Upper Gastrointestinal Endoscopy Quality in Italy: A Nationwide Study.

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.

Gene Expression Profiling in Coeliac Disease Confirmed the Key Role of the Immune System and Revealed a Molecular Overlap with Non-Celiac Gluten Sensitivity.

Coeliac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten and an as yet unidentified environmental factor in genetically predisposed individuals. The disease involves a major autoimmune component that primarily damages the intestinal mucosa; although, it also has systemic involvement. The Th1 inflammatory response is one of the main events leading to mucosal damage; although, enterocytes and the innate immune response also participate in the pathological mechanism. In this study, we performed an analysis of the gene expression profile of the intestinal mucosa of patients with active disease and compared it with that of patients who do not suffer from gluten-related disorders but report dyspeptic symptoms. This analysis identified 1781 differentially expressed (DE) genes, of which 872 were downregulated and 909 upregulated. Gene Ontology and pathway analysis indicated that the innate and adaptive immune response, in particular the Th1 pathway, are important pathogenetic mechanisms of CeD, while the key cytokines are IL27, IL21, IL2, IL1b, TNF, CSF2 and IL7, as well as type I (IFNA1, IFNA2) and type II (IFNG) interferons. Finally, the comparison between the DE genes identified in this study and those identified in our previous study in the intestinal mucosa of patients with non-celiac gluten sensitivity (NCGS) revealed a high degree of molecular overlap. About 30% of the genes dysregulated in NCGS, most of which are long non-coding RNAs, are also altered in CeD suggesting that these diseases may have a common root (dysregulated long non-coding RNAs) from which they develop towards an inflammatory phenotype of variable degree in the case of CeD and NCGS respectively.

Has the COVID-19 Pandemic Worsened Health-Related Quality of Life of Patients with Inflammatory Bowel Disease? A Longitudinal Disease Activity-Controlled Study.

The present longitudinal study aimed to investigate the burden of disease activity change on health-related quality of life (HRQoL) of patients with inflammatory bowel disease (IBD) during the two different pandemic waves in 2020 and 2021. A sample of 221 IBD patients (recruited during March-May 2020 for T0 and March-May 2021 for T1) was included. The psychological impact of the COVID-19 pandemic (Impact of Event Scale-Revised (IES-R)) and HRQoL (Inflammatory Bowel Disease Questionnaire (IBDQ)) were assessed. Post-traumatic COVID-19-related symptoms (IES-R) were not significantly different across the disease activity-related groups. Conversely, IBDQ was consistently higher in patients with persistent, quiescent disease activity compared to the other groups, as expected. Even after controlling for baseline IES-R, repeated-measures ANCOVA showed a non-significant main effect of time (p = 0.60) but a significant time-per-group interaction effect with a moderate effect size (η2 = 0.08). During the two different phases of pandemic restrictions, IBD-specific HRQoL was modified by disease-related factors such as disease activity, rather than by the post-traumatic symptoms of COVID-19. This lends further weight to the need for developing an evidence-based, integrated, biopsychosocial model of care for patients with IBD to identify subjective and objective factors that affect the burden of disease.

Diagnostic delay in adult coeliac disease: An Italian multicentre study.

BACKGROUND: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD). AIMS: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD. METHODS: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted. RESULTS: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay. CONCLUSION: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented.

Gastrointestinal manifestations of SARS-CoV-2 infection in an Italian population of hospitalized patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters the cells via angiotensin-converting enzyme 2 receptor; therefore, tissues expressing this receptor are potential targets for infection. Although many studies have observed gastrointestinal (GI) symptoms in coronavirus disease 2019 (COVID-19) patients, prevalence and clinical impact are still uncertain due to the heterogeneity of reports and obstacles to generalization. Methods: In this cross-sectional study, we included symptomatic patients requiring hospital admission, with a confirmed diagnosis of COVID-19 by nasopharyngeal polymerase chain reaction test, between 18 March and 30 May 2020. Demographic data, symptoms at onset, vital signs, and laboratory tests at admission were recorded. Results: In all, 300 patients were included (57%M, 43%F). GI symptoms were mainly diarrhea (13%), anorexia (4.3%), vomiting (3%), and abdominal pain (2.3%). Overall, males were younger (68 years versus 76 years; p = 0.01); patients with GI manifestations at disease onset required significantly faster hospital admission and showed larger GI complication rates. GI symptoms were associated with abnormal high aspartate aminotransferase and alanine aminotransferase serum titers, especially in male patients. Conclusion: Our study on an Italian population during the outbreak of the COVID-19 pandemic shows that GI symptoms are part of the spectrum of the SARS-CoV-2 infection and could be the only manifestations at disease onset. Although patients with GI symptoms were associated with faster hospital admission and liver involvement, prognosis was not affected.

