scoring System; has received honorarium from Sanofi; and her institution has received research funding from AstraZeneca, Receptos/Cellgene/BMS, and Regeneron Pharmaceuticals Inc. IH has acted as a consultant for Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Dermavant, Eli Lilly, EsoCap, Gossamer Bio, GSK, Nexstone Immunology, Parexel/Calyx, Phathom, Receptos/BMS, Regeneron Pharmaceuticals Inc, Sanofi, and Shire/Takeda; has received payment or honoraria from Regeneron Pharmaceuticals Inc and Sanofi; and has received research funding from Adare/Ellodi, Allakos, AstraZeneca, Receptos/BMS, Regeneron Pharmaceuticals Inc, and Shire/Takeda. MC has acted as a consultant for Adare/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix, Regeneron Pharmaceuticals Inc, Sanofi, and Shire/Takeda; and has received research funding from Adare/Ellodi, Allakos, AstraZeneca, Cellgene/BMS, Danone, Regeneron Pharmaceuticals Inc, and Shire/Takeda. AJB has acted as a consultant for Alimentiv, Aquilon, AstraZeneca, Dr Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc, and Sanofi; has received research or grant support from Bayer, Dr Falk Pharma, Norgine, Nutricia, Regeneron Pharmaceuticals Inc, Sanofi, Side Sleep Technologies, and Thelial; has received lecture fees from or has served as a member of the speakers bureaux for Alimentiv, Aquilon, AstraZeneca, Dr Falk Pharma, Eupraxia, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc, and Sanofi. AJL has acted as a consultant for Dr Falk Pharma and EsoCap; and has received research funding from Dr Falk Pharma and Regeneron Pharmaceuticals Inc. JMS has acted as a consultant for Allakos, DBV Technologies, Novartis, Regeneron Pharmaceuticals Inc, and Shire/Takeda; and has received grant support from DBV Technologies and Regeneron Pharmaceuticals Inc. XS, JDH, EM, EMcC, XL, JM, and AS are employees and shareholders in Regeneron Pharmaceuticals Inc. LPM, EL, and LG are employees and may hold stock or stock options in Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background & Aims: Patients with poorly controlled eosinophilic esophagitis (EoE) may require unplanned emergency department (ED) visits for the management of dysphagia or food impactions. We evaluated the epidemiologic burden of EoE on ED utilization in the United States., Methods: Data from the US Nationwide Emergency Department Sample were used to estimate weighted annual EoE-associated ED visits from 2009 to 2019. Temporal trends in population-adjusted rates of EoE visits were assessed using joinpoint regression. Autoregressive integrated moving average models were used to project EoE-associated ED visits to 2030. We also evaluated endoscopic utilization, requirement for hospitalization, and ED-related charges in patients with EoE presenting to the ED., Results: A total of 11,125 unweighted (49,507 weighted) ED visits for EoE were included (69.0% male; mean age, 32.4 y). The annual volume of EoE-associated ED visits increased from 2934 (95% CI, 2437-3431) in 2009 to 8765 (95% CI, 7514-10,015) in 2019, and is projected to reach 15,445 (95% prediction interval, 14,672-16,218) by 2030. From 2009 to 2019, the number of EoE-associated ED visits increased by an average of 11.5% per year (95% CI, 10.3%-12.7%). The proportion of patients admitted to the hospital from the ED decreased from 25.6% in 2009 to 2011 to 14.0% in 2017 to 2019. Half of EoE patients presenting to the ED required an endoscopy, and nearly 40% required an esophageal foreign body removal. Total mean inflation-adjusted charges for an EoE-associated ED visit were $9025 US dollars in 2019., Conclusions: The volume of EoE-associated ED visits tripled between 2009 and 2019 and is projected to further double by 2030. This represents a substantial burden of unanticipated health care resource utilization and highlights a potential opportunity to optimize outpatient EoE care., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The availability of an ever-increasing