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BACKGROUND: A subset of patients with irritable bowel syndrome (IBS) develop their symptoms after gastroenteritis, referred to as postinfectious IBS (PI-IBS). PI-IBS is associated with low-grade intestinal inflammation. Previous studies have evaluated mesalamine, an anti-inflammatory drug, in patients with IBS. We evaluated the efficacy of long-acting mesalamine in patients with PI-IBS. METHODS: Sixty-one patients who developed diarrhea-predominant IBS (IBS-D) after gastroenteritis were randomized to receive either 2.4 g of long-acting mesalamine or placebo daily for 8-weeks. The symptoms assessed were abdominal pain, bloating, stool frequency, stool consistency, severity of diarrhea and constipation, satisfaction with bowel habits, and IBS affecting or interfering with life. Quality-of-life (QOL) was assessed using the IBS-QOL questionnaire. The prespecified primary outcome variable was the overall bowel symptom score (BSS) after 8-weeks of treatment. Effect sizes were expressed as standardized mean differences (Cohen's d). RESULTS: Fifty-four patients completed the 8-week treatment (n = 28 mesalamine, n = 26 placebo), 49 (91%) were male, and age range 23-71 years (mean ± SD 43 ± 13). Mesalamine demonstrated superior efficacy compared to placebo on the primary outcome variable, overall BSS (Cohen's d = 0.57, p = 0.042). Mesalamine was also superior for the secondary outcome of how much IBS affects your life in general (d = 0.72, p = 0.01). For the secondary outcomes of IBS symptoms, 7 of the 7 symptoms had trends of mesalamine superiority. For the secondary outcomes of IBS-QOL subscales, 8 of 9 had trends of mesalamine superiority. CONCLUSION: In patients with PI-IBS, long-acting mesalamine demonstrated to be effective in reducing IBS symptoms and improving QOL.
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Background and study aims In gastrointestinal endoscopy, biopsies must transit through the accessory channel and cap, presenting an opportunity for loss of tissue. We sought to determine the incidence of specimen retention in the accessory channel or cap and identify procedure characteristics associated with specimen retention. Patients and methods After completion of standard endoscopic procedures in which biopsies were obtained, the biopsy cap and accessory channel were inspected, brushed, and irrigated for any retained biopsy specimens according to a standard protocol. For controls, the same protocol was applied to procedures in which biopsies were not obtained. Specimen bottles from the recovery protocol were sent for pathological examination regardless of whether any visible tissue was present. Results A total of 216 outpatient procedures were included: 55 esophagogastroduodenoscopies (EGDs) and 50 colonoscopies in which biopsies were obtained and 56 EGDs and 55 colonoscopies in the control group. Retained specimens were found in either the cap or channel in 50 of 105 (48%). In 20 of 105 (19%), retained specimens were found just in the cap, in six of 105 (5.7%), retained specimens were found just in the channel, while in 24 of 105 (23%), retained specimens were found in both the cap and channel. Retained specimens were more likely to be found in EGDs compared to colonoscopies (58% vs. 36%, P = 0.031). No retained specimens were found in the control group. Conclusions Retained specimens are startingly common in standard gastrointestinal endoscopic procedures and could potentially change diagnoses and management. Quality improvement measures should be instituted to monitor prevalence of retained biopsies and methods to prevent them should be developed.
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BACKGROUND: Adequate colon preparation is a critical component of high-quality colonoscopy especially for inpatients undergoing colonoscopy for acute indications. Inpatient colonoscopy has a high incidence of inadequate preparations. We report implementation of a multifaceted quality improvement intervention to improve inpatient colonoscopy preparations. METHODS: Bowel preparation quality from inpatient colonoscopies performed for the 12 months prior to the comprehensive intervention were compared to colonoscopies performed for 12 months following the intervention. The intervention had multiple components including: 1) EMR-based colonoscopy preparation order set; 2) automated EMR alerts prompting nursing assessment of preparation progress; 3) standardized nursing charting processes for tracking preparation progress; and 4) standardized education for nursing staff and ordering providers on adequate colon preparation, assessment of colon preparation quality, and use of the above processes; and print and video patient education materials. RESULTS: Two hundred thirty-eight inpatient colonoscopies were performed in the preintervention assessment period and 163 colonoscopies in the postintervention period. Median preintervention Boston Bowel Preparation Score (BBPS) was 6 and 26% of patients had inadequate colon preparation. Median postintervention BBPS was 8 with 16% inadequate colon preparation (P=0.016). The postintervention group had less ASA class I patients and used a lower dose of fentanyl than the preintervention group. There were no other significant differences between the pre- and postintervention groups. CONCLUSIONS: Implementation of a comprehensive colon preparation quality intervention resulted in significantly improved inpatient colon preparation quality and decreased frequency of inadequate preparations. The intervention consisting of an EMR-based order-set, nursing alerts and charting process, and patient education materials is continually being refined.