The role of Zinc L-Carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review.

Zinc L-carnosine is a pharmaceutical compound with direct mucosal cytoprotective and anti-inflammatory action through its antioxidative effects, cytokine modulation and membrane-stabilizing properties. Chemically, it is not an anti-secretory, antacid or raft-forming agent; its properties are mainly mediated by its higher affinity for damaged mucosa that permits the release of zinc locally by ligand exchange. Beneficial effects on various types of mucosal damage have been described in vitro and in vivo, in both animals and humans. It has been shown to promote repair of mucosal injury in human studies and has been widely used for the treatment of peptic ulcers, chemoradiotherapy-induced oral mucositis and esophagitis. More recently, the therapeutic applications of Zinc L-carnosine have been extended to the prevention and cure of various types of intestinal damage, including ulcerative colitis, iatrogenic ulcers after operative endoscopy, hemorrhoidal disease and impaired intestinal permeability. This review concentrates mainly on the current and future applications of zinc L-carnosine in gastrointestinal disease, and may be of use to gastroenterologists and endoscopists. It describes the therapeutic principles and benefits of this interesting molecule and discusses the potential future fields of interest for clinical use in humans.

Circulating Extracellular Vesicles Are Increased in Newly Diagnosed Celiac Disease Patients.

Extracellular vesicles (EVs) are a class of circulating entities that are involved in intercellular crosstalk mechanisms, participating in homeostasis maintenance, and diseases. Celiac disease is a gluten-triggered immune-mediated disorder, characterized by the inflammatory insult of the enteric mucosa following local lymphocytic infiltration, resulting in villous atrophy. The goal of this research was the assessment and characterization of circulating EVs in celiac disease patients, as well as in patients already on an adequate gluten-free regimen (GFD). For this purpose, a novel and validated technique based on polychromatic flow cytometry that allowed the identification and enumeration of different EV sub-phenotypes was applied. The analysis evidenced that the total, annexin V+, leukocyte (CD45+), and platelet (CD41a+) EV counts were significantly higher in both newly diagnosed celiac disease patients and patients under GFD compared with the healthy controls. Endothelial-derived (CD31+) and epithelial-derived (EpCAM+) EV counts were significantly lower in subjects under gluten exclusion than in celiac disease patients, although EpCAM+ EVs maintained higher counts than healthy subjects. The numbers of EpCAM+ EVs were a statistically significant predictor of intraepithelial leukocytes (IEL). These data demonstrate that EVs could represent novel and potentially powerful disease-specific biomarkers in the context of celiac disease.

Effect of Third-Generation Beta Blockers on Weight Loss in a Population of Overweight-Obese Subjects in a Controlled Dietary Regimen.

BACKGROUND: Overweight and obesity often develop in individuals with genetic susceptibility and concomitant risk factors; however, medications can represent precipitating factors in some cases: evidence suggests that some antihypertensive drugs can adversely affect energy homeostasis and metabolism. AIM: The primary aim of this study was to investigate whether long-term therapy with a beta blocker impairs weight loss during a period of appropriate personalized hypocaloric diet and standardized physical activity in overweight and obese hypertensive patients in monotherapy and without comorbidities, compared to other antihypertensive drugs and to a control group not taking antihypertensive therapy. Subjects and Methods. We enrolled overweight and obese patients taking antihypertensive drugs; subjects were divided into 3 groups: those taking traditional beta blockers (bB group), those taking third-generation beta blockers (bB-3 group), and those taking other antihypertensive drugs (non-bB group). We also enrolled subjects receiving neither antihypertensive therapy nor other chronic medication in the prior 12 months as controls. All subjects underwent personalized hypocaloric diets for a period of 24 months with monthly follow-up. Anthropometric parameters were measured at enrollment and then monthly after diet prescription. Glucose and lipid values were assessed at baseline and at 12 and 24 months during dietary regimen. RESULTS: We enrolled a total of 120 overweight and obese patients aged 50.30 ± 1.13 years (mean ± standard deviation) with a mean BMI of 31.79 ± 0.65 kg/m2; 90 were taking antihypertensive drugs (no comorbidity and no polytherapy), while 30 subjects receiving neither antihypertensive therapy nor other chronic medication in the prior 12 months were considered as controls. After 6 months, the percent total weight loss (TWL%) was lower in the bB group (3.62 ± 1.96 versus 5.27 ± 1.76 in the bB-3 group, versus 5.15 ± 1.30 in the non-bB group, and versus 4.70 ± 0.87 in the control group), as well as their BMI. After 24 months, we kept finding the worst result in the bB group (TWL% = 9.22 ± 2.19 versus 12.79 ± 1.72 in the non-bB group and 12.28 ± 1.97 in the control group) with the best trend in the bB-3 group (TWL% = 16.19 ± 2.67).

