Safety of EUS latex balloon use in patients with a latex allergy.

BACKGROUND AND AIMS: Balloons are used in EUS to improve visualization. However, data on the safety of latex balloons in patients with latex allergies are limited, and nonlatex alternatives can be costly. We investigated the safety of latex balloon use during EUS. METHODS: A retrospective review was conducted at a tertiary center between 2019 and 2022. Patients with reported latex allergies who underwent linear EUS were included. Baseline demographics, EUS characteristics, and adverse events were collected. The primary outcome was the rate of adverse events. RESULTS: Eighty-seven procedures were performed on 57 unique patients (mean age, 65.3 ± 14.5 years). Latex balloons were used in 59 procedures (67.8%), with only 8 procedures (13.6%) using prophylactic medications. No adverse events occurred during or after procedures, regardless of medication use or history of anaphylaxis. CONCLUSIONS: The use of EUS latex balloons in patients with a latex allergy was associated with no adverse events.

H influenzae LPS colocalization with Toll-like receptor 4 in eosinophilic esophagitis.

Background: Patients with eosinophilic esophagitis (EoE) have a unique esophageal microbiome with increased presence of Haemophilus influenzae, but its role in the disease is unclear. Objective: Microbiome-derived bacterial LPS activation of Toll-like receptors (TLR) is a potential mechanism for inducing inflammation in other chronic inflammatory diseases, but it has not been studied in EoE. Our aim was therefore to study microbiome-derived bacterial LPS activation of TLRs in EoE. Methods: We studied 10 patients with active EoE, 9 patients with inactive EoE, and 10 control patients. Esophageal biopsy samples from the controls, patients with active EoE (>15 eosinophils/hpf), and patients with inactive EoE were immunostained for the presence of H influenzae LPS, presence of TLR4, and colocalization of LPS and TLR4. Staining intensity was measured by using confocal laser microscopy and scored on a scale from 0 to 3 as the average score assigned by 2 blinded observers. Results: H influenzae LPS was detected by positive staining in 20 of the 29 patients (69.0%), including 9 of the 10 patients with active EoE (90.0%), 8 of the 9 patients with inactive EoE (89.9%), and 3 of the 10 controls (30%); its level was greater in the patients with active EoE than in the controls (P = .063). TLR4 was detected by positive staining in 19 of the 29 patients (65.5%), including 9 of the 10 patients with active EoE (90.0%), 4 of the 9 patients with inactive EoE (44.4%), and 6 of the 10 controls (60.0%); its level was higher in the patients with active EoE than in those with inactive EoE (P = .096). The result of testing for colocalization of LPS and TLR4 was positive in 8 of 10 patients with active EoE (80.0%), 1 of 9 patients with inactive EoE (11.1%), and 1 of 10 control patients (10.0%), with greater colocalization of H influenzae LPS and TLR4 staining density in the samples from patients with active EoE than in the controls or the patients with inactive EoE (P = .009 and P = .018, respectively). Conclusion: Esophageal microbiome-rich H influenzae LPS colocalizes to TLR4 in active EoE. These data lend further support to a role for the esophageal microbiome in modulating the activity of EoE.

Rapid Rise of Pediatric Telehealth During COVID-19 in a Large Multispecialty Health System.

