Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. METHODS: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). RESULTS: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. CONCLUSIONS: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.

Case-control study of Clostridioides difficile in a rural health care area. / Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural.

OBJECTIVE: To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). PATIENTS AND METHODS: Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. RESULTS: Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. CONCLUSIONS: The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.

Anthropometric assessment of schoolchildren from the La Mancha-Centro health area. Comparison with the Spanish Cross-Sectional Growth Study 2010.

OBJECTIVES: To determine weight, height and body mass index (BMI) of schoolchildren from the La Mancha-Centro health area and compare them with those determined by the Spanish Cross-sectional Growth Study 2010 (SCGS-2010). METHODS: Cross-sectional study of 954 schoolchildren aged 6-12 years. Mean, standard deviation, and percentile distributions of weight, height, and BMI by gender and age were obtained. Differences in each 6-month age group were analyzed. RESULTS: There was a progressive increase in BMI with age, which was significant in girls from nine years of age on and in boys from 8.5 years on. From age 10, average BMI was 2.3 kg/m2 higher than at younger ages (p < 0.001). The biggest difference between genders occurred at age 12: 2 ± 0.98 kg/m2 higher in boys (p = 0.042). Overall, no significant differences were found in weight, height and BMI vs. SCGS-2010, although mean weight of male children from La Mancha-Centro aged between 8.5 and 11.5 years was 3.9 kg higher than that of the rest of Spanish male children. CONCLUSIONS: Anthropometric parameters of schoolchildren from La Mancha-Centro do not significantly differ from national standards; however, preadolescent males from La Mancha-Centro weigh almost 4 kg more.

OBJETIVOS: Determinar peso, talla e índice de masa corporal (IMC) de escolares del área de salud La Mancha-Centro y compararlos con los definidos en el Estudio Transversal Español de Crecimiento 2010 (ETEC-2010). MÉTODOS: Estudio transversal de 954 escolares entre 6 y 12 años. Se obtuvieron media, desviación estándar y distribuciones percentilares de peso, talla e IMC por sexo y edad. Se analizaron las diferencias en cada grupo semestral de edad. RESULTADOS: Existió incremento progresivo del IMC con la edad, significativo en las niñas a partir de los nueve años y en los niños desde los 8.5 años. Desde los 10 años, el IMC promedio resultó 2.3 kg/m2 superior al de edades menores (p < 0.001); la mayor diferencia entre los sexos ocurrió a los 12 años: 2 ± 0.98 kg/m2 más en los varones (p = 0.042). Globalmente no se hallaron diferencias significativas de peso, talla e IMC con el ETEC-2010, aunque el peso medio de los niños manchegos de 8.5 a 11.5 años fue 3.9 kg mayor que el del resto de los niños españoles. CONCLUSIONES: Los parámetros antropométricos de los escolares manchegos no difieren de los estándares nacionales; sin embargo, los varones preadolescentes manchegos pesan casi 4 kg más.

Validation of the Ramsay scale for invasive procedures under deep sedation in pediatrics.

BACKGROUND: The Ramsay scale is the most widely used scale during pediatric procedures although it has not been formally validated. OBJECTIVE: To validate the Ramsay scale during invasive procedures under sedation in pediatrics. METHODS: A prospective analytic study was conducted in two hospitals. All patients ≥6 months that were undergoing invasive procedures under sedation were enrolled. All were recorded, and these videos were edited and randomized. 150 videos were scored by four observers (a pediatrician, a pediatric intensive care unit nurse, an anesthetist, and an operating room nurse). All videos were scored with the Ramsay scale and University of Michigan Sedation Scale. Observers were blinded to drug administration. Construct validity was measured through Wilcoxon test paired samples after administration of sedatives. Criterion validity, intra-observer reliability, and interobserver correlation were evaluated by comparing the scores of the scales using Spearman's correlation coefficient. Interobserver agreement was measured using the intraclass correlation coefficient. To assess test-retest reliability, 50 videos were randomly selected and reevaluated. RESULTS: Sixty-five patients were included. Construct validity was demonstrated through changes in the Ramsay scale scoring after administration of sedatives (p < .0001). Regarding criterion validity, the Ramsay scale had a high correlation with the UMSS (ρ = 0.621). Intra-observer agreement was ρ = 0.884. The Ramsay scale showed interobserver reliability with an intraclass correlation coefficient = 0.94 when comparing it with the University of Michigan Sedation Scale. Internal consistency was α = 0.91. Regarding applicability, in our study, it was applied in two hospitals in different areas by four professionals from distinct categories. CONCLUSIONS: The Ramsay scale is valid, reliable, and applicable to monitoring sedation for invasive procedures under deep sedation in pediatrics.

Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice.

BACKGROUND & AIMS: Topical steroids, proton pump inhibitors (PPIs), and dietary interventions are recommended first- and second-line therapies for eosinophilic esophagitis (EoE). We investigated differences in their effectiveness in a real-world, clinical practice cohort of patients with EoE. METHODS: We collected data on the efficacy of different therapies for EoE (ability to induce clinical and histologic remission) from the multicenter EoE CONNECT database-a database of patients with a confirmed diagnosis of EoE in Europe that began in 2016. We obtained data from 589 patients, treated at 11 centers, on sex, age, time of diagnosis, starting date of any therapy, response to therapy, treatment end dates, alternative treatments, and findings from endoscopy. The baseline endoscopy was used for diagnosis of EoE; second endoscopy was performed to evaluate response to first-line therapies. After changes in treatment, generally because lack of efficacy, a last endoscopy was performed. The time elapsed between endoscopies depended on the criteria of attending physicians. Clinical remission was defined by a decrease of more than 50% in Dysphagia Symptom Score; improvement in symptoms by less than 50% from baseline was considered as clinical response. Histologic remission was defined as a peak eosinophil count below 5 eosinophils/hpf. A peak eosinophil count between 5 and 14 eosinophils/hpf was considered histologic response. We identified factors associated with therapy selection and effectiveness using χ2 and multinomial logistic regression analyses RESULTS: PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%). Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%). Among the 344 patients who switched to a second-line therapy, dietary interventions were selected for 47.1% of patients, followed by PPIs (for 29.1%) and topical steroids (for 18.6%). Clinical and histologic remission or response was achieved by 80.7% of patients treated with topical steroids, 69.2% of patients given PPIs, and 41.7% of patients on empiric elimination diets. Multivariate analyses found the stricturing phenotype of EoE to be associated with selection of topical steroids over PPIs as the first-line therapy; lack of fibrotic features at initial endoscopy was associated with selection of elimination diets over topical steroids as a second-line therapy. The recruiting center was significantly associated with therapy choice; second-line treatment with topical steroids or PPIs were the only variables associated with clinical and histologic remission. CONCLUSIONS: In an analysis of data from a large cohort of patients with EoE in Europe, we found topical steroids to be the most effective at inducing clinical and histologic remission, but PPIs to be the most frequently prescribed. Treatment approaches vary with institution and presence of fibrosis or strictures.

Effects of cord milking in late preterm infants and full-term infants: A systematic review and meta-analysis.

BACKGROUND: Umbilical cord milking (UCM) consists of performing several milkings of the cord from the placenta to the newborn. The objective was to evaluate the effects of UCM on newborns ≥34 weeks' gestation. METHODS: Searches were conducted in MEDLINE, EMBASE, CINAHL, the Cochrane Database of Clinical Trials, and the clinicaltrails.gov database for randomized clinical trials (RCT), with no time or language restrictions, and for articles that compared UCM with other strategies. The main results were initial hemoglobin and hemoglobin after 6 weeks. The data were collected by two reviewers and the quality of the studies was assessed using the Cochrane Manual methodology. RESULTS: The sample included 1845 newborns in 10 RCTs. The use of UCM in ≥34 weeks' gestation newborns was not related to initial hemoglobin levels (pooled weighted mean difference: (PWMD = 0.40 g/L [-0.16 to 0.95]) or after 6 weeks (PWMD = 0.07 g/L [-0.29 to 0.27]). A reduction in hemoglobin levels was also observed at 6 weeks when the control group had undergone late clamping (PWDM = 0.16g/L [-0.26 to -0.06]). CONCLUSIONS: UCM produced no differences in hematologic variables for newborns with ≥34 weeks of gestation relative to controls. However, a slight decrease in hemoglobin levels is observed at 6 weeks when the control group is made up of newborns with late clamping.

