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INTRODUCTION: There are limited longitudinal data on the impact of chronic therapy on the natural history of eosinophilic esophagitis (EoE), a chronic allergic disease of the esophagus. The purpose of this study was to evaluate if patients with well-controlled EoE were less likely to develop fibrostenotic complications. METHODS: Subjects were identified from a database of pediatric patients with EoE at the Children's Hospital of Philadelphia started in 2000. Patients were then searched in adult medical records to identify patients who transitioned care. All office visits, emergency department visits, and endoscopic, histologic, and imaging reports were reviewed for the primary outcome of strictures and the secondary outcomes of food impactions and dysphagia. Cox proportional hazard regression was performed for outcomes. RESULTS: One hundred five patients were identified with the mean follow-up of 11.4 ± 4.9 years. 52.3% (n = 55) had a period of histologic disease control defined as ≥2 consecutive endoscopies with histologic remission. These patients were less likely to develop strictures compared with patients who did not have a period of histologic control (HR 0.232; 95% CI 0.084-0.64, P = 0.005). Patients who were diagnosed at younger ages were less likely to develop strictures. Presentation with dysphagia or impaction was associated with higher rate of stricture development. DISCUSSION: In this cohort study with > 10 years of follow-up, children with EoE with a period of histologic disease control and diagnosed at younger ages were less likely to develop esophageal strictures. While this suggests histologic remission is associated with reduction of remodeling complications, additional prospective data with long-term follow-up are needed.
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Patients with chronic diseases have increasingly turned to social media to discuss symptoms and share the challenges they face with disease management. The primary aim of this study is to use naturally occurring data from X (formerly known as Twitter) to identify barriers to care faced by individuals affected by eosinophilic esophagitis (EoE). For this qualitative study, the X application programming interface with academic research access was used to search for posts that referenced EoE between 1 January 2019 and 10 August 2022. The posts were identified as being either related to barriers to care for EoE or not. Those related to barriers to care were further categorized by the type of barrier that was expressed. A total of 8636 EoE-related posts were annotated of which 12.1% were related to barriers to care in EoE. The themes that emerged about barriers to care included: dietary challenges, limited treatment options, lack of community support, lack of physician awareness of disease, misinformation, cost of care, lack of patient belief in disease or trust in physician, and limited access to care. Saturation of themes was achieved. This study highlights barriers to care in EoE using readily accessible social media data that is not derived from a curated research setting. Identifying these obstacles is key to improving care for this chronic disease.
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BACKGROUND AND AIMS: Heartburn is the most common symptom seen in gastroenterology practice. We aimed to optimize cost-effective evaluation and management of heartburn. METHODS: We developed a decision analytic model from insurer and patient perspectives comparing 4 strategies for patients failing empiric proton pump inhibitors (PPIs): (1) PPI optimization without testing, (2) endoscopy with PPI optimization for all patients, (3) endoscopy with PPI discontinuation when erosive findings are absent, and (4) endoscopy/ambulatory reflux monitoring with PPI discontinuation as appropriate for phenotypic management. Health outcomes were respectively defined on systematic reviews of clinical trials. Cost outcomes were defined on Centers for Medicare and Medicaid Services databases and commercial multipliers for direct healthcare costs, and national observational studies evaluating healthcare utilization. The time horizon was 1 year. All testing was performed off PPI. RESULTS: PPI optimization without testing cost $3784/y to insurers and $3128 to patients due to lower work productivity and suboptimal symptom relief. Endoscopy with PPI optimization lowered insurer costs by $1020/y and added 11 healthy days/y by identifying erosive reflux disease. Endoscopy with PPI discontinuation added 11 additional healthy days/y by identifying patients without erosive reflux disease that did not need PPI. By optimizing phenotype-guided treatment, endoscopy/ambulatory reflux monitoring with a trial of PPI discontinuation was the most effective of all strategies (gaining 22 healthy days/y) and saved $2183 to insurers and $2396 to patients. CONCLUSIONS: Among patients with heartburn, endoscopy with ambulatory reflux monitoring (off PPI) optimizes cost-effective management by matching treatment to phenotype. When erosive findings are absent, trialing PPI discontinuation is more cost-effective than optimizing PPI.