Background: Before the COVID-19 pandemic, telemedicine use for outpatient pediatric specialty care was low. Stay-at-home orders (SHO) prompted rapid upscaling of telemedicine capabilities and upskilling of providers. This study compares telemedicine usage before and after the SHO and analyzes how a Children's Center addressed challenges associated with a rapid rise in telemedicine. Methods: Data on outpatient visits across 14 specialty divisions were abstracted from the institutional electronic medical record. The 12-week study period (March 9, 2020-May 29, 2020) spanned three epochs: pre-SHO; post-SHO; reopening to in-person visits. Changes in in-person visits, video visits, and completed, cancelled, and no-show appointments were compared between three epochs. Results: A total of 4,914 outpatient pediatric specialty visits were completed, including 67% (3,296/4,914) in-person and 33% (1,618/4,914) through video. During the first two epochs encompassing the SHO, video visits increased by 4,750%. During the third epoch when the SHO was lifted, video visits decreased by 66%, with 19.4% of visits conducted through video in week 12. Overall, for outpatient video appointments, 82.8% (1,618/1,954) were completed, 9.1% (178/1,954) were cancelled, and 8.1% (158/1,954) were no-shows. The percentage of completed and no-show appointments did not differ between epochs. However, the cancellation rate decreased significantly from Epochs 1 to 3 (p = 0.008). Conclusion: A SHO was associated with a large increase in pediatric specialty video visits. Post-SHO, the percentage of pediatric specialty visits conducted through video decreased but remained higher than before the SHO. Frequent, content-rich communications, self-directed tutorials, and individualized coaching may facilitate successful increases in telemedicine use.

Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis.

BACKGROUND: The Th2 allergic pathway in eosinophilic oesophagitis (EoE) responds to food antigen exposure. AIM: To compare the presence and temporal pattern of food antigen penetration in oesophageal mucosa in active and inactive EoE and controls METHODS: Thirty-two patients with EoE (20 active) and 10 controls were asked to eliminate all wheat and/or dairy 12, 24, 48, 72 or 96 hours before endoscopy. Immunostaining on endoscopic biopsies was performed for gliadin, casein and whey. RESULTS: Gluten, casein and whey were detected by positive staining in 17/32 (53.1%), 21/32 (65.6%), and 30/32 (92.0%) of patients, respectively. In active vs inactive EoE, 70.0% vs 25.0% (P < 0.05), 80.0% vs 41.5%, and 90.0% vs 90.9% patients had detectable gliadin, casein and whey, respectively. Casein and whey (20.0% and 100%, respectively) but not gliadin, were present in controls. The gliadin staining density was greater in active compared to inactive disease at ≤ 24 vs >24 hours after exposure (P = 0.05) but no differences were detected when comparing active and inactive patients for casein and whey. There was greater staining density for whey than casein for all patients at ≤24 hours (mean 2.14 ± 0.91 and 1.07 ± 1.33, P = 0.02). In active EoE, IgG4 was present in 14/20 compared to one inactive patient. CONCLUSION: The oesophageal epithelium is selectively permeable and has relatively long dwell times for food antigens known to trigger EoE. The precise mechanism of antigen-specific mucosal entry and the factors that determine the induction or effector trigger of the Th2 pathway activation merit further study.

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management.

Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

Mast Cell Mediators of Significance in Clinical Practice in Mastocytosis.

Mast cells leave evidence, a "fingerprint," of their participation in acute and chronic clinical events. That fingerprint is an elevation, either chronic or acute, in levels of their secreted mediators or their metabolites. Of these, only serum tryptase is currently one of the diagnostic criteria for systemic mastocytosis or mast cell activation. Combinations of easily obtained and quantified urinary mast cell mediator metabolite levels correlate well with bone marrow findings of systemic mastocytosis. By inhibiting synthesis of or blockading receptors to the elevated mast cell mediator, relief of clinical symptoms can often be achieved.

Colectomy in refractory Crohn's colitis improves nutrition and reduces steroid use.

BACKGROUND: Pediatric patients with severe refractory Crohn's colitis (CC) may require total colectomy (TC) or diverting loop ileostomy (DLI). Our understanding of outcomes (postoperative complications, nutrition and restoration of intestinal continuity) is currently limited. METHODS: Pediatric patients with severe CC who underwent TC or DLI were identified. Demographics, pre and postoperative anthropometric and biochemical data, surgical complications and medication requirements were recorded. RESULTS: Twenty-seven patients (TC=22, DLI=5) with a median age of 15.0years (range 3-18) were identified, 64% male with a median follow-up of 45months (range 3-120). Mean weight and BMI improved for TC patients by 1year postoperatively - weight z-score from -1.08 to -0.54 (p=0.02), BMI z-score from -0.83 to -0.38 (p=0.04), with a non-significant height change from - 0.79 to -0.65 (p=0.07). Mean hemoglobin and albumin both also improved - 9.88g/dl to 11.76g/dl (p=0.003) and 3.44g/dl to 4.03g/dl (p=0.004) respectively. These measures did not significantly improve after DLI. Most TC patients (59%) had attempted restoration of intestinal continuity with 45% in continuity at end of follow-up. One DLI patient underwent ileostomy takedown but subsequently needed re-diversion. CONCLUSIONS: In severe CC, TC offers an opportunity to improve nutrition and growth, with a reasonable likelihood of restoring intestinal continuity. LEVEL OF EVIDENCE: Level IV - Case series.

