Emotional Journey of Patients with Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic and progressive disease associated with dysphagia and eosinophilic infiltration of the esophageal mucosa. EoE can have a negative impact on a patient's quality of life (QoL); however, there is very limited data reflecting the emotional journey of patients with EoE or their perceived unmet needs. The aim of this study was to determine the emotional impact of EoE on patients at each stage of the patient journey. METHODS: In this cross-sectional and qualitative research study, adult patients with EoE from eight different countries provided their experiences and feelings across each stage of the patient journey through one-on-one semi-structured interviews. RESULTS: Twenty-one patients with EoE were enrolled in the study. The results of the one-on-one interviews showed that patients living with EoE go through an exhausting emotional experience during the different stages of the patient journey. In the pre-seeking-care stage, patients feel confused, afraid, frustrated, anxious, lonely, and misunderstood. During the diagnostic process, patients feel highly frustrated and angry because of the long and burdensome process. When EoE is finally diagnosed, patients feel liberated and relieved. When treatment is initiated, patients feel relief and enthusiasm, and, once the treatment starts to be effective and during the monitoring stage, they feel happier, less stressed, more confident, more relaxed, less fearful, and more in control owing to the improvement of their symptoms. CONCLUSIONS: This study pays attention to the different stages of the journey of patients with EoE. There is a lack of awareness by both physicians and patients that negatively affects every stage of the patient journey, but especially the initial phases of pre seeking care and diagnosis. We intend for this article to represent an opportunity to increase EoE awareness and to show the importance of considering the emotional impact on a patient with EoE's journey.

Investigating immune profile by CyTOF in individuals with long-standing type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Eosinophils are found in pancreatic tissue from individuals with T1D. Eosinophilic suppression of T cells is dependent of the protein galectin-10. Little is known when it comes to the role of eosinophil granulocytes in type 1 diabetes. Here we show that individuals with long-standing T1D had lower levels of galectin-10hi eosinophils and a subgroup of galectin-10hi eosinophils were entirely absent in all T1D patients. In addition, 7% immature eosinophils were present in the circulation of T1D patients whereas 0.8% in healthy individuals. Furthermore, higher levels of CD4+CD8+ T cells and Th17 cells were observed in patients with T1D. Blood samples from 12 adult individuals with long-standing T1D and 12 healthy individuals were compared using cytometry by time-of-flight. Lower levels of galectin-10hi eosinophils, which are potent T cell suppressors, in individuals with T1D could indicate that activated T cells are enabled to unrestrictedly kill the insulin producing beta cells. This is the first study showing absence of galectin-10hi eosinophilic subgroup in individuals with T1D compared with healthy controls. This study is a first important step toward unraveling the role of the eosinophils in patients with T1D.

Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis.

Eosinophilic esophagitis is a T-cell-driven allergic condition hallmarked by eosinophil infiltration of the esophagus. Eosinophils exposed to proliferating T cells release galectin-10 and have T-cell suppressive function in vitro. The aims of this study were to evaluate if eosinophils co-localize with T cells and release galectin-10 in the esophagus of patients with eosinophilic esophagitis. Esophageal biopsies from 20 patients with eosinophilic esophagitis were stained for major basic protein, galectin-10, CD4, CD8, CD16, and CD81 and analyzed by immunofluorescence confocal microscopy before and after topical corticosteroid treatment. CD4+ T-cell numbers decreased in the esophageal mucosa of responders to treatment but not in the non-responders. Suppressive (CD16+) eosinophils were present in the esophageal mucosa of patients with active disease and decreased after successful treatment. Unexpectedly, eosinophils and T cells were not in direct contact with each other. Instead, the esophageal eosinophils released large amounts of galectin-10-containing extracellular vesicles and featured cytoplasmic projections that contained galectin-10, both of which disappeared from the esophagus of the responders but remained in the non-responders. To conclude, the presence of CD16+ eosinophils together with the massive release of galectin-10-containing extracellular vesicles in the esophageal mucosa might indicate that eosinophils exert T-cell suppression in eosinophilic esophagitis.

TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial.

BACKGROUND: Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy. METHODS: SARS-CoV-2-infected patients within the Region Västra Götaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (≤ 7 days after intubation) or late tracheotomy (≥ 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups. RESULTS: One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference: - 1.5 days (95% CI - 5.7 to 2.8); p = 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: - 8.0 days (95% CI - 13.8 to - 2.27); p = 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman's correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events. CONCLUSIONS: The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out. Trial registration NCT04412356 , registered 05/24/2020.

Validation of the Swedish Watson Dysphagia Scale for adult patients with eosinophilic esophagitis.