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INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Humanos , Reproducibilidad de los Resultados , Trastornos de la Motilidad Esofágica/diagnóstico , Unión Esofagogástrica/diagnóstico por imagen , Manometría/métodos , Peristaltismo , Acalasia del Esófago/diagnósticoRESUMEN
BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) has a variable disease course. Currently, barium swallow (BaS) and manometric parameters are used to characterize clinically significant EGJOO. The esophagogastric junction distensibility index (EGJ-DI) measured via functional lumen imaging probe (FLIP) can provide complementary information. Our aim was to assess symptom response in patients with EGJOO and an abnormal EGJ-DI after botulinum toxin (BT) treatment. METHODS: A prospective cohort study of adults with idiopathic EGJOO was performed from September 2019 to March 2021. Patients with dysphagia underwent upper endoscopy with FLIP. If the EGJ-DI was abnormally low, BT was injected. Data examined included demographics, medical history, endoscopic and FLIP findings, BaS, manometry, and Eckardt score (ES). ES improvement was assessed via paired samples t-test. Pearson's chi-square tests were used to assess for associations. RESULTS: Of the 20 patients, 75% had an abnormal EGJ-DI and underwent BT injections. Mean ES for patients with abnormal EGJ-DIs significantly improved from baseline to 1, 3, and 6 month follow-up (P-values: 0.01, 0.05, and 0.02, respectively). There was a significant association between an abnormal EGJ-DI with delayed bolus transit and presence of rapid drink challenge panesophageal pressurization on manometry: P = 0.03 and P = 0.03. CONCLUSION: This prospective study revealed that an abnormal EGJ-DI can guide BT as assessed via symptomatic response. Additionally, abnormal EGJ-DI measurements were significantly associated with other parameters used previously to determine clinically relevant EGJOO. Larger follow-up studies are warranted to further elucidate guidance for therapy in EGJOO.
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Toxinas Botulínicas , Trastornos de Deglución , Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Gastropatías , Adulto , Trastornos de la Motilidad Esofágica/diagnóstico , Unión Esofagogástrica , Humanos , Manometría/métodos , Estudios Prospectivos , Gastropatías/complicacionesRESUMEN
INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.
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Trastornos de la Motilidad Esofágica/clasificación , Manometría/métodos , Peristaltismo/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Endoscopía Gastrointestinal , Trastornos de la Motilidad Esofágica/diagnóstico , Trastornos de la Motilidad Esofágica/fisiopatología , Esófago/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Patients affected by chronic illnesses have increasingly turned to social media to gather disease-related information and connect with other patients. Eosinophilic esophagitis (EoE) is a chronic disease with rapidly evolving management options. The aims of this study are to describe the current use of social media in EoE patients and caregivers, evaluate whether use of social media to learn about EoE is associated with higher medical knowledge of this disease, and evaluate social media factors that could result in improved patient and caregiver disease understanding. METHODS: We surveyed individuals 18 years or older in July 2020 who identified as either having EoE, or as being a caregiver for someone with EoE, through an invitation link sent to email subscribers of the American Partnership for Eosinophilic Disorders. RESULTS: Of the 212 survey responders, 82.5% used social media to learn about EoE. Caregivers were more likely to use social media than patients (OR 2.30, 95% CI 1.11-4.76). Social media use was not associated with higher knowledge of EoE. Distrust of posted content was the largest barrier to use and 87.7% of responders believed that physician contribution to posts would enhance the quality of information. CONCLUSIONS: In one of the first known studies to evaluate use of social media in the context of EoE, we found that a majority of patient and caregiver respondents use social media to learn about EoE. This highlights the potential opportunity to leverage social media to provide current and accurate EoE educational content for patients and caregivers.
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Esofagitis Eosinofílica , Medios de Comunicación Sociales , Cuidadores , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Esophagogastric junction outflow obstruction (EGJOO) is an abnormal finding on high-resolution manometry (HRM) characterized by an elevated median integrated relaxation pressure with some intact peristalsis.1 EGJOO is associated with heterogeneous symptoms, disease course, and response to treatment.1-4 It can be idiopathic or secondary with causes including malignancy, infiltrative disease, or structural etiology.1,3 Therefore, Chicago Classification of Esophageal Motility Disorders version 3.0 (CC v3.0) states a finding of EGJOO should prompt further investigation with cross-sectional imaging (CSI): endoscopic ultrasound (EUS) or computed tomography (CT) scan. However, there are limited data on the added yield of CSI to conventional modalities, namely esophagogastroduodenoscopy (EGD) and barium esophagram (BE). In previous studies, yield was small or unspecified.2,5-8 The aim of this study was to examine the yield of CSI for diagnosing secondary causes of EGJOO.