Influence of the COVID-19 Outbreak on Disease Activity and Quality of Life in Inflammatory Bowel Disease Patients.

Objective: The present preliminary cross-sectional study aimed to investigate the extent to which health-related quality of life of patients with inflammatory bowel disease (IBD) was influenced by the outbreak of Covid-19 while controlling for disease activity. Methods: Two samples of 195 (recruited before Covid-19 outbreak) and 707 patients (recruited during the Covid-19-related lockdown) were included. Psychological distress (Hospital Anxiety and Depression Scale, HADS), quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), and somatization (Patient Health Questionnaire, PHQ-12) were concurrently assessed. Results: Patients with active IBD were more prevalently affected by ulcerative colitis (60.2%, η2 = 0.12) and, expectedly, showed higher psychological distress (HADS, d = 0.34) and somatization (PHQ-12, d = 0.39), as well as poorer disease-specific health-related quality of life (effect sizes for the total and subscale IBDQ scores in the large range of d > 0.50). Hierarchical regression models revealed that setting (pre-Covid-19 outbreak vs. during lockdown) (p < 0.001) explained only a small portion (8%) of the IBDQ variance. IBD-related factors (ulcerative colitis and disease activity) and psychological factors (psychological distress and somatization) added a significant amount of 25 and 27%, respectively, to the explained IBDQ variance. The final model predicted 59% of the explained IBDQ variance. Conclusion: Clinical and psychological manifestations seem to be major impairments in IBD patients both before and during the Covid-19 outbreak. Furthermore, the quality of life of IBD patients seem to be more influenced by psychological and somatizing distressing symptoms than the pandemic-related living conditions.

Beyond the HLA Genes in Gluten-Related Disorders.

Most common food grains contain gluten proteins and can cause adverse medical conditions generally known as gluten-related disorders. Celiac disease is an immune-mediated enteropathy triggered by gluten in individuals carrying a specific genetic make-up. The presence of the human leukocyte antigens (HLA)-DQ2 and HLA-DQ8 haplotypes together with gluten intake is a necessary, although not sufficient, condition, to develop celiac disease. Fine mapping of the human genome has revealed numerous genetic variants important in the development of this disease. Most of the genetic variants are small nucleotide polymorphisms located within promoters and transcriptional enhancer sequences. Their importance is underlined by an increased risk in DQ2/DQ8 carriers who also have these non-HLA alleles. In addition, several immune-mediated diseases share susceptibility loci with celiac disease, shedding light on the reasons for co-occurrence between these diseases. Finally, most of the genes potentially involved in celiac disease by fine genetic mapping of non-HLA loci were confirmed in gene expression studies. In contrast to celiac disease, very little is known about the genetic make-up of non-celiac wheat sensitivity (NCWS), a clinically defined pathology that shares symptoms and gluten dependence with the celiac disease. We recently identified differentially expressed genes and miRNAs in the intestinal mucosa of these patients. Remarkably, the differentially expressed genes were long non-coding RNAs possibly involved in the regulation of cell functions. Thus, we can speculate that important aspects of these diseases depend on alteration of regulatory genetic circuits. Furthermore, our finding suggests that innate immune response is involved in the pathogenic mechanism of NCWS. This review is intended to convey the idea that in order to fully understand celiac disease and its relationship with other gluten-related disorders, it is worth learning more about non-HLA variants.

An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity.

Non-celiac wheat sensitivity (NCWS) is a recently recognized syndrome triggered by a gluten-containing diet. The pathophysiological mechanisms engaged in NCWS are poorly understood and, in the absence of laboratory markers, the diagnosis relies only on a double-blind protocol of symptoms evaluation during a gluten challenge. We aimed to shed light on the molecular mechanisms governing this disorder and identify biomarkers helpful to the diagnosis. By a genome-wide transcriptomic analysis, we investigated gene expression profiles of the intestinal mucosa of 12 NCWS patients, as well as 7 controls. We identified 300 RNA transcripts whose expression differed between NCWS patients and controls. Only 37% of these transcripts were protein-coding RNA, whereas the remaining were non-coding RNA. Principal component analysis (PCA) and receiver operating characteristic curves showed that these microarray data are potentially useful to set apart NCWS from controls. Literature and network analyses indicated a possible implication/dysregulation of innate immune response, hedgehog pathway, and circadian rhythm in NCWS. This exploratory study indicates that NCWS can be genetically defined and gene expression profiling might be a suitable tool to support the diagnosis. The dysregulated genes suggest that NCWS may result from a deranged immune response. Furthermore, non-coding RNA might play an important role in the pathogenesis of NCWS.