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Catárticos , Pacientes Internos , Humanos , Colonoscopía/métodos , Colon , Mejoramiento de la CalidadRESUMEN
Background: Gastric intestinal metaplasia (GIM) is a premalignant gastric mucosal change that is often incidentally detected during esophagogastroduodenoscopy (EGD). Despite the established higher risk of gastric cancer associated with GIM, the incidence, prevalence, and outcomes data for GIM are limited in the United States (US), and practice patterns are highly variable. Objectives: Our primary objectives were to accurately identify incident histology-confirmed GIM cases and determine patient characteristics, endoscopy findings, Helicobacter pylori (HP) detection, and eradication treatment outcomes, as well as surveillance and follow-up recommendations. Design: We conducted a retrospective cohort study using administrative data. Methods: We first developed and validated a rule-based natural language processing tool to identify the patients with GIM on gastrointestinal pathology reports between 2011 and 2016. We then performed a manual chart review of all EGD procedures and associated pathology notes to confirm cases and obtain clinically relevant data. Results: In all, 414 patients with an index diagnosis of GIM were confirmed (prevalence = 2.5% of patients undergoing any EGD). A majority (52.4%) of patients were non-Hispanic white. The most common indication for EGD was abdominal pain (46.9%). A majority (55%) did not receive specific follow-up recommendations or were asked to see their primary care provider. HP testing was documented in 86% of patients, and detected in 94 patients (prevalence = 26.4%). Treatment was documented in 94.7% of cases, and eradication confirmed in only 34.8% of these cases. Conclusion: A large group of US patients with an index diagnosis of GIM was accurately identified. There was wide variability in clinical practice patterns including biopsy practice, HP treatment and eradication confirmation testing, and surveillance recommendations. This work demonstrates that there is a major unmet need for quality improvement efforts to standardize care for patients with GIM, a premalignant condition, and inform future prospective studies in a US population.
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BACKGROUND & AIMS: Familial clustering of eosinophilic esophagitis (EoE) has been described, and we report on the biopsy-assessed prevalence of esophageal eosinophilia (EE) in first-degree family members. The aim was to determine the prevalence of EE in first-degree adult relatives (FDRs) of EoE patients. METHODS: Index EoE patients diagnosed by EE (>15 eosinophils per high-power field) and proton pump inhibitor nonresponsiveness were identified and family trees were constructed. Adult FDRs were invited to undergo upper endoscopy with esophageal biopsies and to complete reflux, dysphagia, and allergy/atopy questionnaires. Questionnaire information was gathered only for those who responded as per institutional review board purview. Records from other children and adult FDRs with prior EoE diagnoses also were obtained when permission was obtained. Simple and multivariable logistic regression models were used to evaluate the unadjusted and odds ratios of EoE for demographic and clinical variables. RESULTS: A total of 239 FDRs from 37 index EoE patients were identified. Seventy-one of 239 adult (age, >18 y) FDRs completed endoscopy and questionnaires and 18 of 71 FDRs had EE. An additional 17 FDRs were confirmed to have EE after external medical record retrieval, resulting in a total of 35 of 239 (14.6%) FDRs with EE. Significantly more male FDRs had EE compared with female FDRs (P = .027). Proton pump inhibitors, dysphagia, gastroesophageal reflux disease, asthma, and reflux symptoms predicted EE in FDRs. FDRs who had EE reported hay fever, allergic eye symptoms, and food allergy more frequently than those without EE (P = .03, P = .001, and P = .02, respectively). Specifically, younger age, higher serum eosinophils, being male, and having food allergies all were associated with higher odds of EoE (P = .0211, P = .0031, P = .0362, and P = .0089, respectively). CONCLUSIONS: The prevalence of esophageal eosinophilia is extremely high and male-predominant in first-degree relatives of EoE patients. Symptoms of hay fever, allergic eye symptoms, and food allergy were predictors of EE in FDRs. Dysphagia did not predict esophageal eosinophilia. Family members of EoE patients are at risk for EE, particularly those who have atopic symptoms.