Continuous 48-Hour Wireless Esophageal pH Monitoring in Children: Comparison Between Days 1 and 2.

AIM: Comparison of days 1 and 2 to each other and to the total recording of 48 hours in continuous 48-hour wireless esophageal pH monitoring in children. METHODS: A retrospective study of 105 patients who underwent 48-hour pH monitoring (Bravo) studies between January 1992 and June 2010 was performed. Reflux variables were compared between days 1 and 2. RESULTS: A total of 58 (55.2%) patients were men. The number of reflux episodes, number of long reflux >5 minutes, duration of the longest reflux (minutes), time pH <4 (minutes), fraction time pH <4 supine (%), fraction time pH <4 upright (%), reflux index, and DeMeester score did not differ between days 1 and 2. CONCLUSIONS: No effect of anesthesia was observed on the gastroesophageal reflux parameters on children.

Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis.

BACKGROUND & AIMS: Management of eosinophilic esophagitis (EoE) requires repeated endoscopic collection of mucosal samples to assess disease activity and response to therapy. An easier and less expensive means of monitoring of EoE is required. We compared the accuracy, safety, and tolerability of sample collection via Cytosponge (an ingestible gelatin capsule comprising compressed mesh attached to a string) with those of endoscopy for assessment of EoE. METHODS: Esophageal tissues were collected from 20 patients with EoE (all with dysphagia, 15 with stricture, 13 with active EoE) via Cytosponge and then by endoscopy. Number of eosinophils/high-power field and levels of eosinophil-derived neurotoxin were determined; hematoxylin-eosin staining was performed. We compared the adequacy, diagnostic accuracy, safety, and patient preference for sample collection via Cytosponge vs endoscopy procedures. RESULTS: All 20 samples collected by Cytosponge were adequate for analysis. By using a cutoff value of 15 eosinophils/high power field, analysis of samples collected by Cytosponge identified 11 of the 13 individuals with active EoE (83%); additional features such as abscesses were also identified. Numbers of eosinophils in samples collected by Cytosponge correlated with those in samples collected by endoscopy (r = 0.50, P = .025). Analysis of tissues collected by Cytosponge identified 4 of the 7 patients without active EoE (57% specificity), as well as 3 cases of active EoE not identified by analysis of endoscopy samples. Including information on level of eosinophil-derived neurotoxin did not increase the accuracy of diagnosis. No complications occurred during the Cytosponge procedure, which was preferred by all patients, compared with endoscopy. CONCLUSIONS: In a feasibility study, the Cytosponge is a safe and well-tolerated method for collecting near mucosal specimens. Analysis of numbers of eosinophils/high-power field identified patients with active EoE with 83% sensitivity. Larger studies are needed to establish the efficacy and safety of this method of esophageal tissue collection. ClinicalTrials.gov number: NCT01585103.

Mast cell activation syndrome: improved identification by combined determinations of serum tryptase and 24-hour urine 11ß-prostaglandin2α.