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Trastornos de la Motilidad Esofágica , Endoscopía del Sistema Digestivo , Unión Esofagogástrica/diagnóstico por imagen , Humanos , Manometría , PeristaltismoRESUMEN
BACKGROUND: Achalasia is an esophageal motor disorder that leads to swallowing dysfunction and weight loss. Nutritional risk in achalasia patients is not well defined. AIMS: The aims of this study were to define baseline body mass index (BMI), changes in weight, and nutritional risk over time in a large cohort of achalasia patients. METHODS: This was a retrospective cohort study of achalasia patients at a tertiary care center with documented BMI, symptom severity as per Eckardt score, and nutritional risk assessment as per the Malnutrition Universal Screening Tool, which considers BMI, degree of recent weight loss, and acuity of disease. RESULTS: Among the 337 patients presenting for achalasia management, 179 had confirmed disease. Upon presentation 69.8% of patients were classified as overweight or obese. Using the Malnutrition Universal Screening Tool, we found 50% of patients to be at moderate or high risk for malnutrition at presentation. Eckardt score (OR 1.15, 95% CI 1.05-1.26), duration of disease (OR for each additional month 1.04, 95% CI 1.01-1.08), and female gender (OR 1.76, 95% CI 1.02-3.03) were independent predictors of increased risk for malnutrition. Nutrition risk score decreased after therapy in 93.3% of patients. CONCLUSIONS: Despite a high prevalence of overweight and obese status in achalasia patients, many are at risk of developing nutritional complications secondary to rapid weight loss. This risk frequently resolves post-treatment. Regardless of baseline BMI, we recommend all patients undergo nutritional assessment to identify high-risk patients who may benefit from dietary intervention and expedited therapy.
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Índice de Masa Corporal , Acalasia del Esófago/complicaciones , Desnutrición/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Acalasia del Esófago/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Desnutrición/diagnóstico , Persona de Mediana Edad , Evaluación Nutricional , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Pérdida de Peso , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Esophageal diseases represent a wide variety of conditions affecting esophageal anatomy, physiology, and motility. Therapy focuses on pharmacotherapy and endoscopic or surgical management. Dietary therapy can be considered in management algorithms for specific esophageal diseases. This review focuses on outlining the literature related to dietary therapy in gastroesophageal reflux disease, eosinophilic esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. RECENT FINDINGS: Currently, data are strongest for dietary manipulation in eosinophilic esophagitis, specifically the six-food elimination diet. Dietary effects on gastroesophageal reflux disease are less clear, though newer research indicates that increased fiber with reduction in simple sugar intake may improve symptoms. In terms of Barrett's esophagus and esophageal adenocarcinoma, antioxidant intake may affect carcinogenesis, though to an unknown degree. Outcomes data regarding dietary manipulation for the management of esophageal diseases is heterogeneous. Given the rising interest in non-pharmacological treatment options for these patients, continued research is warranted.