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Trastornos de Deglución , Esofagitis Eosinofílica , Hipersensibilidad a los Alimentos , Reflujo Gastroesofágico , Rinitis Alérgica Estacional , Adulto , Niño , Trastornos de Deglución/epidemiología , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/diagnóstico , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Gastritis , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/epidemiología , Humanos , Masculino , Inhibidores de la Bomba de Protones/uso terapéutico , Rinitis Alérgica Estacional/inducido químicamente , Rinitis Alérgica Estacional/complicacionesRESUMEN
The aim of this study was to test the effects of CPAP on moderately sedated patients undergoing colonoscopy. Our hypothesis was that CPAP can reduce the incidence and duration of obstructive apnea and hemoglobin oxygen desaturation in patients undergoing procedural sedation for colonoscopy. Two groups of consenting adult patients scheduled to undergo routine colonoscopy procedures and sedated with propofol and fentanyl were monitored in this study: control and intervention. Patients in the intervention group were connected via a facemask to a ventilator that delivered supplemental oxygen (100%) through a standard air-cushion mask. The mask had a built-in leak to facilitate CO2 clearance during CPAP. Patients in the control group received 2-10 L/min of oxygen via nasal cannula or non-rebreather mask. Subjects in the control group were collected in a prior study and used as historical controls. The primary outcome measures were the number of apneic events and the cumulative duration of apneic events. An apneic event was defined as a period longer than 10 s without respiration. The secondary outcome was the area under the curve (AUC) for the arterial oxygen saturation less than 90% versus time during sedative and analgesic administration (time (s) below threshold multiplied by percent below threshold). A desaturation event was defined as a period of time during which arterial oxygen saturation was less than 90%. 29 patients were enrolled in the intervention group and 156 patients were previously enrolled in the control group as part of an earlier study. The median number of apneic events in the control group was 7 compared to 0 in the intervention group. The intervention group experienced apnea less than 1% of the total procedure time compared to 17% in the control group (p < 0.001). There were no desaturation events observed in the 29 patients in the intervention group. In contrast, 27 out of 156 patients in the control group experienced a desaturation event. Average AUC of patients in the control group was 70%-s (time (s) * oxygen saturation below < 90%) (95% CI 32.34-108.60%) whereas the average AUC in intervention group patients was 0%-s (% time (s) * oxygen saturation < 90%) (95% CI 0-0%), p = 0.01. This preliminary study found that CPAP via a tight-fitting mask may be an effective tool to reduce the incidence and duration of obstructive apneic events as well as hemoglobin oxygen desaturation during lower endoscopy procedures that use propofol and fentanyl for sedation.Clinical Trial Registration ClinicalTrials.gov ID: NCT02623270. https://clinicaltrials.gov/ct2/show/NCT02623270 .
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Propofol , Adulto , Cánula , Colonoscopía , Sedación Consciente , Humanos , Respiración , Ventiladores MecánicosRESUMEN
We report a case series of 4 patients who underwent routine gastrointestinal endoscopy under moderate sedation and developed corneal injuries. Although corneal abrasion has been reported as the most common ocular complication during non-ocular surgery under general anesthesia, the risk for corneal abrasion during routine endoscopic procedures using moderate sedation has not been previously reported. Symptoms reported included ocular burning, scratchy sensation, redness, and pain reported post-procedure. Endoscopists and staff should be alert to the occurrence of this potentially serious complication, as this is paramount for its prevention, diagnosis, and management. Treatment of corneal abrasion includes referral to ophthalmology for close monitoring, pain management, pressure patch, and antimicrobial prophylaxis.
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Recent evidence suggests almost half of repeat esophagogastroduodenoscopy procedures (EGDs) are overused; this prior research relied on administrative data that are often inaccurate. Our primary objective was to determine and compare the accuracy of natural language processing and administrative data to manual chart review to identify dysphagia indications for EGD procedures within the national VA healthcare system. From 396,856 EGD notes identified from 2008-2014, we classified 119,920 as "index" procedures in 2010-2012. We compared the performance of our NLP to ICD codes to correctly identify dysphagia indications in the index EGD procedures and in repeat EGD procedures. We used linked pathology data to describe esophageal biopsies performed during these EGDs. NLP performed significantly better and identified significantly more index and repeat EGD procedures with dysphagia indications than ICD codes, which has critical implications for determining appropriateness of EGD procedures.