diversity of prokaryotic genomes and metagenomes represents a major opportunity to understand and decipher the mechanisms behind the functional diversification of microbial biosynthetic pathways. However, it remains unclear to what extent a pathway producing a specific molecule from a specific precursor can diversify. In this study, we focus on the biosynthesis of ubiquinone (UQ), a crucial coenzyme that is central to the bioenergetics and to the functioning of a wide variety of enzymes in Eukarya and Pseudomonadota (a subgroup of the formerly named Proteobacteria). UQ biosynthesis involves three hydroxylation reactions on contiguous carbon atoms. We and others have previously shown that these reactions are catalyzed by different sets of UQ-hydroxylases that belong either to the iron-dependent Coq7 family or to the more widespread flavin monooxygenase (FMO) family. Here, we combine an experimental approach with comparative genomics and phylogenetics to reveal how UQ-hydroxylases evolved different selectivities within the constrained framework of the UQ pathway. It is shown that the UQ-FMOs diversified via at least three duplication events associated with two cases of neofunctionalization and one case of subfunctionalization, leading to six subfamilies with distinct hydroxylation selectivity. We also demonstrate multiple transfers of the UbiM enzyme and the convergent evolution of UQ-FMOs toward the same function, which resulted in two independent losses of the Coq7 ancestral enzyme. Diversification of this crucial biosynthetic pathway has therefore occurred via a combination of parallel evolution, gene duplications, transfers, and losses., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background & Aims: The nature of the involvement of esophageal tissue in eosinophilic esophagitis (EoE) is unclear. We estimated the intrabiopsy site agreements of the EoE Histologic Scoring System (EoEHSS) scores for the grade (degree) and stage (extent) of involvement of the esophageal epithelial and lamina propria and examined if the EoE activity status influenced the intrabiopsy site agreement., Methods: Demographic, clinical, and EoEHSS scores collected as part of the prospective Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages study were analyzed. A weighted Cohen's kappa agreement coefficient (k) was used to calculate the pairwise agreements for proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites, separately for grade and stage scores, for each of the 8 components of EoEHSS. A k > 0.75 was considered uniform involvement. Inactive EoE was defined as fewer than 15 eosinophils per high-powered field., Results: EoEHSS scores from 1263 esophageal biopsy specimens were analyzed. The k for the stage of involvement of the dilated intercellular spaces across all 3 sites in inactive EoE was consistently greater than 0.75 (range, 0.87-0.99). The k for lamina propria fibrosis was greater than 0.75 across some of the biopsy sites but not across all 3. Otherwise, the k for all other features, for both grade and stage, irrespective of the disease activity status, was 0.75 or less (range, 0.00-0.74)., Conclusions: Except for the extent of involvement of dilated intercellular spaces in inactive EoE, the remaining epithelial features and lamina propria are involved unevenly across biopsy sites in EoE, irrespective of the disease activity status. This study enhances our understanding of the effects of EoE on esophageal tissue pathology., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Context.—: Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists., Objective.—: To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies., Design.—: Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively., Results.—: Pathologists correctly diagnosed most noneosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C., Conclusions.—: Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs., (© 2023 College of American Pathologists.)