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Enfermedades del Esófago/dietoterapia , Adenocarcinoma/dietoterapia , Esófago de Barrett/dietoterapia , Fibras de la Dieta/uso terapéutico , Esofagitis Eosinofílica/dietoterapia , Neoplasias Esofágicas/dietoterapia , Reflujo Gastroesofágico/dietoterapia , HumanosRESUMEN
BACKGROUND: Constipation and fecal incontinence (FI) are common and are often evaluated with anorectal manometry. Three-dimensional high-resolution anorectal manometry (HRAM) is a promising technology; however, implementation has been limited by lack of metrics and unclear clinical utility. AIM: To investigate the diagnostic utility of 3D HRAM compared to 2D HRAM. METHODS: Three-dimensional HRAM studies performed from April 2012 to October 2013 were identified and re-interpreted by two blinded investigators examining 3D function. Disagreements were resolved by a third investigator. Puborectalis (PR) visualization, focal defects, and dyssynergy were reported. Differences between groups were analyzed with Fisher's exact test. Discordance was analyzed with McNemar Chi-square test. RESULTS: Two hundred and twenty-one 3D HRAM studies were identified. Mean age and BMI were 52.2 ± 17.4 and 27.1 ± 7.5 years (81% female, 74% white). Most common indications for 3D HRAM were constipation (65%) and FI (28%). PR function was visualized in 81% (rest), 97% (squeeze), and 73% (strain). PR was visualized less often at rest in FI than constipation (68 vs. 85%, p = 0.007). Defects were identified twice as often in FI than constipation (19 vs. 10%, p = 0.113). Twenty-nine defects (86% anterior) were visualized on 3D HRAM. Inter-reader agreement was moderate for PR function (κ = 0.471), but fair for focal defects (κ = 0.304). CONCLUSIONS: PR function and focal defects can be visualized on 3D-HRAM with added diagnostic benefit compared to 2D. Fair inter-reader agreement for focal defects highlights the need for quantitative metrics.
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Canal Anal/diagnóstico por imagen , Estreñimiento/diagnóstico por imagen , Incontinencia Fecal/diagnóstico por imagen , Manometría/métodos , Recto/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Esophagogastric junction outflow obstruction (EGJOO) is a rapidly evolving diagnosis that can represent early or variant achalasia. Since the publication of the Chicago Classification version 4.0, the criteria for this diagnosis have been more stringent. Currently, the criteria include an elevated median integrated relaxation pressure (IRP) in both the supine and upright positions, elevated intrabolus pressure in at least 20% of supine swallows, dysphagia and/or chest pain, as well as an abnormal timed barium esophagram and/or impedance planimetry testing. Additionally, other secondary causes may result in an elevated IRP and must be excluded. The management of conclusive EGJOO is targeted therapy to the lower esophageal sphincter (LES), although treatment is not straightforward. Overall, adjuvant testing and data should be scrutinized for appropriateness of LES disruption. The spectrum of treatment options includes simple monitoring as well as more invasive therapies such as endoscopic dilation and myotomy. This article explores the newest criteria and management options for clinically relevant EGJOO.
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INTRODUCTION: Inflammation in eosinophilic esophagitis (EoE) often leads to esophageal strictures. Evaluating esophageal narrowing is clinically challenging. We evaluated esophageal distensibility as related to disease activity, fibrosis, and dysphagia. METHODS: Adult patients with and without EoE underwent endoscopy and distensibility measurements. Histology, distensibility, and symptoms were analyzed. RESULTS: Patients with EoE had significantly lower distensibilities than controls. We found a cohort with esophageal diameter under 15 mm despite lack of dysphagia. DISCUSSION: This study raises concern that current assessments of fibrostenosis are suboptimal. We describe a cohort with unrecognized slender esophagus that were identified through impedance planimetry measurements. This tool provides additional information beyond symptomatic, histologic, and endoscopic assessments.
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Trastornos de Deglución , Esofagitis Eosinofílica , Estenosis Esofágica , Adulto , Humanos , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/patología , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Estenosis Esofágica/diagnóstico , Estenosis Esofágica/etiología , Estenosis Esofágica/patología , Endoscopía GastrointestinalRESUMEN
OBJECTIVES: Pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) can be definitive therapies for achalasia; recent data suggest comparable efficacy. However, risk must also be considered. We reviewed the major complication rate of PD and LHM in a high-volume center and reviewed the corresponding literature. METHODS: We reviewed 12 years of our institution's achalasia treatment experience. During this interval, a consistent technique of PD was used utilizing Rigiflex dilators. Medical records were reviewed for post-procedure complications. We administered a telephone survey and examined medical records to assess efficacy of treatment. We also performed a systematic review of the literature for comparable clinical data and examined 80 reports encompassing 12,494 LHM and PD procedures. RESULTS: At our center, 463 achalasia patients underwent 567 PD or LHM procedures. In all, 78% of the PDs used a 30-mm Rigiflex dilator. In all, 157/184 (85%) patients underwent 1 or 2 PD without any subsequent treatment. There were seven clinically significant perforations; one from PD and six from LHM. There were no resultant deaths from these perforations; two deaths occurred within 30 days of LHM from unrelated causes. Complications and deaths post-PD were significantly fewer than those post-LHM (P=0.02). CONCLUSIONS: Esophageal perforation from PD at our high-volume center was less common than often reported and lower than that associated with LHM. We conclude that, in the hands of experienced operators using conservative technique, PD has fewer major complications and deaths than LHM.