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BACKGROUND: Obesity is a significant health problem and additional therapies are needed to improve obesity treatment. OBJECTIVE: Determine the efficacy and safety of a 6-month swallowable gas-filled intragastric balloon system for weight loss. SETTING: Fifteen academic and private practice centers in the United States. METHODS: This was a double-blind, randomized sham-controlled trial of the swallowable gas-filled intragastric balloon system plus lifestyle therapy compared with lifestyle therapy alone for weight loss at 6 months in participants aged 22 to 60 years with body mass index 30 to 40 kg/m2, across 15 sites in the United States. The following endpoints were included: difference in percent total weight loss in treatment group versus control group was >2.1%, and a responder rate of >35% in the treatment group. RESULTS: Three hundred eighty-seven patients swallowed at least 1 capsule. Of participants, 93.3% completed all 24 weeks of blinded study testing. Nonserious adverse events occurred in 91.1% of patients, but only .4% were severe. One bleeding ulcer and 1 balloon deflation occurred. In analysis of patients who completed treatment, the treatment and control groups achieved 7.1 ± 5.0% and 3.6 ± 5.1% total weight loss, respectively, and a mean difference of 3.5% (Pâ¯=â¯.0085). Total weight loss in treatment and control groups were 7.1 ± 5.3 and 3.6 ± 5.1 kg (P < .0001), and body mass index change in the treatment and control groups were 2.5 ± 1.8 and 1.3 ± 1.8 kg/m2 (P < .0001), respectively. The responder rate in the treatment group was 66.7% (P < .0001). Weight loss maintenance in the treatment group was 88.5% at 48 weeks. CONCLUSIONS: Treatment with lifestyle therapy and the 6-month swallowable gas-filled intragastric balloon system was safe and resulted in twice as much weight loss compared with a sham control, with high weight loss maintenance at 48 weeks.
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Balón Gástrico/efectos adversos , Balón Gástrico/estadística & datos numéricos , Pérdida de Peso/fisiología , Adulto , Presión Sanguínea/fisiología , Método Doble Ciego , Endoscopía Gastrointestinal , Femenino , Humanos , Estilo de Vida , Lípidos/sangre , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. OBJECTIVE: This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. METHODS: The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. RESULTS: There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. CONCLUSIONS: This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives.
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Esofagitis Eosinofílica/genética , Familia , Familia de Multigenes , Linaje , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Interacción Gen-Ambiente , Genealogía y Heráldica , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , Familia de Multigenes/genética , Polimorfismo Genético , Grupos de Población , Riesgo , Utah , Adulto JovenRESUMEN
BACKGROUND: Non-anesthesia administered propofol (NAAP) has been shown to be a safe and effective method of sedation for patients undergoing gastrointestinal endoscopy. Bariatric surgery patients are potentially at a higher risk for sedation-related complications due to co-morbidities including obstructive sleep apnea. The outcomes of NAAP in bariatric patients have not been previously reported. METHODS: In this retrospective cohort study, severely obese patients undergoing pre-surgical outpatient esophagogastroduodenoscopy (EGD) were compared to non-obese control patients (BMI ≤ 25 kg/m2) undergoing diagnostic EGD at our institution from March 2011-September 2015 using our endoscopy database. Patients' demographics and procedural and recovery data, including any airway interventions, were statistically analyzed. RESULTS: We included 130 consecutive pre-operative bariatric surgical patients with average BMI 45.8 kg/m2 (range 34-80) and 265 control patients with average BMI 21.9 kg/m2 (range 14-25). The severely obese group had a higher prevalence of sleep apnea (62 vs 8%; p < 0.001), experienced more oxygen desaturations (22 vs 7%; p < 0.001), and received more chin lift maneuvers (20 vs 6%; p < 0.001). Advanced airway interventions were rarely required in either group and were not more frequent in the bariatric group. CONCLUSIONS: With appropriate training of endoscopy personnel, NAAP is a safe method of sedation in severely obese patients undergoing outpatient upper endoscopy.