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study.

BACKGROUND: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers. OBJECTIVE: We sought to assess the effectiveness of a step-up dietary strategy for EoE. METHODS: We performed a prospective study conducted in 14 centers. Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten-containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food-group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy. RESULTS: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%. CONCLUSIONS: A TFGED diet achieves EoE remission in 43% of children and adults. A step-up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process.

Response to Symptoms and Prehospital Delay in Stroke Patients. Is It Time to Reconsider Stroke Awareness Campaigns?

BACKGROUND: Despite recent advances in acute stroke care, reperfusion therapies are given to only 1%-8% of patients. Previous studies have focused on prehospital or decision delay. We aim to give a more comprehensive view by addressing different time delays and decisions. METHODS: A total of 382 patients with either acute stroke or transient ischemic attack were prospectively included. Sociodemographic and clinical parameters and data on decision delay, prehospital delay, and first medical contact were recorded. Multivariate logistic regression analyses were conducted to identify factors related to decision delay of 15 minutes or shorter, calling the Extrahospital Emergency Services, and prehospital delay of 60 minutes or shorter and 180 minutes or shorter. RESULTS: Prehospital delay was 60 minutes or shorter in 11.3% of our patients and 180 minutes or shorter in 48.7%. Major vascular risk factors were present in 89.8% of patients. Severity was associated with decision delay of 15 minutes or shorter (odds ratio [OR] 1.08; confidence interval [CI] 1.04-1.13), calling the Extrahospital Emergency Services (OR 1.17; CI 1.12-1.23), and prehospital delay of 180 minutes or shorter (OR 1.08; CI 1.01-1.15). Adult children as witnesses favored a decision delay of 15 minutes or shorter (OR 3.44; CI 95% 1.88-6.27; P < .001) and calling the Extrahospital Emergency Services (OR 2.24; IC 95% 1.20-4.22; P = .012). Calling the Extrahospital Emergency Services favored prehospital delay of 60 minutes or shorter (OR 5.69; CI 95% 2.41-13.45; P < .001) and prehospital delay of 180 minutes or shorter (OR 3.86; CI 95% 1.47-10.11; P = .006). CONCLUSIONS: Severity and the bystander play a critical role in the response to stroke. Calling the Extrahospital Emergency Services promotes shorter delays. Future interventions should encourage immediately calling the Extrahospital Emergency Services, but the target should be redirected to those with known risk factors and their caregivers.

Xylose Improves Antibiotic Activity of Chloramphenicol and Tetracycline against K. pneumoniae and A. baumannii in a Murine Model of Skin Infection.

Increased resistance to antimicrobials in clinically important bacteria has been widely reported. The major mechanism causing multidrug resistance (MDR) is mediated by efflux pumps, proteins located in the cytoplasmic membrane to exclude antimicrobial drug. Some efflux pumps recognize and expel a variety of unrelated antimicrobial agents, while other efflux pumps can expel only one specific class of antibiotics. Previously, we have reported that xylose decreases the efflux-mediated antimicrobial resistance in Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii in vitro. In this work, we assessed the effectiveness of combining xylose with antibiotics to kill resistant Acinetobacter baumannii and Klebsiella pneumoniae in a murine model of skin infection. Skin infections were established by seeding 109 bacteria onto eroded skin of mice. Mice treated with the antibiotic alone or with a mixture of glucose and antibiotics or xylose and antibiotics were compared to a control group that was infected but received no further treatment. We observed that the mixtures xylose-tetracycline and xylose-chloramphenicol produced a decrease of at least 10 times viable Acinetobacter baumannii and Klebsiella pneumoniae recovered from infected skin, compared with mice treated with the antibiotic alone. Our results show that xylose improves the antibiotic activity of tetracycline and chloramphenicol against efflux-mediated resistance Acinetobacter baumannii and Klebsiella pneumoniae, in a murine model of skin infection. We envision these combined formulations as an efficient treatment of skin infections with bacteria presenting efflux-mediated resistance, in both humans and animals.