For food-allergic patients, hypoallergenic formulas (HFs) are medically indicated, often a primary component of the diet and essential for patient safety, health, nutrition, and overall well-being. Yet, food allergy is not included among the conditions mandated for coverage under federal health programs and private health insurance. The 2022 infant formula crisis has affected many North American families and has particularly influenced patients with food allergies who rely on a limited number of safe HF brands to safely meet their nutritional needs for growth and development. The current formula shortage further highlights the longstanding difficulties faced by families with food allergies in accessing HF. Within this context, this article focuses on chronic barriers faced by patients with food allergies in accessing HF and proposes potential solutions. Legislation is desperately needed to address HF affordability through changes in insurance reimbursement and disparities in access to HF among individuals with food allergy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee's inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR's ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research., Competing Interests: MC received consultant fees from Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Allakos, Shire/Takeda, Phathom, and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone. GFuruta serves as CMO for EnteroTrack and received research funding from Arena/Pfizer, Holoclara, and NIH. JPA received payment or honoraria for lectures from Takeda Global Research and Development, participated on a Data Safety Monitoring Board for OctaPharma USA, Inc., and received grants or contracts from Cures Within Reach and Celgene. SA received consultant fees for Regeneron, AstraZeneca, Bristol Meyers Squibb, research funding from Implicit Biosciences, is co-inventor of oral viscous budesonide UCSD patent Takeda license, and received educational speaker fees from Sanofi/Genzyme, Regeneron. MHC received research funding from AstraZeneca, Ception, GlaxoSithKline, Meritage Pharma Inc., Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company, and is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company. ESD received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda, consultant fees from Abbott, Abbvie, Adare/ Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio, and educational grants from Allakos, Holoclara, Invea. GFalk received consultant fees for Adare/Ellodi, Allakos, Bristol Myers Squibb/Celgene, Lucid, Nexstone, Phathom, Regeneron/Sanofi, Shire/Takeda, Upstream Bio, and research support from Adare/Ellodi, Allakos, Arena/Pfizer, Bristol Myers Squibb/Celgene, Lucid, Nexteos, Regeneron/Sanofi, Shire/Takeda. SG is a Consultant/DSMB member/author for Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate, and received research support from Allakos, Ellodi, AstraZeneca. ETJ received consulting fees for Regeneron Pharmaceuticals and Jazz Pharmaceuticals. PK received funding from APFED. DM has received past honoraria from GSK for awareness activities unrelated to this publication and/or disease state. MR is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Bristol Myers Squibb, Astra Zeneca, Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first seven listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. MR is an inventor of patents owned by Cincinnati Children’s Hospital. JS received grant support from Regeneron/Sanofi, Novartis, NIH, FARE, consulting fees from Regeneron, Sanofi, Alladapt, Readysetfood, ARS Pharmacy, and royalties from Uptodate. ABM received research funding from Morphic and served on medical advisory board for Bristol Myers Squib and Nextone Immunology. VM received consultant fees from Allakos, Regeneron, Sanofi, and Shire/Takeda, and served on an adjudication board for Alladapt. CD received research funding from DBV Technologies, Food Allergy Research and Education, Allergenis, Regeneron Pharmaceuticals, Pfizer, and consultant or advisory board fees for Aimmune Therapeutics. JBW has received consultant fees from Allakos, Ellodi, Regeneron, Sanofi/Genzyme, AstraZeneca, and Invea Therapeutics, and clinical trial/research funding from Allakos, Invea Therapeutics, and Sanofi-Regeneron. BLW, DDB, AK, GE, GH, KK, EK, SKyle, PM, PM-K, CS, MJS, G-YY, KS, NM, SKesh, PB, MS, AZ, AP, AH, and GF have no conflicts of interest to declare., (© The Author(s), 2023.)

