Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

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.

Attending Training Courses on Barrett's Esophagus Improves Adherence to Guidelines: A Survey from the Italian Society of Digestive Endoscopy.

BACKGROUND: Little is known on practice patterns of endoscopists for the management of Barrett's esophagus (BE) over the last decade. AIMS: Our aim was to assess practice patterns of endoscopists for the diagnosis, surveillance and treatment of BE. METHODS: All members of the Italian Society of Digestive Endoscopy (SIED) were invited to participate to a questionnaire-based survey. The questionnaire included questions on demographic and professional characteristics, and on diagnosis and management strategies for BE. RESULTS: Of the 883 SIED members, 259 (31.1%) completed the questionnaire. Of these, 73% were males, 42.9% had > 50 years of age and 68.7% practiced in community hospitals. The majority (82.9%) of participants stated to use the Prague classification; however 34.5% did not use the top of gastric folds to identify the gastro-esophageal junction (GEJ); only 51.4% used advanced endoscopy imaging routinely. Almost all respondents practiced endoscopic surveillance for non-dysplastic BE, but 43.7% performed eradication in selected cases and 30% practiced surveillance every 1-2 years. The majority of endoscopists managed low-grade dysplasia with surveillance (79.1%) and high-grade dysplasia with ablation (77.1%). Attending a training course on BE in the previous 5 years was significantly associated with the use of the Prague classification (OR 4.8, 95% CI 1.9-12.1), the top of gastric folds as landmark for the GEJ (OR 2.45, 95% CI 1.27-4.74) and advanced imaging endoscopic techniques (OR 3.33, 95% CI 1.53-7.29). CONCLUSIONS: Practice patterns for management of BE among endoscopists are variable. Attending training courses on BE improves adherence to guidelines.

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.

Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome.

BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10-8) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10-6). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10-10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.

OBJECTIVE: IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. DESIGN: We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. RESULTS: CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). CONCLUSIONS: SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients.

Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).

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.

Randomised controlled trial of mesalazine in IBS.

OBJECTIVE: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER: ClincialTrials.gov number, NCT00626288.

Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.

BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules.

AIM: Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. BACKGROUND: Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. METHODS: Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. RESULTS: Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. CONCLUSION: Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Hypoxic Functional Regulation Pathways in the GI Tract: Focus on the HIF-1α and Microbiota's Crosstalk.

Hypoxia is an essential gastrointestinal (GI) tract phenomenon that influences both physiologic and pathologic states. Hypoxia-inducible factors (HIFs), the primary drivers of cell adaptation to low-oxygen environments, have been identified as critical regulators of gut homeostasis: directly, through the induction of different proteins linked to intestinal barrier stabilization (ie, adherent proteins, tight junctions, mucins, integrins, intestinal trefoil factor, and adenosine); and indirectly, through the regulation of several immune cell types and the modulation of autophagy and inflammatory processes. Furthermore, hypoxia and HIF-related sensing pathways influence the delicate relationship existing between bacteria and mammalian host cells. In turn, gut commensals establish and maintain the physiologic hypoxia of the GI tract and HIF-α expression. Based on this premise, the goals of this review are to (1) highlight hypoxic molecular pathways in the GI tract, both in physiologic and pathophysiologic settings, such as inflammatory bowel disease; and (2) discuss a potential strategy for ameliorating gut-related disorders, by targeting HIF signaling, which can alleviate inflammatory processes, restore autophagy correct mechanisms, and benefit the host-microbiota equilibrium.

In recent years, hypoxic conditions, with subsequent hypoxia-inducible factor activation, and the gut's microbiota composition have both received significant attention due to their correlation with gut homeostasis maintenance. However, their potential synergic action needs further investigation.

Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

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.

An Italian prospective multicenter study on colonoscopy practice and quality: What has changed in the last 10 years.

BACKGROUND: A relevant number of adenomas can be missed during colonoscopy. AIMS: Assess the current status of colonoscopy procedures in Italian centers. METHODS: A prospective observational study involving 17 hospitals (34 endoscopists) included consecutive patients undergoing standard colonoscopy. In the first phase, endoscopists performed consecutive colonoscopies. In the second phase, retraining via an online learning platform was planned, while in the third phase data were collected analogously to phase 1. RESULTS: A total of 3,504 patients were enrolled. Overall, a BBPS score ≥6 was obtained in 95.6% of cases (94.8% and 96.9% in the pre- and post-training phases, respectively). 88.4% of colonoscopies had a withdrawal time ≥6 min (88.2% and 88.7% in the pre- and post-training phases). Median adenoma detection rate (ADR) was 39.1%, with no significant differences between the pre- and post-training phases (40.1% vs 36.9%; P = 0.83). In total, 81% of endoscopists had a ADR performance above the 25% threshold. CONCLUSION: High colonoscopy quality standards are achieved by the Italian hospitals involved. Quality improvement initiatives and repeated module-based colonoscopy-training have been promoted in Italy during the last decade, which appear to have had a significant impact on quality colonoscopy metrics together with the activation of colorectal cancer screening programs.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

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.

Obscure and occult gastrointestinal bleeding: comparison of different imaging modalities.

Patients with persistent, recurrent, or intermittent bleeding from the gastrointestinal (GI) tract for which no definite cause has been identified by initial esophagogastroduodenoscopy, colonoscopy, or conventional radiologic evaluation are considered to have an obscure GI bleeding (OGIB). The diagnosis and management of patients with OGIB is challenging, often requiring extensive and expensive workups. The main objective is the identification of the etiology and site of bleeding, which should be as rapidly accomplished as possible, in order to establish the most appropriate therapy. The introduction of capsule endoscopy and double balloon enteroscopy and the recent improvements in CT and MRI techniques have revolutionized the approach to patients with OGIB, allowing the visualization of the entire GI tract, particularly the small bowel, until now considered as the "dark continent" . In this article we review and compare the radiologic and endoscopic examinations currently used in occult and OGIB, focusing on diagnostic patterns, pitfalls, strengths, weaknesses, and value in patients' management.

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.