Association between atopic manifestations and eosinophilic esophagitis: A systematic review and meta-analysis.

BACKGROUND: Eosinophilic esophagitis (EoE) has repeatedly been associated with atopic manifestations, which are reported more frequently in these patients than in the general population. OBJECTIVE: To systematically assess the evidence and strength of the associations between EoE and atopy. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for case-control studies comparing the frequency of atopic diatheses among patients with EoE and control subjects representing the general population without EoE. Using random-effects meta-analyses, we calculated summary estimates, including 95% confidence intervals (CIs), for bronchial asthma, atopic rhinitis, and eczema. Publication bias risks were assessed by means of funnel plot analysis and specific statistical tests. RESULTS: Of the 2,954 references identified, data were collected from 21 studies, including a total of 53,542 patients with EoE and 54,759 controls. The criteria for defining a diagnosis of atopy in patients with EoE or controls was not structurally considered in most of the studies. Overall, allergic rhinitis was significantly more common among patients with EoE compared with control subjects (odds ratio [OR], 5.09; 95% CI, 2.91-8.90; I2 = 86.7%) as were bronchial asthma (OR, 3.01; 95% CI, 1.96-4.62; I2 = 84.5%) and eczema (OR, 2.85; 95% CI, 1.87-4.34; I2 = 57.1%). Food allergies and other atopic conditions were also assessed. No significant publication bias was found for studies dealing with allergic rhinitis and eczema in EoE. CONCLUSION: Despite pointing to a significant association between atopy and EoE, most of the studies provided no normalized diagnostic criteria for atopy. Further research should provide clear and standardized definitions of such conditions. TRIAL REGISTRATION: www.crd.york.ac.uk/PROSPERO Trial Identifier: CRD42016036161.

The Use of the Fracture Risk Assessment (FRAX®) Tool in Predicting Risk of Fractures in Patients With Inflammatory Bowel Disease: A Systematic Review.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is associated with an increased prevalence of osteoporosis and osteopenia. We aim to evaluate the use of the World Health Organization Fracture Risk Assessment (FRAX®) tool in these patients to assess 10-yr risk of fracture. Electronic searches were performed with key words relating to IBD and FRAX in the MEDLINE, EMBASE, and SCOPUS databases. Summary estimates were calculated. A fixed or random-effects model was used depending on heterogeneity (I2). The search yielded 146 references; 7 that included research carried out in adult patients, were used in the systematic review and quantitative summary. No significant publication bias was noted according to the Harbord test. The 10-yr probability of hip and major osteoporotic fracture in adult IBD patients was 1.03% (95% confidence interval [CI]: 0.37%-2%; I2 = 0%) and 4.05% (95% CI: 2.61%-5.79%; I2 = 49%), respectively. In those patients with Crohn's disease, hip and major osteoporotic fractures calculated with FRAX increased to 1.74% (95% CI: 0.42%-3.93%; I2 = 37.5%) and 6.65% (95% CI: 2.97%-11.66%; I2 = 8.7%), respectively. Risks of fracture in adults with ulcerative colitis were provided by a single study only. The FRAX tool has been limitedly used in patients with IBD; however, the evidence currently available only shows a modest increase in the 10-yr risks of bone fracture and does not support unequivocally the need for specific interventions. Further well-designed studies are needed to confirm the results obtained from this systematic review.

Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Proton pump inhibitor (PPI) therapy might lead to clinical and histologic remission in a significant proportion of patients with symptomatic esophageal eosinophilia (>15 eos/high-power field). We aimed to evaluate systematically the efficacy of PPI therapy for these patients. METHODS: A search in MEDLINE, EMBASE, and SCOPUS databases, and the American Gastroenterological Association Institute, American College of Gastroenterology, and United European Gastroenterology meetings abstract books, was performed. Primary outcomes were clinical response and histologic remission (<15 eos/high-power field) after PPI therapy. Secondary outcomes were the influence on the response to PPIs of age group, study design/quality, PPI type, doses and interval dosing, and pH monitoring results. Data were pooled using a random-effects model. RESULTS: Thirty-three studies (11 prospective studies) comprising 619 patients with symptomatic esophageal eosinophilia (188 children and 431 adults) were included. PPI therapy led to a clinical response in 60.8% (95% confidence interval, 48.38%-72.2%; I(2) = 80.2) and histologic remission in 50.5% (95% confidence interval, 42.2%-58.7%; I(2) = 67.5) of patients. No differences were observed regarding the study population (children vs adults), the type of publication, or its quality. PPIs were nonsignificantly more effective in prospective studies (52.6% vs 39.1%) administered twice daily compared with once daily (55.9% vs 49.7%), and with pathologic pH monitoring (65.4% vs 49.3%). A significant publication bias in favor of studies reporting histologic responses to PPIs was observed. CONCLUSIONS: PPI therapy induces clinicohistologic remission in half of patients with symptomatic esophageal eosinophilia. This finding should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias.

Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis.

BACKGROUND & AIMS: Various dietary interventions have been used to treat patients with eosinophilic esophagitis (EoE), yielding varied results. This systematic review assesses the efficacy of different dietary therapies in inducing disease remission. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for studies investigating the efficacy of dietary interventions (reducing infiltration by immune cells <15 eosinophils/high-power field in esophageal biopsies) for pediatric and adult patients with EoE. Summary estimates, including 95% confidence intervals (CI), were calculated for exclusive feeding with amino acid-based elemental formulas, allergy test result-directed food elimination diets, and 6-food elimination diets (SFED). A fixed- or random-effects model was used depending on heterogeneity (I(2)); publication bias risks were assessed by means of funnel plot analysis. RESULTS: The search yielded 581 references; of these, 33 were included in the quantitative summary. We analyzed data on a total of 1317 patients with EoE (1128 children and 189 adults) who received different dietary treatments. Elemental diets were effective for 90.8% of cases (95% CI, 84.7%-95.5%; I(2) = 52.3%), SFED for 72.1% (95% CI, 65.8%-78.1%; I(2) = 0), and allergy test result-directed food elimination for 45.5% of cases (95% CI, 35.4%-55.7%; I(2) = 75.1%). Additional strategies (elimination of cow's milk, gluten-free diets, and 4-food elimination diet) were also evaluated. Adults vs children had no significant differences in remission after dietary interventions (67.2% vs 63.3%). CONCLUSIONS: Dietary interventions are effective in producing histologic remission in patients with EoE. Elemental diets and SFEDs were the most effective, achieving <15 eosinophils/high-power field in 90.8% and 72.1% of patients, respectively.

Efficacy of Dietary Treatment for Inducing Disease Remission in Eosinophilic Gastroenteritis.

OBJECTIVES: Various dietary interventions have been used to treat patients with eosinophilic gastroenteritis (EGE). Concrete evidence as to the effectiveness of such treatments in inducing disease remission is, however, lacking. The aim of the study was to systematically review the efficacy of dietary therapies in inducing EGE remission. METHODS: We performed a systematic search for the MEDLINE, EMBASE, and SCOPUS libraries for studies investigating the efficacy of dietary interventions (in both histological and symptomatic remission) for children and adults with EGE and colitis. RESULTS: The search yielded 490 references; 30 were included in the review, with most of these references being "low-quality" individual cases or short case series. No significant publication bias was found. Elemental diets in children were linked to 75.8% of clinical improvement, but few of these patients underwent a histological evaluation. Allergy-testing results have been used scarcely in EGE. Empiric elimination of allergy-associated foods was the most commonly used option. The variable results in terms of symptom relief, however, were scarcely accompanied by histological confirmation. Clinical and methodological heterogeneity hindered the performance of quantitative summaries for the efficacy of dietary therapies in inducing disease remission. CONCLUSIONS: Symptomatic improvements reported for dietary treatment in EGE by most of the available literature are questionable because of the lack of objective evaluation of clinical changes and the very limited assessment of histological remission. Because of the relative lack of well-designed, high-quality studies, the unequivocal use of dietary treatment for patients with EGE and colitis cannot be supported. Further research should be undertaken.

