NOD2 and Crohn's Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a multifactorial pathogenesis involving environmental and genetic factors. Since the late 20th century, the discovery of the first susceptibility gene (NOD2, previously referred to as CARD15) for CD has paved the way for further investigations into the correlations between clinical features and genetics, and its potential impact on clinical practice has fueled the research in the last 2 decades. Recent therapeutic advancements involving novel biologic drugs and small molecules have shifted inflammatory bowel disease management from a disease-centered to a patient-centric approach. To date, the role of NOD2 has not been fully understood yet. Recent data suggest that its clinical impact may be greater than currently recognized. This review overviews the most common NOD2 variants' role in real-life clinical practice. These genetic variants increase the risk of developing the disease and can aid in tailoring diagnosis and treatment. They are associated with the stricturing phenotype and ileal involvement and increase the risk of steroid refractoriness. In the meantime, limited and inconclusive evidence exists regarding their predictive role in response to azathioprine, biologic drugs, and small molecules. Eventually, their role in increasing the risk for surgery is evident, especially in those with the L1007fs variant. If further trials will support the initial evidence reported so far, NOD2 genetic variants will emerge as possible candidates for developing precision medicine in CD.

NOD2 is the most relevant susceptibility gene for Crohn's disease. It is associated with the tructuring disease phenotype, ileal involvement, and an increased risk for surgery. NOD2 genetic variants emerge as promising candidates for developing precision medicine in Crohn's disease.

Lowest Case Fatality Rate for Patients With Acute Pancreatitis Admitted in Gastroenterology Units in Veneto Region, Italy.

OBJECTIVES: This study aimed to evaluate trends in hospitalizations and outcomes of acute pancreatitis (AP) according to first admitting hospital unit and hospital volumes. METHODS: Hospital discharge records of patients with AP admitted in the Veneto Region (Northeast Italy) during the period 2001-2015 were examined. RESULTS: A total of 23,389 patients (54% males; mean age, 62.2 years; standard deviation, 19.3 years) were admitted for AP. Both hospitalization (32.4 to 29.5/100,000 inhabitants per year; P < 0.05) and in-hospital mortality (1.41 to 0.79/100,000 inhabitants per year; P < 0.05) decreased over the study period. Case fatality rate was altogether 3.2%. The percentages of patients admitted in surgery, nongastroenterology medical units, gastroenterology, and intensive care were 52%, 30%, 16%, and 2%, respectively. Fewer fatalities were observed in gastroenterology units (1.7%) compared with nongastroenterology medical units (4.3%; odds ratio, 0.37; 95% confidence interval, 0.28-0.49) and surgical units (2.7%; odds ratio, 0.61; 95% confidence interval, 0.47-0.80). Fatalities decreased progressively with increasing hospital volumes from 3.7% to 2.9% (P < 0.05). CONCLUSION: In the Veneto Region, both hospitalizations and in-hospital mortality for AP significantly decreased over the last 15 years. Case fatality rate was lowest for patients admitted in gastroenterology units.

Usefulness of a serological panel test in the assessment of gastritis in symptomatic children.

BACKGROUND: Non-invasive methods are advisable for the detection of Helicobacter pylori-related chronic gastritis in pediatric patients. Serum pepsinogens I and II (sPGII and sPGII), gastrin-17 (G-17) and anti-H. pylori antibodies (IgG-Hp) have been proposed as a 'serological gastric biopsy'. AIM: To assess H. pylori infection and to evaluate gastric mucosa status in a pediatric population by means of serological parameters such as sPGI, sPGII, G-17 and IgG-Hp. METHODS: 45 consecutively children evaluated for upper gastrointestinal symptoms were analyzed. All children were submitted to upper gastrointestinal endoscopy with biopsies. Serum samples were analyzed for IgG-Hp, sPGII, sPGI and G-17 (Biohit, Helsinki, Finland). RESULTS: 18 children had H. pylori-related mild or moderate non-atrophic chronic gastritis. They presented significantly higher mean levels of sPGII and of IgG-Hp than negative ones, either under or up to 10 years. sPGI showed significantly increased levels in H. pylori-positive patients only over 10 years. G-17 levels were not different between H. pylori-positive and -negative ones. The best cut-offs of IgG-Hp, sPGII and of product IgG-Hp x sPGII, to identify H. pylori infection, were 30 IU/l, 9 microg/l, and 241 IU/l x microg/l, respectively. The product IgG-Hp x sPGII identified H. pylori infection with a 100% sensitivity, 92% specificity, 90% positive predictive value and 100% negative predictive value. IgG-Hp and IgG-Hp showed a correlation (r = 0.94; p < 0.001). CONCLUSIONS: Combined analysis of sPGII and IgG-Hp antibody levels could be recommended as a non-invasive panel for the assessment of H. pylori-related histological alterations of gastric mucosa in childhood.

Effects of chronic therapy with non-steroidal antiinflammatory drugs on gastric permeability of sucrose: a study on 71 patients with rheumatoid arthritis.

AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This technique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.

Does Helicobacter pylori infection eradication modify peptic ulcer prevalence? A 10 years' endoscopical survey.