An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity.

Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.

Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria.

BACKGROUND: Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of 'harmonized' criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population. METHODS: In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 'harmonized' criteria. RESULTS: Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54-2.00] and cancer (OR: 1.92, 95% CI 1.42-2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated. CONCLUSIONS: MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.

Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease.

BACKGROUND: The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing. AIMS: To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated. METHODS: Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring. RESULTS: Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group. CONCLUSIONS: True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group.

Impact of chocolate on the cardiovascular health.

The antioxidants such as polyphenols, especially flavonols, present in large quantitites in cocoa, cause vasodilation, modulate inflammatory markers and cardiovascular health, and possess a range of protective cardiovascular effects. On the other hand, overconsumption of chocolate can lead to tachyarrhythmias, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and ventricular fibrillation due to its caffeine content. This review describes both the cardioprotective and adverse effects of chocolate and its constituents.

Application of the Biopsy-Sparing ESPGHAN Guidelines for Celiac Disease Diagnosis in Adults: A Real-Life Study.

BACKGROUND: Current adult celiac disease diagnosis requires histological confirmation. However, pediatric guidelines have proposed biopsy-sparing algorithms. AIMS: To explore the applicability of the ESPGHAN criteria and assess the accuracy of serology in predicting disease in adults. METHODS: We evaluated 234 consecutive adults showing elevated anti-tTG titers, EMA-positivity, and genetic susceptibility. Patients underwent upper endoscopy with duodenal biopsy. We determined optimal anti-tTG cutoff levels using ROC curves. RESULTS: Mean anti-tTG levels were 71.1 ± 66.5 U/ml; mean normalized levels were 14.8 ± 14.1 × ULN (mean ± SD). Partial/total villous atrophy was present in 36%/55% of cases, respectively. Anti-tTG levels correlated with histology (r s = 0.397, p < 0.001). AUC was similar before and after normalization (0.803 vs 0.807). Applying the ESPGHAN criterion (≥10 × ULN), we calculated a 97.66% PPV. ROC curve analysis showed an optimal cutoff of ≥16 × ULN, with a PPV of 98.86%. Eleven different assays were used for anti-tTG titer determination: Two were prevalent, labeled A (n = 141) and B (n = 59). They performed differently regarding disease prediction (AUC = 0.689 vs 0.925, p < 0.01), showing distinct optimal cutoff values (14.3 × ULN vs 3.7 × ULN), even after standardization (-0.14 vs -1.2). CONCLUSION: In adult symptomatic patients showing EMA-positivity and genetic susceptibility, anti-tTG titers correlated with histology. ESPGHAN criteria performed similarly to previous studies. However, a calculated 16 × ULN cutoff showed an improved PPV. Among prevalent assays, PPV peaked differently both after normalization and standardization, indicating intrinsic differences in performance, thus preventing uniform prediction of disease in a real-life setting. Assay-specific optimal cutoffs seem possible, but would complicate diagnostic criteria. However, biopsy-sparing strategies in adults could prove useful in challenging patients.

Iron deficiency anemia despite effective gluten-free diet in celiac disease: Diagnostic role of small bowel capsule endoscopy.

BACKGROUND & AIM: Iron deficiency anemia (IDA) is associated with celiac disease (CD). Although gluten-free diet (GFD) is an efficient treatment for CD, IDA remains an occasional finding during follow-up and correlates to inadequate gluten exclusion. Little is known regarding persistent IDA despite effective GFD. We aimed to evaluate the role of small bowel capsule endoscopy (SBCE) in this setting. METHODS: We prospectively included consecutive patients undergoing GFD for ≥24 months with persistent concomitant IDA. Patients were assessed serologically and, if negative, underwent endoscopic evaluation. RESULTS: Twenty-six patients underwent esophago-gastro-duodenoscopy (EGD), colonoscopy and SBCE. Altogether, 11 patients resulted positive. EGD showed mucosal lesions in 7: erosive gastritis (n=3), erosive duodenitis (n=1), active CD (n=3). Colonoscopy showed hemorrhoids in 2. SBCE was positive in 6 cases: erosive jejunitis (n=3, 1 eventually diagnosed as refractory CD, 2 as Crohn's disease), angiodysplasias (n=2), lymphangectasia (n=1). Some overlap was observed between procedures, since in 4 subjects EGD and SBCE produced significant findings. However, in 3 cases SBCE documented severe disease, not found at EGD. Hypoalbuminemia was significantly associated with a positive SBCE outcome (p<0.01). CONCLUSION: SBCE yielded significant findings in 23% of celiacs with persistent IDA despite adequate GFD. These were associated to hypoalbuminemia, indicating their occurrence at more severe stages of the disease.