Association between medication and intestinal intussusception in children: a case-crossover study.

OBJECTIVES: This study aimed to assess the association between the appearance of intussusception in children and medication intake in the immediately preceding period (2-15 days). METHODS: A case-crossover design was used. We selected cases of children admitted with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, 860) to the major hospitals in the city of Valencia, Spain, from 2006 to 2009. We then estimated the association between the episode of intussusception and the intake of prescription medication during the preceding 2, 7, and 15 days (case period) and for the same time window 1, 2, 3, and 4 months prior (control period). Data on previous drug administration were obtained from the Pharmaceutical Service Manager System. RESULTS: A total of 95 cases (65.3% boys and 34.7% girls) were selected; 76.6% were younger than the age of 2 years. The association between intussusception and prior drug use varied depending on the exposure window: 15-day odds ratio (OR), 1.45 (95% confidence interval [95% CI], 0.86-2.43); 7-day OR, 1.46 (95% CI, 0.80-2.67); and 2-day OR, 2.26 (95% CI, 1.10-4.64). These associations were greater for children aged younger than 2 years and were usually due to the recent administration (preceding 2 days) of antibiotics (OR, 8.00; 95% CI, 1.47-43.7). CONCLUSIONS: Intussusception was more common among boys aged younger than 2 years. A positive and significant association was observed when drugs were administered 2 to 7 days before the onset of symptoms in children younger than the age of 2 years.

Four-food group elimination diet for adult eosinophilic esophagitis: A prospective multicenter study.

BACKGROUND: Eosinophilic esophagitis (EoE) is an esophageal disorder predominantly triggered by food antigens. A six-food group elimination diet (SFGED) achieves remission in more than 70% of adult patients with EoE. After individual food reintroduction, just 1 or 2 food triggers for EoE can be identified in 65% to 85% of the patients, so some dietary restrictions and endoscopies after food challenge may be unnecessary. OBJECTIVE: To evaluate the efficacy of a four-food group elimination diet (FFGED) (dairy products, wheat, egg, and legumes) for adult patients with EoE. METHODS: Prospective multicenter study. All patients were reevaluated after 6 weeks on an FFGED. Response to the FFGED was defined by clinical and histologic (<15 eos/hpf) remission. Responders underwent reintroduction of each individual food over 6 weeks followed by endoscopy and esophageal biopsies. Nonresponders were offered a rescue SFGED. RESULTS: A total of 52 adult patients were included, of whom 12 patients (23%) had previous failure to topical steroid therapy. Twenty-eight of the 52 patients (54%) achieved clinicopathologic remission on the FFGED and 6 of the 19 (31%) nonresponders to the FFGED were successfully rescued with the SFGED. Twenty-two of 28 responders to the FFGED (78%) finished the individual food reintroduction challenge. Milk was identified as an EoE trigger in 11 patients (50%), egg in 8 (36%), wheat in 7 (31%), and legumes in 4 (18%). All patients had just 1 or 2 food triggers, with milk being the only causative food in 27% of the patients. CONCLUSIONS: An FFGED achieved clinicopathologic remission in 54% of adult patients with EoE. An SFGED was effective in almost a third of FFGED nonresponders, resulting in a combined efficacy of 72% of both strategies.

Risk of bleeding in patients undergoing percutaneous endoscopic gastrotrostomy (PEG) tube insertion under antiplatelet therapy: a systematic review with a meta-analysis.