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Sedación Consciente , Gastroscopía , Hipnóticos y Sedantes/administración & dosificación , Obesidad Mórbida/cirugía , Propofol/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Complicaciones Posoperatorias , Prevalencia , Estudios Retrospectivos , UtahRESUMEN
BACKGROUND AND STUDY AIMS: Pneumoperitoneum following PEG placement has been reported in up to 60â% of cases, and while usually benign and self-limited, it can lead to evaluation for suspected perforation. This study was designed to determine whether using CO2 compared to ambient air for insufflation during PEG reduces post-procedure pneumoperitoneum. PATIENTS AND METHODS: Prospective, double-blind, randomized trial of 35 consecutive patients undergoing PEG at a single academic medical center. Patients were randomized to insufflation with CO2 or ambient air. The primary outcome was pneumoperitoneum determined by left-lateral decubitus abdominal x-rays 30 minutes after PEG placement. Secondary endpoints included abdominal distention, pain, and bloating. RESULTS: PEG was successfully placed in 17 patients using CO2 and 18 patients using ambient air. Three patients in each arm were unable or declined to have x-rays completed and were excluded. Pneumoperitoneum was identified in 2/14 (14.3â%) using CO2 and 8/15 (53.3â%) using ambient air (Pâ=â0.05). There was no significant difference in abdominal distention, visual analog scale (VAS) scores for pain or bloating between CO2 and ambient air. CONCLUSION: Utilizing CO2 significantly reduces the frequency of post-procedural pneumoperitoneum compared to use of ambient air during PEG placement, with no difference in waist circumference, pain or bloating between CO2 and ambient air. CO2 appears to be safe and effective for use and may be the insufflation agent of choice during PEG.
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BACKGROUND: Inadequate bowel preparation is the most common cause of failed colonoscopy, and repeat failure occurs in more than 20 % of follow-up attempts. Limited data suggest that next-day follow-up may reduce the risk for repeat inadequate preparation. OBJECTIVE: Evaluate differences in prep quality with next-day follow-up after initial inadequate preparation. DESIGN: Retrospective study. SETTING: Academic center. PATIENTS: Outpatient screening and surveillance colonoscopies between 7/2002 and 6/2007. INTERVENTION: Comparison of next-day versus any other day ("non-next-day") repeat colonoscopy outcomes. MAIN OUTCOME MEASUREMENTS: Aronchick scale, polyp and adenoma detection rates. RESULTS: Of 20,798 initial colonoscopies, 857 (4.1 %) had inadequate preparation. 460 (54 %) were lost to follow-up. One hundred and fourteen (13 %) had next-day and 283 (33 %) had non-next-day colonoscopy with mean follow-up of 8.8 months. On follow-up examination, 29.8 % of next-day and 23.3 % of non-next-day colonoscopies had inadequate bowel preparation (p = 0.48). The adenoma detection rate for the next-day group improved from 3.5 to 38.6 % on follow-up, compared to 20.5 and 36.8 % in the non-next-day group. There was no significant difference between groups in detection of total adenoma (p = 0.73) or advanced adenomas (p = 0.20) on follow-up examinations. LIMITATIONS: Retrospective design, differences in baseline colonoscopy characteristics. CONCLUSION: The results confirm the need for repeat examination after a colonoscopy with inadequate bowel prep, as there was substantial increase in adenoma detection on follow-up. There were no differences in outcomes between next-day versus non-next-day colonoscopy. These data support repeating after inadequate colonoscopy within 1 year as convenient for patient and physician.