AIM: To compare peptic ulcer prevalence in patients referred for upper gastrointestinal endoscopy in two Italian hospitals in pre-Helicobacter era and ten years after the progressive diffusion of eradication therapy. METHODS: We checked all the endoscopic examinations consecutively performed in the Gastroenterology Unit of Padova during 1986-1987 and 1995-1996, and in the Gastroenterology Unit of Parma during 1992 and 2002. Chi Square test was used for statistic analysis. RESULTS: Data from both the endoscopic centers showed a statistically significant decrease in the prevalence of ulcers: from 12.7% to 6.3% (P<0.001) in Padova and from 15.6% to 12% (P<0.001) in Parma. The decrease was significant both for duodenal (from 8.8% to 4.8%, P<0.001) and gastric ulcer (3.9% to 1.5%, P<0.001) in Padova, and only for duodenal ulcer in Parma (9.2% to 6.1%, P<0.001; gastric ulcer: 6.3% to 5.8%, NS). CONCLUSION: Ten years of extensive Helicobacter pylori (H pylori) eradication in symptomatic patients led to a significant reduction in peptic ulcer prevalence. This reduction was particularly evident in Padova, where a project for the sensibilization of H pylori eradication among general practioners was carried out between 1990 and 1992. Should our hypothesis be true, H pylori eradication might in the future lead to peptic ulcer as a rare endoscopic finding.

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = -0.33, P < .001) and intestinal metaplasia (r = -0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

Influence of antisecretory treatment with proton pump inhibitors on serum pepsinogen I levels.

It has been reported in literature that serum pepsinogen levels rise during omeprazole and lansoprazole administration. However, the influence of pantoprazole and esomeprazole on serum pepsinogens levels is still to be assessed. The aim of this study was to evaluate the influence of proton pump inhibitor (PPI) therapy on pepsinogen I (PGI) levels. PGI and gastrin (G17) levels (EIA; Biohit, Helsinki, Finland) in 126 consecutive patients (M 57; F 69, mean age 53, range 15-91), with upper gastrointestinal symptoms at baseline condition and after 2 months of PPI treatment, were evaluated. Patients underwent a therapy schedule based on: omeprazole 20 mg b.i.d. (20 patients), pantoprazole 40 mg b.i.d. (27 patients), esomeprazole 40 mg b.i.d. (29 patients), lansoprazole 30 mg b.i.d. (21 patients) and rabeprazole 20 mg b.i.d. (26 patients) for 2 months. A significant increase in serum PGI (sPGI) levels was found after a 2-month treatment for all five different PPIs: omeprazole, pantoprazole, esomeprazole, lansoprazole and rabeprazole (P < 0.05). The effect of rabeprazole on sPGI was less pronounced as compared with other PPIs, whereas esomeprazole achieved superior sPGI levels, with no overall statistically significant difference among the five groups (P > 0.05). However, a comparison within a single group of PPIs showed a statistical significance when the esomeprazole group was compared with the rabeprazole group (P = 0.007). sPGI levels are significantly influenced by antisecretory therapy, rising under PPI treatment. Moreover, a statistically significant difference in sPGI levels between the rabeprazole and esomeprazole groups has been demonstrated.

Natural course of functional dyspepsia after Helicobacter pylori eradication: a seven-year survey.

The role of Helicobacter pylori(Hp) in functional dyspepsia (FD) is controversial and previously published data do not help to clarify whether Hp eradication affects the natural course of FD. The aim of this study was to assess the clinical course of FD during a long follow-up period of 7 years in a homogeneous sample of Hp-eradicated patients. Among patients referred between 1991 and 1996, patients with FD and infected with Hp were enrolled. Patients were administered a structured symptom questionnaire and evaluated after Hp eradication at each 12-month time points. Patients were divided into three FD subgroups: predominantly ulcer-like, dismotility-like, and reflux-like symptom clusters. A composite symptom score ranging from 0 (no symptom) to 3 (severe symptoms) was assigned to each FD cluster. Of the 1685 screened patients, 405 had FD and 211 of them (52.1%) were also Hp-positive. During the follow-up, the amount of missing information varied from 10% to 17.5% within the first 6 years and was 30.8% at 7 years. The rates of improved patients ranged from 33% (reflux-like) to 34.9% (dismotility-like) to 47.3% (ulcer-like). However, only a proportion of 10%-50% of them was symptom-free after eradication and also at each 12-month evaluation, whereas the other patients became symptomatic at different times. FD symptoms slightly improve after Hp eradication over a long period of time but a large percentage of these improved patients may experience FD symptoms again, even after some years of well-being after Hp eradication.

Clinical usefulness of serum pepsinogen II in the management of Helicobacter pylori infection.

BACKGROUND: Serum pepsinogen II (sPGII) levels are known to increase during Helicobacter pylori infection. AIM: To assess H. pylori infection and success of H. pylori therapy by means of sPGII levels. METHODS: sPGII levels were determined in 156 H. pylori-positive and 157 H. pylori-negative consecutive patients with dyspeptic symptoms. Additionally, sPGII determination was performed in 70 H. pylori-positive patients 2 months after H. pylori eradication therapy. In 29 of these 70 patients, gastroscopy was performed to evaluate the effect of H. pylori therapy on gastric activity. RESULTS: H. pylori-positive subjects demonstrated a significantly higher mean of sPGII levels than H. pylori-negative subjects (16.8 +/- 7.4 vs. 8.6 +/- 3.7 microg/l; p < 0.001). The best sPGII cut-off for predicting H. pylori infection was 9.93 microg/l (sensitivity 83%, specificity 73%). The best cut-off values to evaluate success of therapy were: sPGII of 9.47 microg/l, a sPGII variation level (difference between baseline and after therapy) of 4.54 microg/l, and a sPGII Deltavalue (sPGII variation divided by sPGII before therapy) of 25% (sensitivity 93%, specificity 91%). CONCLUSIONS: sPGII levels may be used as a reliable marker of H. pylori infection in the initial diagnosis as well as to evaluate H. pylori eradication and subsequent changes in gastric inflammation.