BACKGROUND AND AIM: Patients undergoing percutaneous endoscopic gastrostomy (PEG) tube placement often are under antiplatelet therapy with a potential thromboembolic risk if these medications are discontinued. This systematic review aims to assess if maintaining aspirin and/or clopidogrel treatment increases the risk of bleeding following PEG placement. METHODS: A systematic search of the MEDLINE, EMBASE, and SCOPUS databases was developed for studies investigating the risk of bleeding in patients on antiplatelet therapy undergoing PEG tube insertion. Summary estimates, including 95 % confidence intervals (CI), were calculated. A fixed or random effects model was used depending on heterogeneity (I2). Publication bias risks were assessed by means of funnel plot analysis. RESULTS: Eleven studies with a total of 6,233 patients (among whom 3,665 were undergoing antiplatelet treatment), met the inclusion criteria and were included in the quantitative summary.Any PEG tube placement-related bleeding was found in 2.67 % (95 % CI 1.66 %, 3.91 %) of the entire population and in 2.7 % (95 % CI 1.5 %, 4.1 %) of patients not receiving antiplatelet therapy. Pooled relative risk (RR) for bleeding in patients under aspirin, when compared to controls, was 1.43 (95 % CI 0.89, 2.29; I2 = 0 %); pooled RR for clopidogrel was 1.21 (95 % CI 0.48, 3.04; I2 = 0 %) and for dual antiplatelet therapy, 2.13; (95 % CI 0.77,5.91; I2 = 47 %). No significant publication bias was evident for the different medications analyzed. CONCLUSION: Antiplatelet therapy was safe among patients undergoing PEG tube insertion. Future prospective and randomized studies with larger sample sizes are required to confirm the results of this study.

Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis.

BACKGROUND: The onset of eosinophilic esophagitis (EoE) after oral immunotherapy (OIT) has been repeatedly described in patients with immunoglobulin E (IgE)-mediated food allergy in recent years, but the relation between the 2 conditions has not been fully assessed and quantified. OBJECTIVE: To provide a systematic review of the evidence for an association between OIT and EoE. METHODS: Electronic searches were performed with keywords relating to EoE and OIT in the MEDLINE, EMBASE, and SCOPUS databases. Summary estimates were calculated. A fixed-effects model was used depending on heterogeneity (I(2)). Risk of publication bias was assessed by funnel plot analysis and the Egger test. RESULTS: The search yielded 118 documents, 15 of which were included in the quantitative summary. Most reported information came from children undergoing peanut, milk, and egg OIT. Significant publication bias in favor of studies reporting the development of EoE after OIT was documented. The overall prevalence of EoE after OIT was 2.7% (95% confidence interval 1.7%-4.0%, I(2) = 0%). Differences between medium-to high-quality studies and those of low quality were documented (3.5% vs 2.5%, respectively). EoE often resolved after OIT discontinuation; histologic remission of EoE achieved after allergen immunotherapy also was documented in 2 patients whose topical fluticasone treatment failed. CONCLUSION: New onset of EoE after OIT occurs in up to 2.7% of patients with IgE-mediated food allergy undergoing this treatment strategy. The limited data on the utility of allergen immunotherapy as a therapy for EoE prevent a recommendation for this treatment option.

Treatment of adult eosinophilic esophagitis with diet.

BACKGROUND/AIMS: A growing body of research indicates that dietary therapy is an effective treatment option for children with eosinophilic esophagitis (EoE). Its ability to achieve sustained symptomatic and histological responses is comparable to that of topical steroids, but avoids their use and side effects. Recent studies also support dietary therapy as a preferred treatment option for adult patients. METHODS: A comprehensive literature review was carried out to assess the efficacy of the most commonly used dietary interventions in inducing and maintaining disease remission in adult EoE patients as compared with results from pediatric studies. RESULTS: The only available study assessing exclusive feeding with an elemental diet carried out in adults demonstrated a 94% disease remission rate, comparable to the high efficacy reported in pediatric studies. The major drawbacks of this therapy are poor adherence and a rapid disease recurrence after resumption of a normal diet. Although there is limited data on skin allergy testing-directed food elimination in adult patients, the highest efficacy rates observed do not exceed 26% histological remission. Prospective studies on empirical six-food elimination diets in adults provided efficacy rates comparable to those reported in children, achieving disease remission in approximately 75% of patients. However, specific food triggers can only be identified after documented recurrence of eosinophilic inflammation as determined with repeated endoscopic biopsies. Prolonged avoidance of the offending food(s) produces sustained remission of adult EoE. CONCLUSIONS: Diet is a feasible therapeutic option for adult EoE patients, providing them with the same effective drug-free alternative as in pediatric patients.