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Dilatación/efectos adversos , Acalasia del Esófago/terapia , Perforación del Esófago/epidemiología , Perforación del Esófago/etiología , Esofagoplastia/efectos adversos , Esofagoplastia/métodos , Laparoscopía , Adulto , Anciano , Acalasia del Esófago/cirugía , Esofagoplastia/instrumentación , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Noroeste de Estados Unidos/epidemiología , Estudios Retrospectivos , Encuestas y Cuestionarios , TeléfonoRESUMEN
BACKGROUND: Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated. AIMS: To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice METHODS: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness. RESULTS: Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET) <4.0% on all days of monitoring with negative reflux-symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, AET >6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET >10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of <40 reflux events, AET <2.0% and a negative reflux-symptom association does not support escalation of anti-reflux treatment. In contrast, AET > 4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics. CONCLUSIONS: Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.
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Esofagitis Péptica , Reflujo Gastroesofágico , Humanos , Monitorización del pH Esofágico , Esofagitis Péptica/tratamiento farmacológico , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin ß4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. METHODS: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line-derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. RESULTS: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. CONCLUSIONS: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.
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Esofagitis Eosinofílica , Interleucina-4 , 5'-Nucleotidasa/uso terapéutico , Animales , Citocinas , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Homeostasis , Humanos , Hiperplasia/patología , Interleucina-13/farmacología , Interleucina-13/uso terapéutico , Interleucina-4/uso terapéutico , Ratones , Omeprazol/farmacología , Omeprazol/uso terapéutico , Células Madre/metabolismoRESUMEN
The esophagus plays a crucial role in oral nutrition and digestive pathophysiology. In addition, diet is now considered an important primary or augmentative therapy in several esophageal disease states. This review highlights common dietary therapies used in treating diseases of the esophagus as well as the underlying data that support such practices. Specially, diet and its relationship to swallowing dysfunction, motility disorders, malignancies, and inflammatory mucosal diseases such as gastroesophageal reflux disease and eosinophilic esophagitis is explored.
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Esófago de Barrett , Esofagitis Eosinofílica , Reflujo Gastroesofágico , Dieta , HumanosRESUMEN
BACKGROUND: Achalasia is an esophageal motility disorder characterized by esophagogastric junction (EGJ) dysfunction and impaired esophageal peristalsis with significant impact on quality of life. While the functional luminal imaging probe (FLIP) has been used to assess EGJ distensibility in achalasia, its clinical utility in pediatrics is limited due to absence of normative values and correlations with clinical outcomes in children. Thus, we sought to evaluate FLIP's use in a pediatric achalasia cohort undergoing dilations and non-achalasia controls. METHODS: We conducted a retrospective study of pediatric patients with achalasia who underwent FLIP before and immediately after balloon dilations and compared to a non-achalasia cohort. KEY RESULTS: Thirty patients with achalasia (mean age, 15.2 years; 40% female), including fourteen treatment-naïve and thirteen controls (mean age, 7.9 years; 61% female) were identified. Median EGJ distensibility index (EGJ-DI) 2.07 mm2 mmHg-1 and diameter (9.23 mm) in treatment-naïve patients were significantly lower compared to controls (EGJ-DI 6.8 mm2 mmHg-1 ; diameter 18.61 mm; (p < 0.001). Balloon dilations resulted in a significant increase in EGJ-DI immediately after the dilation, particularly in treatment-naïve patients (p < 0.001), and a significant improvement in Eckardt scores (p < 0.001). CONCLUSIONS & INFERENCES: Functional luminal imaging probe measurements of EGJ-DI in pediatric patients with achalasia are mostly consistent with adult findings. However, normal EGJ-DI is seen in symptomatic patients, including treatment-naive, highlighting the need for pediatric reference data. Balloon dilations achieve a significant increase in EGJ-DI with improvement in Eckardt scores, confirming the therapeutic value of dilations in achalasia management.