BACKGROUND: The Swedish Watson Dysphagia Scale (S-WDS) has been used to assess dysphagia in patients with eosinophilic esophagitis (EoE) but has not been validated for this patient group. The aim of this study was to validate the S-WDS for adult patients with EoE. METHODS: Ninety-seven Swedish adult patients with EoE and 97 controls without dysphagia filled out the S-WDS, the Swedish Eosinophilic Esophagitis Activity Index (S-EEsAI) and a set of supplementary questions. The reliability of the S-WDS was evaluated using Cronbach's alpha, Pearson correlation of items and total score, and test-retest analysis (n = 29). Validity was investigated using Spearman correlations of the S-WDS items, S-EEsAI domains and a self-assessment score, and by investigating floor and ceiling effects. RESULTS: The Cronbach's alpha of the S-WDS was 0.77 and all items demonstrated moderate to strong correlation to the S-WDS score (r = 0.40-0.81) indicative of sufficient reliability of the instrument. In addition, the test-retest results reflected excellent reliability with an intraclass correlation coefficient of 0.85 for the S-WDS score. Adequate validity of the instrument was demonstrated, the S-WDS score correlated moderately with the self-assessment score and with 4/6 S-EEsAI domains, and strongly with the remaining two domains. Floor effects were more common for liquids and soft-textured foods and ceiling effects increased with increasing food consistency. The S-WDS scores of the patient group were significantly different from those of the nondysphagia control group (P < 0.001). CONCLUSION: The S-WDS instrument is an appropriate and valid instrument for assessment of dysphagia in patients with EoE.

Patient-Reported Dysphagia in Adults with Eosinophilic Esophagitis: Translation and Validation of the Swedish Eosinophilic Esophagitis Activity Index.

The lack of a Swedish patient-reported outcome instrument for eosinophilic esophagitis (EoE) has limited the assessment of the disease. The aims of the study were to translate and validate the Eosinophilic Esophagitis Activity Index (EEsAI) to Swedish and to assess the symptom severity of patients with EoE compared to a nondysphagia control group. The EEsAI was translated and adapted to a Swedish cultural context (S-EEsAI) based on international guidelines. The S-EEsAI was validated using adult Swedish patients with EoE (n = 97) and an age- and sex-matched nondysphagia control group (n = 97). All participants completed the S-EEsAI, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18), and supplementary questions regarding feasibility and demographics. Reliability and validity of the S-EEsAI were evaluated by Cronbach's alpha and Spearman correlation coefficients between the domains of the S-EEsAI and the EORTC QLQ-OES18. A test-retest analysis of 29 patients was evaluated through intraclass correlation coefficients. The S-EEsAI had sufficient reliability with Cronbach's alpha values of 0.83 and 0.85 for the "visual dysphagia question" and the "avoidance, modification and slow eating score" domains, respectively. The test-retest reliability was sufficient, with good to excellent intraclass correlation coefficients (0.60-0.89). The S-EEsAI domains showed moderate correlation to 6/10 EORTC QLQ-OES18 domains, indicating adequate validity. The patient S-EEsAI results differed significantly from those of the nondysphagia controls (p < 0.001). The S-EEsAI appears to be a valid and reliable instrument for monitoring adult patients with EoE in Sweden.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

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

Topically applied mometasone furoate improves dysphagia in adult eosinophilic esophagitis - results from a double-blind, randomized, placebo-controlled trial.

OBJECTIVES: Topical corticosteroids are considered a cornerstone in the treatment of patients with eosinophilic esophagitis. The aim of this study was to evaluate the benefit of using mometasone furoate spray versus placebo on dysphagia and health-related quality of life in these patients. MATERIAL AND METHODS: Consecutive, newly diagnosed adult patients with eosinophilic esophagitis were randomized and treated with either 200 micrograms of orally administered topical mometasone furoate or placebo 4 times daily for 8 weeks. Symptoms and quality of life were evaluated using questionnaires including the Watson Dysphagia Scale, the European Organization for Research and Treatment of Cancer Quality of Life-Oesophageal Module 18 and the Short Form-36 before and after treatment. RESULTS: In the intention-to-treat analysis (n = 36) the Watson Dysphagia Scale score after mometasone treatment was reduced by 6.5 (median, p < .01) compared with 0 (median, ns) in the placebo group. The benefit of mometasone over placebo was significant (p < .05). In the per-protocol analysis (n = 33) the Watson Dysphagia Scale score was reduced by 5 (median, p = .01) after mometasone treatment compared with 0 (median, ns) in the placebo group. The advantage of mometasone over the placebo was significant (p < .05). The benefit of using mometasoneas evaluated by the two quality of life questionnaires was, however, insignificant. CONCLUSIONS: Our finding suggests that in adult patients with eosinophilic esophagitis, topical mometasone furoate exerts a beneficial effect compared with placebo regarding the main symptom, i.e., dysphagia. A corresponding benefit could not be verified regarding the various quality of life measurements. CLINICAL TRIAL REGISTRATION: Mometasone-furoate for Treatment of Eosinophilic Esophagitis - a Randomized Placebo Controlled Study ClinicalTrials.gov Identifier (NCT02113267).