BACKGROUND: Mast cell activation syndrome (MCAS) describes patients with episodes of mast cell mediator release, with negative bone marrow biopsy results, and the failure to meet the criteria for systemic mastocytosis. OBJECTIVE: Identify elevation of mast cell mediators of patients with MCAS. METHODS: We performed a retrospective study of 25 patients with MCAS who were evaluated at Mayo Clinic from 2006 to 2012. Patients were reviewed for MCAS symptoms and mast cell mediators, including serum tryptase and 24-hour urine N-methyl histamine (N-MH) and 11ß-prostaglandin-F2α (11ß-PGF2α). The study was approved by the institutional review board. RESULTS: Urinary 11ß-PGF2α was the most frequently elevated product in MCAS of our 25-patient cohort. Flushing and pruritus had the greatest correlation with elevation of 24-hour urine 11ß-PGF2α value at baseline. The serum tryptase level was elevated in 10 patients, whereas the N-MH level was elevated with 2 patients. Eight of 9 patients with MCAS and with elevated 24-hour urine 11ß-PGF2α who underwent aspirin therapy and follow-up urinary studies had normalization of this mediator (1 patient did not have a follow-up urine study). Six of these 9 patients with MCAS who underwent aspirin therapy had symptomatic improvement. CONCLUSION: We recommend measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels of patients with symptoms suggestive of MCAS. Measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels can help avoid misdiagnosis and overinterpretation of MCAS symptoms in clinical practice. Given that an elevation of 24-hour urine N-MH level was found only in 2 patients, measurement of this mediator may be less helpful in diagnosing MCAS. We recommend aspirin therapy for patients with MCAS and with elevated 24-hour urine 11ß-PGF2α levels.

Reducing and managing systemic reactions to immunotherapy.

PURPOSE OF REVIEW: To identify and discuss recent articles pertaining to the reduction and management of systemic reactions to allergen immunotherapy (AIT). RECENT FINDINGS: Fatal reactions to AIT may be declining. Screening asthma patients before AIT and dose adjustment during pollen season may contribute to lower systemic reaction rates. Cluster build-up protocols with multiallergen subcutaneous immunotherapy (SCIT) may lead to an increased risk of systemic reactions compared with cluster build-up protocols with single-allergen SCIT. Sublingual immunotherapy (SLIT) studies confirm the low rates of systemic reactions using this method, including for rapid build-up schedules. Studies of newer forms of AIT (intralymphatic, epicutaneous, recombinant allergens) have too few patients to form confident systemic reaction risk estimates. High-grade delayed systemic reactions to AIT may be less frequent than previously reported. SUMMARY: Recent studies increase confidence in risk estimates for systemic reactions to AIT, suggest useful strategies to predict systemic reactions to AIT, and offer strategies to prevent systemic reactions.

Matrix metalloproteinase-9 regulates MUC-2 expression through its effect on goblet cell differentiation.

BACKGROUND & AIMS: We recently demonstrated that epithelial-derived matrix metalloproteinase (MMP) 9 up-regulated during inflammatory bowel disease is a critical mediator of tissue damage during colitis. MMP-9 null mice (MMP-9(-/-)) develop dramatically reduced inflammatory response to luminally administered colitic agents in the face of intact systemic immune response and inflammatory cell recruitment, suggesting protected epithelial barrier in these mice. In this study, we sought to address the role and mechanism by which MMP-9 influences barrier protective function. METHODS: Wild-type and MMP-9(-/-) mice were used for in vivo studies, and the goblet cell line HT29-cl.16E and the enterocyte cell line Caco2-BBE were used for in vitro studies. RESULTS: Compared with wild-type mice, MMP-9(-/-) mice had an increased number of goblet cells and MUC-2 expression. In addition, KLF-4 and Elf-3, transcription factors involved in terminal differentiation of goblet cells were up-regulated, whereas notch intracellular domain (NICD; activated Notch-1) was down-regulated in MMP-9(-/-) mice. These findings suggest altered epithelial cell differentiation in MMP-9(-/-) mice. Temporal expression of MMP-9 inversely correlated with MUC-2 expression during maturation of goblet cells. MMP-9 over expression inhibited goblet cell differentiation in vitro. Conversely, MMP-9 gene silencing in Caco2-BBE cells resulted in a change in their phenotype toward goblet cells. Finally, MMP-9 over expression or silencing in goblet cells increased or decreased Salmonella typhimurium adherence, respectively. CONCLUSIONS: MMP-9 regulates goblet cell differentiation in colon. The effect of MMP-9 on goblet cells could contribute to alteration in mucosal defense leading to inflammation. Together, our data uncover a novel function of MMP-9 in intestinal epithelial cells.