Background: Eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease, is linked to multiple genetic risk factors, but studies have focused on populations of European ancestry. Few studies have assessed Black or African American (AA) populations for loci involved in EoE susceptibility., Objective: We performed admixture mapping (AM) and genome-wide association study (GWAS) of EoE using participants from AA populations., Methods: We conducted AM and GWAS of EoE using 137 EoE cases and 1465 healthy controls from the AA population. Samples were genotyped using molecular evolutionary genetics analysis (MEGA). Genotype imputation was carried out with the Consortium on Asthma Among African-Ancestry Populations in the Americas (CAAPA) reference panel using the Michigan Imputation Server. Global and local ancestry inference was carried out, followed by fine mapping and RNA sequencing. After quality control filtering, over 6,000,000 variants were tested by logistic regression adjusted for sex, age, and global ancestry., Results: The global African ancestry proportion was found to be significantly lower among cases than controls (0.751 vs 0.786, P = .012). Case-only AM identified 3 significant loci (9p13.3, 12q24.22-23, and 15q11.2) associated with EoE, of which 12q24.22-23 and 9p13.3 were further replicated in the case-control analysis, with associations observed with African ancestry. Fine mapping and multiomic functional annotations prioritized the variants rs11068264 (FBXW8) and rs7307331 (VSIG10) at 12q24.23 and rs2297879 (ARHGEF39) at 9p13.3. GWAS identified 1 genome-wide significant locus at chromosome 1p22.3 (rs17131726, DDAH1) and 10 other suggestive loci. Most GWAS variants were low-frequency African ancestry-specific variants. RNA sequencing revealed that esophageal DDAH1 and VSIG10 were downregulated and ARHGEF39 upregulated among EoE cases., Conclusions: GWAS and AM for EoE in AA revealed that African ancestry-specific genetic susceptibility loci exist at 1p22.3, 9p13.3, and 12q24.23, providing evidence of ancestry-specific inheritance of EoE. More independent genetic studies of different ancestries for EoE are needed., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Empirical elimination diets are effective for achieving histological remission in eosinophilic oesophagitis, but randomised trials comparing diet therapies are lacking. We aimed to compare a six-food elimination diet (6FED) with a one-food elimination diet (1FED) for the treatment of adults with eosinophilic oesophagitis., Methods: We conducted a multicentre, randomised, open-label trial across ten sites of the Consortium of Eosinophilic Gastrointestinal Disease Researchers in the USA. Adults aged 18-60 years with active, symptomatic eosinophilic oesophagitis were centrally randomly allocated (1:1; block size of four) to 1FED (animal milk) or 6FED (animal milk, wheat, egg, soy, fish and shellfish, and peanut and tree nuts) for 6 weeks. Randomisation was stratified by age, enrolling site, and gender. The primary endpoint was the proportion of patients with histological remission (peak oesophageal count <15 eosinophils per high-power field [eos/hpf]). Key secondary endpoints were the proportions with complete histological remission (peak count ≤1 eos/hpf) and partial remission (peak counts ≤10 and ≤6 eos/hpf) and changes from baseline in peak eosinophil count and scores on the Eosinophilic Esophagitis Histology Scoring System (EoEHSS), Eosinophilic Esophagitis Endoscopic Reference Score (EREFS), Eosinophilic Esophagitis Activity Index (EEsAI), and quality of life (Adult Eosinophilic Esophagitis Quality-of-Life and Patient Reported Outcome Measurement Information System Global Health questionnaires). Individuals without histological response to 1FED could proceed to 6FED, and those without histological response to 6FED could proceed to swallowed topical fluticasone propionate 880 μg twice per day (with unrestricted diet), for 6 weeks. Histological remission after switching therapy was assessed as a secondary endpoint. Efficacy and safety analyses were done in the intention-to-treat (ITT) population. This trial is registered on ClinicalTrials.gov, NCT02778867, and is completed., Findings: Between May 23, 2016, and March 6, 2019, 129 patients (70 [54%] men and 59 [46%] women; mean age 37·0 years [SD 10·3]) were enrolled, randomly assigned to 1FED (n=67) or 6FED (n=62), and included in the ITT population. At 6 weeks, 25 (40%) of 62 patients in the 6FED group had histological remission compared with 23 (34%) of 67 in the 1FED group (difference 6% [95% CI -11 to 23]; p=0·58). We found no significant difference between the groups at stricter thresholds for partial remission (≤10 eos/hpf, difference 7% [-9 to 24], p=0·46; ≤6 eos/hpf, 14% [-0 to 29], p=0·069); the proportion with complete remission was significantly higher in the 6FED group than in the 1FED group (difference 13% [2 to 25]; p=0·031). Peak eosinophil counts decreased in both groups (geometric mean ratio 0·72 [0·43 to 1·20]; p=0·21). For 6FED versus 1FED, mean changes from baseline in EoEHSS (-0·23 vs -0·15; difference -0·08 [-0·21 to 0·05]; p=0·23), EREFS (-1·0 vs -0·6; difference -0·4 [-1·1 to 0·3]; p=0·28), and EEsAI (-8·2 vs -3·0; difference -5·2 [-11·2 to 0·8]; p=0·091) were not significantly different. Changes in quality-of-life scores were small and similar between the groups. No adverse event was observed in more than 5% of patients in either diet group. For patients without histological response to 1FED who proceeded to 6FED, nine (43%) of 21 reached histological remission; for patients without histological response to 6FED who proceeded to fluticasone propionate, nine (82%) of 11 reached histological remission., Interpretation: Histological remission rates and improvements in histological and endoscopic features were similar after 1FED and 6FED in adults with eosinophilic oesophagitis. 6FED had efficacy in just less than half of 1FED non-responders and steroids had efficacy in most 6FED non-responders. Our findings indicate that eliminating animal milk alone is an acceptable initial dietary therapy for eosinophilic oesophagitis., Funding: US National Institutes of Health., Competing Interests: Declaration of interests NG receives royalties from UpToDate; is a consultant for Allakos, Regeneron-Sanofi, AstraZeneca, AbbVie, Takeda, Knopp, Bristol Meyers Squibb, and Nutricia; and has received payment or honoraria for speaker's bureaus for Takeda and Regeneron-Sanofi. ESD has received research support from Ellodi (formerly Adare), Allakos, Arena, AstraZeneca, GlaxoSmithKline, Meritage, Miraca, Nutricia, Celgene (formerly Receptos and a subsidiary of Bristol Myers Squibb), Regeneron, Revolo, and Shire (a subsidiary of Takeda); is a consultant for Abbott, AbbVie, Ellodi, Aimmune, Akesobio, Allakos, Amgen, Arena, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene, Celldex, Eli Lilly, EsoCap, GlaxoSmithKline, Gossamer Bio, Invea, Landos, Lucid Diagnostics, Morphic, Nutricia, Calyx (formerly Parexel), Phathom, Regeneron, Revolo, Alimentiv (formerly Robarts), Salix, Sanofi, Shire, and Target RWE; and has education grants with Allakos, Banner, and Holoclara. DAK has received consulting fees and payments for presentations from Celgene; has served on a data and safety monitoring board at the University of North Carolina; and serves on the governing board of the American Gastroenterological Association. JPA has received research support from Cures Within Reach and Celgene; has received payment or honoraria for lectures from Takeda; and has served on a data and safety monitoring board for Octapharma USA. SSA has received research support from Implicit Biosciences and the Campaign Urging Research for Eosinophilic Disease (CURED) Foundation; has received consulting fees from Bristol Meyers Squibb, Regeneron-Sanofi, and AstraZeneca; has received payment for presentations or events from Regeneron-Sanofi; and receives patent royalties and is co-inventor of oral viscous budesonide, patented by University of California San Diego and licensed by Shire. KEC is employed by and has an equity interest in Alnylam. MC has received consulting fees from Regeneron, Allakos, Ellodi, Shire, AstraZeneca, Sanofi, Bristol Myers Squibb, Phathom; has received research support from Regeneron, Allakos, Shire, AstraZeneca, Ellodi, and Danone; and holds leadership roles in the American Partnership for Eosinophilic Disorders (APFED) and the American Academy of Allergy, Asthma and Immunology (AAAAI). AC has received research support from Aimmune and DBV Technologies; has served on a data and safety monitoring board for Regeneron, Sanofi, AstraZeneca, and DBV Technologies; and holds leadership roles in the AAAAI, European Academy of Allergy and Clinical Immunology, and American College of Allergy, Asthma and Immunology. MHC is a consultant for Allakos, AstraZeneca, Bristol