Patient-Reported Outcomes and Blood-Based Parameters Identify Response to Treatment in Eosinophilic Esophagitis.

BACKGROUND: Noninvasive methods to assess treatment response in eosinophilic esophagitis are needed. AIMS: Our aim was to determine whether a blood-based biomarker panel centered on immune parameters could identify histologic response to treatment in eosinophilic esophagitis patients. METHODS: A pilot study involving adult patients with active eosinophilic esophagitis recruited at two Ear, Nose, Throat clinics in Sweden was designed. The patients (n = 20) donated blood and esophageal biopsies and filled in three questionnaires before and after a 2-month course of topical corticosteroids. Blood samples were analyzed for absolute levels of granulocytes and T cells and the fractions of eosinophils expressing 10 different surface markers by flow cytometry. All data were analyzed by multivariate methods of pattern recognition. RESULTS: Multivariate modeling revealed that a combination of 13 immune parameters and 10 patient-reported outcome scores were required to create a model capable of separating responders (n = 15) from non-responders (n = 5). Questions regarding symptoms of esophageal dysfunction and capacity to eat certain foods from two of the questionnaires were discriminatory in the multivariate model, as were absolute counts of T cells, eosinophils, and eosinophil expression of activation markers and cell adhesion molecules. CONCLUSIONS: A combination of blood-based immune parameters and directed questions may prove helpful to monitor response to treatment, perhaps reducing the need for repeat endoscopies in eosinophilic esophagitis patients in the future.

Eosinophilic esophagitis (EoE); a disease that must not be neglected - implications of esophageal rupture and its management.

BACKGROUND: The prevalence of Eosinophilic esophagitis (EoE) is increasing, a severe complication of EoE is spontaneous perforation of the oesophagus. It is of great importance to be aware of this risk and handle this severe complication carefully. CASE PRESENTATION: A middle-age man with EoE since 2004, had a total esophageal bolus obstruction while eating lunch at the local hospital. Drinking water, in an attempt to release it, led to a total intramural ruptur of the esophageal wall. A CT scan detected the injury and a covered esophageal stent was inserted within 2 h from the injury. Despite the immediate hospital care, he developed mediastinitis, were in need of a laparascopy and intensive care. After 8 weeks the stent was removed and the esophagus was considered healed. Biopsies from the esophagus showed an eosinophilic inflammation (65 eosinophils/HPF). Twelve weeks from the injury he was essentially back in his normal state and was discharged from the hospital. He was placed on a 6 weeks course of topical treatment with budesonide, which needed to be extended due to inadequate remission. Remission was achieved after 12 weeks of treatment. CONCLUSION: An effective topical steroid treatment in EoE patients is important. EoE patients are in risk of oesophageal perforation, if so, management may be conservative but mediastinal drainage is important if significant extravasation occurs and should be instituted from the start.

Retrospective chart review: seasonal variation in incidence of bolus impaction is maintained and statistically significant in subgroups with atopy and eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition with eosinophilic infiltration of the esophageal mucosa. The most prominent symptom is dysphagia, which may result in esophageal bolus impaction in need of surgical extraction. To investigate whether an earlier reported seasonal variation in esophageal bolus impaction present only in a subgroup of patients with EoE and atopic disorders could be confirmed in this larger study. A single center retrospective chart review of patients who were diagnosed with esophageal bolus impaction between January 2004 and December 2017 was performed. Clinical, epidemiological and histologic data were collected. A total of 755 cases with esophageal bolus impaction were reviewed. A significantly higher occurrence of soft bolus impaction in summer and fall was shown in cases with confirmed EoE and in cases with atopy but not in the nonatopic group or in the group with a negative biopsy result. EoE was found in 48% of biopsied patients. A significant seasonal variation in cases with esophageal bolus impaction and concomitant atopy and EoE is confirmed, but the study design does not allow a causative role of allergens to be established.

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults.

INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. RESULTS: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. CONCLUSION: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

Dysphagia and health-related quality of life in patients with eosinophilic esophagitis: a long-term follow-up.

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disease, with dysphagia as the main symptom. The aim of this study was to survey symptoms and health-related quality of life in adult patients with EoE at least 1 year after diagnosis and a 2-month course of topical corticosteroids. Forty-seven consecutive patients [79 % males, mean age 49 years (range 18-90 years)] were evaluated using three different questionnaires at three different occasions: the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18) and the Short Form-36 (SF-36). The median time from diagnosis to the long-term follow-up was 23 months (range 12-34 months). The WDS scores and the EORTC QLQ-OES18 Dysphagia and Eating scale scores were improved after 2 months of treatment (p = 0.00007, p = 0.01, p = 0.004, respectively), as were the long-term follow-up scores (p = 0.01, p = 0.03, p = 0.005, respectively), relative to the scores at diagnosis. In addition, the EORTC QLQ-OES18 Choking scores were improved after the steroid course (p = 0.003) but not after the long-term follow-up. No significant differences were detected with respect to the SF-36 scores. In summary, EoE seems to be associated with a substantial burden of symptoms that improve significantly after treatment. A partial remission persists more than 1 year after diagnosis and the discontinuation of medication. The WDS and the EORTC QLQ-OES18 appear to be sensitive instruments appropriate for surveillance in these patients.

Dysphagia and quality of life may improve with mometasone treatment in patients with eosinophilic esophagitis: a pilot study.

OBJECTIVE: The treatment of adult patients with eosinophilic esophagitis remains challenging. The aim was to assess dysphagia and health-related quality of life (HRQL) using validated scales and questionnaires before and after treatment with mometasone furoate. STUDY DESIGN: Case series with planned data collection. SETTING: University hospital and secondary referral hospital. SUBJECTS AND METHODS: Newly diagnosed patients with eosinophilic esophagitis were included and given 200 µg of orally administered topical mometasone furoate 4 times daily. Questionnaires incorporating the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life-Oesophageal Module 18 (EORTC QLQ-OES18), and the Short Form-36 (SF-36) were completed before the initiation of treatment and after 2 months of treatment. RESULTS: Thirty-one consecutive patients (23 men; mean age, 45 years; range, 18-89 years) completed the trial. At inclusion, the mean scores of the WDS, the EORTC QLQ-OES18 dysphagia scale, the eating scale and choking item, and the global health and social functioning dimensions of the SF-36 were 21.3, 20.4, 35.0, 38.6, 71.1, and 82.3, respectively. Posttreatment, these scores improved to 8.9 (P < .0001), 4.6 (P < .00001), 17.8 (P < .001), 16.0 (P < .01), 76.1 (P < .05), and 91.9 (P = .0001), respectively. Except for 1 case of oral candidiasis, no significant side effects were reported. CONCLUSION: The dysphagia and impaired HRQL found in untreated patients with eosinophilic esophagitis improved significantly after 2 months of mometasone furoate treatment. A randomized placebo-controlled trial is warranted to assess causality. The scales and questionnaires used are sensitive instruments appropriate for symptom surveillance in individuals with eosinophilic esophagitis.

The incidence of esophageal bolus impaction: is there a seasonal variation?

OBJECTIVES: Eosinophilic esophagitis is a disease associated with dysphagia and has a seasonal variation in incidence. The primary aim of this study was to search for a potential seasonal variation in the incidence of esophageal foreign bodies or food impaction. In addition, after exclusion of structural or accidental causes, the authors sought to explore if such a variation would differ between patients with or without atopic disorders. STUDY DESIGN: Case series with chart review. SETTING: NÄL Medical Centre Hospital, a secondary referral hospital. SUBJECTS AND METHODS: A total of 314 consecutive cases of esophageal bolus impaction from 2004 through 2009 were included and analyzed regarding seasonal variation in incidence. The analysis was repeated after exclusion of cases with sharp items, cancer, or atresia and again separately after subdividing this group according to presence of atopy. RESULTS: The overall incidence of esophageal bolus impaction was significantly higher during summer and fall than during the corresponding winter and spring period. In cases with atopic disorders and soft foods or meat bolus obstruction (n = 90), the incidence during the fall was significantly higher than that during the winter, and the incidence during the summer and fall was significantly higher than the corresponding incidence during the winter and spring. This variation was not present in patients without any signs or symptoms of atopy. CONCLUSIONS: There was a significant seasonal variation in the incidence of acute esophageal bolus impaction. This variation was pronounced in patients with a coexisting atopic diathesis but was nonsignificant in patients without atopy.