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Pólipos Adenomatosos/patología , Colon/patología , Neoplasias del Colon/patología , Pólipos del Colon/patología , Colonoscopía , Laxativos/administración & dosificación , Polietilenglicoles/administración & dosificación , Irrigación Terapéutica/métodos , Centros Médicos Académicos , Administración Oral , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
BACKGROUND & AIMS: Eosinophilic esophagitis is usually triggered by foods, by unclear mechanisms. We evaluated the roles of IgE and IgG4 in the development of eosinophilic esophagitis. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial of adults with eosinophilic esophagitis given an antibody against IgE (omalizumab, n = 16) or placebo (n = 14) every 2-4 weeks for 16 weeks, based on weight and serum level of IgE. Endoscopy was performed, esophageal biopsy specimens were collected, and symptoms were assessed at baseline and at 16 weeks. Maximum numbers of eosinophils/high-power field were determined. Homogenates of esophageal biopsy specimens from 11 subjects with eosinophilic esophagitis and 8 without (controls) were assessed for IgM, IgA, and IgG subclasses. In a retrospective analysis, we performed immunofluorescence analysis of IgG4 in fixed esophageal tissues from 2 patients with eosinophilic esophagitis who underwent esophagectomy and 47 consecutive autopsies (controls). We also performed immunofluorescence analysis of IgG4 in esophageal mucosal biopsy specimens from 24 subjects with eosinophilic esophagitis and 9 without (controls). Finally, sera were collected from 15 subjects with eosinophilic esophagitis and from 41 without (controls), and assayed for total and food-reactive IgG4. RESULTS: Omalizumab did not alter symptoms of eosinophilic esophagitis or eosinophil counts in biopsy samples compared with placebo. Homogenates of esophageal tissues from patients with eosinophilic esophagitis had a 45-fold increase in IgG4 compared with controls (P < 3 × 10(-5)), but no significant increases in other IgG subclasses, IgM, or IgA. Sparse stromal deposits resembling immune complexes were found in 2 of 5 eosinophilic esophagitis biopsy specimens based on ultrastructural analysis. Esophagectomy samples from 2 patients with eosinophilic esophagitis contained 180 and 300 IgG4 plasma cells/maximal high-power field, mainly in the deep lamina propria; these levels were greater than in tissues from controls. Fibrosis essentially was exclusive to the lamina propria. Granular extracellular IgG4 was detected in biopsy specimens from 21 of 24 patients with eosinophilic esophagitis, but in none of the specimens from 9 controls (P = 6 × 10(-6)). The total serum level of IgG4 increased only slightly in patients with eosinophilic esophagitis, compared with controls. Subjects with eosinophilic esophagitis had increased serum levels of IgG4 that reacted with milk, wheat, egg, and nuts-the 4 foods that most commonly trigger this condition (P ≤ 3 × 10(-4) for each food). CONCLUSIONS: In a prospective trial, omalizumab did not reduce symptoms of eosinophilic esophagitis or tissue eosinophil counts compared with placebo. This finding, along with observed granular deposits of IgG4, abundant IgG4-containing plasma cells, and serum levels of IgG4 reactive to specific foods, indicate that, in adults, eosinophilic esophagitis is IgG4-associated, and not an IgE-induced allergy. ClinicalTrials.gov number: NCT 00123630.
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Esofagitis Eosinofílica/inmunología , Esófago/inmunología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/metabolismo , Inmunoglobulina G/metabolismo , Adulto , Anciano , Antialérgicos/uso terapéutico , Anticuerpos Antiidiotipos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores/sangre , Biomarcadores/metabolismo , Biopsia , Método Doble Ciego , Esofagitis Eosinofílica/sangre , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagoscopía , Esófago/efectos de los fármacos , Hipersensibilidad a los Alimentos/sangre , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Omalizumab , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , UtahRESUMEN
BACKGROUND: In patients with eosinophilic esophagitis (EoE), eosinophils accumulate and release granule proteins onto esophageal epithelium. However, little is understood about the mechanism of eosinophil degranulation. OBJECTIVE: To determine and quantify eosinophil degranulation patterns, we studied esophageal biopsy specimens from both the proximal and distal esophagi of 9 randomly selected patients with EoE. METHODS: The specimens were fixed in glutaraldehyde, embedded, sectioned, and imaged by means of transmission electron microscopy. Eosinophils and their granules were identified by their distinctive morphology, and all eosinophils and granules were imaged. A total of 1672 images from 18 esophageal specimens were evaluated and graded. Eosinophils were categorized based on membrane integrity and by cytoplasmic vesiculation as evidence of piecemeal degranulation. Granules were categorized based on reversal of staining (eosinophil granule core lightening) and localization within and outside the cells. RESULTS: The results revealed that greater than 98% of eosinophils infiltrating the esophagus in patients with EoE demonstrate morphologic abnormalities ranging from granule changes with reversal of staining to marked cytoplasmic vesiculation to loss of cellular membrane integrity with cytolytic disruption and release of intact membrane-bound granules into the tissues. Approximately 81% of eosinophils showed membrane disruption. Extracellular granules were abundant in at least 70% of the images, and approximately 50% of these granules showed reversal of staining. On the basis of the prominence of tubulovesicular development, piecemeal degranulation appears closely related to the other morphologic changes seen in patients with EoE. CONCLUSION: These findings reveal that eosinophils in esophageal biopsy specimens from patients with EoE are abnormal, with greater than 80% showing cytolysis, and therefore that evaluation by means of light microscopy after hematoxylin and eosin staining might not accurately reflect eosinophil involvement.