Myers Squibb, Esocap, GlaxoSmithKline, Shire, Regeneron, Celgene, Sanofi, and Ellodi; has received research funding from Shire, Regeneron, Celgene, and AstraZeneca; holds leadership roles in the APFED, CURED Foundation, and The International Gastrointestinal Eosinophil Researchers; and has received travel support from Regeneron and Celgene. GWF is a consultant for Ellodi, Allakos, Celgene, Lucid, Nexstone, Phathom, Regeneron, Bristol Myers Squibb, Upstream Bio, and Shire; has served on a data and safety monitoring board for Revolo; has a leadership role in the International Society for Diseases of the Esophagus; and has equity in Bristol Myers Squibb. SKG has received research support from Allakos, Ellodi, and AstraZeneca; receives royalties from UpToDate; is a consultant for Ellodi, Bristol Myers Squibb, QOL Medical, Takeda, and Viaskin; has received payment from Medscape and PeerView Institute for Medical Education; has served on a data and safety monitoring board for Bristol Myers Squibb; and has a leadership role in the Association of Pediatric Gastroenterology and Nutrition Nurses, American Gastroenterological Association, and Journal of Pediatric Gastroenterology and Nutrition. JL has received research funding AstraZeneca, Allakos, Takeda, Provention Bio, Ellodi, Arena Pharmaceuticals, GI Health Foundation, Ellodi, ALK Abelló, Revolo Biotherapeutics, Bristol Myers Squibb, Regeneron, Phathom Pharmaceuticals; has received consulting fees from Guidepoint, Takeda, Third Bridge, Boston Consulting Group, AbbVie, Sanofi, Huron Consulting Services, Ribon Therapeutics, Tegus, Slingshot, Cowen, and AstraZeneca; has received speaker payments from Regeneron, Sanofi, AGA Carney, AGA Tufts, and Maine Medical Center; has received payment for expert testimony for Devine, Millimet and Branch Professional Education; and has a leadership role with Kwong Kow Chinese School. IH has received consulting fees from Ellodi, AstraZeneca, Arena, Allakos, Calyx (formerly Parexel), Celgene, Celldex, Regeneron, Esocap, Gossamer Bio, Lilly, Phathom, Sanofi, and Shire; has received research funding Meritage, Ellodi, Celgene, Regeneron-Sanofi, and Shire; and participated in a speaker bureau for Regeneron and Sanofi. LJM has received honoraria from Akron's Children's Hospital and is co-inventor on a patent for Cysteamine. VAM has received consulting fees from Shire, Allakos, Regeneron, and Sanofi; and has received research funding and support from Meritage and Shire. KAP has received research support from Allakos, Ellodi, AstraZeneca, Chobani, Regeneron-Sanofi, and Revolo; is a consultant for AGA, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Invea, Lucid, Nexstone, WebMD, Peerview, Regeneron, Revolo, and Takeda; has received speaker payments from AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; has served on a data and safety monitoring board for Alladapt; and has a patent and stock options with Nexeos Bio. JMS is a consultant for Regeneron, Sanofi, DBV Technology, Ready Set Food, and Kaleo; has received research support from Regeneron-Sanofi, Food Allergy Research and Education, and Novartis; and has received royalties from UpToDate. GTF is Chief Medical Officer of EnteroTrack; and is a consultant for Shire. MER is a consultant for AstraZeneca, Bristol Myers Squibb, Regeneron-Sanofi, Revolo Biotherapeutics, Celldex, Nexstone One, and Guidepoint; has received research support from AstraZeneca, Regeneron-Sanofi, GlaxoSmithKline, the CURED Foundation, Food Allergy Fund, and a US–Israel Binational Grant (number 2019016); has equity interest in PulmOne Therapeutics, Spoon Guru, ClostraBio, Serpin Pharm, Celldex, Nextstone One, and Allakos; receives royalties from Ception Therapeutics (for reslizumab), Mapi Research Trust (for the Pediatric Eosinophilic Esophagitis Symptom Score version 2) and UpToDate; has received equipment from Phadia; has a leadership role in the International Eosinophil Society; has received payment for expert testimony from Tucker Ellis; and is an inventor on a patent (US patent 9,345,763) owned by Cincinnati Children's Hospital Medical Center. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls., Methods: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, 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 polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons., Results: One hundred thirty-nine 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 among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls., Conclusions: 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., Competing Interests: G.T.F. Chief Medical Officer, EnteroTrack, received research funding from NIH, Arena, and Holoclara. S.S.A. is co-inventor, oral viscous budesonide, Takeda license, UCSD patent. She received consulting fees from Regeneron/Sanofi, AstraZeneca, and Bristol Meyers Squibb. She received funding from NIH/NIAID/NIDDK. M.C. received consultant fees from Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, Bristol Myers Squibb, and Phathom. She received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, and Danone. S.K.G. received consultant fees from Abbott, Adare, Celgene, Gossamer Bio, QOL, Takeda, MedScape, ViaSkin, and UpToDate. He received research support from Allakos, Ellodi, and AstraZeneca. V.A.M. received consultant fees from Takeda, Allakos, and Sanofi. He is on the Adjudication Committee of Alladapt. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Eosinophilic gastritis and eosinophilic duodenitis (EoG/EoD) are often misdiagnosed as functional gastrointestinal (GI) disorders. Consequently, patients with GI symptoms of EoG/EoD may not undergo the necessary steps for diagnosis. We studied gastroenterologists' evaluations of patients with chronic, unexplained, moderate-to-severe GI symptoms that were unresponsive to over-the-counter medications., Methods: We performed a cross-sectional online survey of 202 board-certified gastroenterologists at office-based practices, community hospitals, or academic institutions. Respondents had been in active clinical practice for 3-35 years post-residency training, spent most of their time on direct patient care, managed ≥1 patient with irritable bowel syndrome and/or functional dyspepsia, and performed ≥1 endoscopy per month. Responses were analyzed to identify barriers to EoG/EoD diagnosis and management., Results: Respondents managed a mean of 1880 patients per year; the most common diagnoses were functional dyspepsia (36%) and gastroesophageal reflux disease (19%). Mean proportions of patients who underwent upper endoscopy ranged from 42% to 84%. Biopsies were collected from >90% of patients with visible endoscopic mucosal abnormalities vs 42%-72% of patients with normal-appearing mucosae. Approximately 20% of respondents collected only 1-2 biopsies from each site of the GI tract. Only 30% routinely requested pathologists to count eosinophils, and nearly 40% had no histologic threshold for EoG/EoD diagnosis., Conclusion: Gastroenterologists vary in their evaluation of patients with chronic, unexplained moderate-to-severe GI symptoms. Limited gastric and duodenal biopsy collection, particularly from normal-appearing mucosae, and failure to request tissue eosinophil counts might contribute to underdiagnosis of EoG/EoD. Availability and awareness of EoG/EoD diagnostic guidelines should improve detection in clinical practice., (© 2022 Published by Elsevier, Inc on behalf of the AGA Institute.)

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature., Methods: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement., Results: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When &gt;2 GI tract areas are involved, the name should reflect all of the involved areas., Conclusions: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science., (Copyright © 2022. Published by Elsevier Inc.)

Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science-based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL-13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Objective: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants., Design: Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm 2 (<15/hpf) in esophageal biopsies and absence of gastro-esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)-histological, and molecular features were determined and compared with EoE, GERD, and healthy controls., Results: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE-like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non-specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed-in contrast to EoE-no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE-typical Th2-response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE-like (characterized by eotaxin-3 expression), non-specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression)., Conclusion: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)