Wells' syndrome associated with ulcerative colitis: a case report and literature review.

Wells' syndrome, also termed eosinophilic cellulitis, is a dermatologic condition of unknown etiology that occurs as recurrent patches or plaques mimicking infectious cellulitis. Histopathology reveals an eosinophilic infiltrate and characteristic flame figures. Previous reports have associated this syndrome with parasitic infections, arthropod bites, pharmacologic agents, surgery, and hematologic disorders. We present a case report of a patient with Wells' syndrome associated with newly diagnosed ulcerative colitis. The dermatosis erupted concurrently with flares of ulcerative colitis. Furthermore, treatment of the ulcerative colitis led to resolution of the skin lesions. To our knowledge this describes the first association between inflammatory bowel disease and Wells' syndrome and argues for a distinct relationship between the two.

Matrix metalloproteinases in inflammatory bowel disease: boon or a bane?

Matrix metalloproteinases (MMPs) are a family of Zn(2+)-dependent extracellular matrix (ECM) degrading endopeptidases that share common functional domains, activation mechanisms, and collectively have the capacity to degrade all types of ECM proteins. In addition to playing a central role in ECM turnover, MMPs proteolytically activate or degrade a variety of nonmatrix substrates including chemokines, cytokines, growth factors, and junctional proteins. Thus, they are increasingly recognized as critical players in inflammatory response. Indeed, accumulating data from several studies indicate that they are the predominant proteases involved in the pathogenesis of inflammatory bowel disease (IBD) via their influence on the function and migration of inflammatory cells, mucosal ulceration, as well as matrix deposition and degradation. Some MMPs are constitutively expressed and play a protective role in IBD through their effect on cellular homeostasis, while others are induced during inflammation-mediated tissue damage. This article focuses on the role of the various MMPs in IBD, discussing their physiologic and pathogenetic role in the context of intestinal defense, mucosal inflammatory response, and immune cell-epithelial interaction.

Selective ablation of matrix metalloproteinase-2 exacerbates experimental colitis: contrasting role of gelatinases in the pathogenesis of colitis.

The matrix metalloproteinases (MMPs), MMP-2 and MMP-9, share structural and substrate similarities and are up-regulated during human as well as animal models of inflammatory bowel disease. We recently demonstrated that epithelial-derived MMP-9 is an important mediator of inflammation and tissue damage in colitis. In this study, we examined the role of MMP-2 in acute colitis. Colitis was induced using two models, administration of dextran sodium sulfate (DSS) and Salmonella enterica subsp. serovar Typhimurium (S.T.). Bone marrow chimeras were performed using bone marrow cells from wild-type (WT) and MMP-2(-/-) mice. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, and histology. MMP-2 protein expression and activity were up-regulated in WT mice treated with DSS or S.T. MMP-2(-/-) mice were highly susceptible to the development of colitis induced by DSS (or S.T.) compared with WT. During inflammation, MMP-2 expression was increased in epithelial cells as well as in the infiltrating immune cells. Bone marrow chimera demonstrated that mucosa-derived MMP-2 was required for its protective effects toward colitis. Furthermore, we demonstrate that severe colitis in MMP-2(-/-) is not due to a compensatory increase in MMP-9. Finally, we show that MMP-2 regulates epithelial barrier function. In contrast to MMP-9, mucosa-derived MMP-2 may be a critical host factor that is involved in the prevention or cessation of the host response to luminal pathogens or toxins, an important aspect of healing and tissue resolution. Together, our data suggest that a critical balance between the two gelatinases determines the outcome of inflammatory response during acute colitis.