Effectiveness of first and second-line empirical treatment in Italy: Results of the European registry on Helicobacter pylori management.

BACKGROUND AND AIMS: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg). METHODS: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance. RESULTS: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events. CONCLUSIONS: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment.

Antimicrobial Efficacy of Five Probiotic Strains Against Helicobacter pylori.

Treatment of Helicobacter pylori (H. pylori) infection is a challenge for clinicians. The large increase in drug-resistant strains makes the formulation of new therapeutic strategies fundamental. The frequent onset of side effects during antibiotic treatment (mainly due to intestinal dysbiosis) should not be underestimated as it may cause the interruption of treatment, failure of H. pylori eradication and clonal selection of resistant bacteria. Probiotic integration during antibiotic treatment can exert a dual function: a direct antagonistic effect on H. pylori and a balancing effect on dysbiosis. Therefore, it fulfills the definition of a new therapeutic strategy to successfully treat H. pylori infection. Data reported in literature give promising but discrepant results. AIM: To assess in vitro bacteriostatic and bactericidal activity of probiotic strains against H. pylori. MATERIALS AND METHODS: L. casei, L. paracasei, L. acidophilus, B. lactis and S. thermophilus strains were used. Agar well diffusion and time-kill curves were carried out to detect bacteriostatic and bactericidal activity, respectively. RESULTS: All probiotic strains showed both bacteriostatic and bactericidal activity vs. H. pylori. CONCLUSIONS: Such findings prompted us to plan a protocol of treatment in which probiotics are given to infected patients in association with antibiotic therapy.

Power of screening tests for colorectal cancer enhanced by high levels of M2-PK in addition to FOBT.

Colorectal cancer (CRC) is a multistep process that involves adenoma-carcinoma sequence. CRC can be prevented by routine screening, which can detect precancerous lesions. The aim of this study is to clarify whether faecal occult blood test (i-FOBT), tumor M2 pyruvate kinase (t-M2-PK), and endocannabinoid system molecules (cannabinoid receptors type 1-CB1, type 2-CB2, and fatty acid amide hydrolase-FAAH) might represent better diagnostic tools, alone or in combination, for an early diagnosis of CRC. An immunochemical FOB test (i-FOBT) and quantitative ELISA stool test for t-M2-PK were performed in 127 consecutive patients during a 12 month period. Endocannabinoid system molecules and t-M2-PK expression were detected by immunostaining in healthy tissues and normal mucosa surrounding adenomatous and cancerous colon lesions. i-FOBT and t-M2-PK combination leads to a better diagnostic accuracy for pre-neoplastic and neoplastic colon lesions. T-M2-PK quantification in stool samples and in biopsy samples (immunostaining) correlates with tumourigenesis stages. CB1 and CB2 are well expressed in healthy tissues, and their expression decreases in the presence of advanced stages of carcinogenesis and disappears in CRC. FAAH signal is well expressed in normal mucosa and low-risk adenoma, and increased in high-risk adenoma and carcinoma adjacent tissues. This study shows that high levels of t-M2-PK in addition to FOBT enhance the power of a CRC screening test. Endocannabinoid system molecule expression correlates with colon carcinogenesis stages. Developing future faecal tests for their quantification must be undertaken to obtain a more accurate early non-invasive diagnosis for CRC.

Neighborhood-level social processes and substantiated cases of child maltreatment.

Child maltreatment is a preventable public health problem. Research has demonstrated that neighborhood structural factors (e.g. poverty, crime) can influence the proportion of a neighborhood's children who are victims of maltreatment. A newer strategy is the identification of potentially modifiable social processes at the neighborhood level that can also influence maltreatment. Toward this end, this study examines neighborhood-level data (maltreatment cases substantiated by Illinois' child protection agency, 1995-2005, social processes measured by the Project on Human Development in Chicago Neighborhoods, U.S. Census data, proportions of neighborhoods on public assistance, and crime data) that were linked across clusters of contiguous, relatively homogenous Chicago, IL census tracts with respect to racial/ethnic and socioeconomic composition. Our analysis-an ecological-level, repeated cross-sectional design utilizing random-intercept logit models-with a sensitivity analysis using spatial models to control for spatial autocorrelation-revealed consistent associations between neighborhood social processes and maltreatment. Neighborhoods higher in collective efficacy, intergenerational closure, and social networks, and lower in disorder had lower proportions of neglect, physical abuse, and sexual abuse substantiated cases, controlling for differences in structural factors. Higher collective efficacy and social network size also predicted a lower proportion of substance-exposed infants. This research indicates that strategies to mobilize neighborhood-level protective factors may decrease child maltreatment more effectively than individual and family-focused efforts alone.

Actual concept of "probiotics": is it more functional to science or business?

It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics. We believe this is due in part to the current regulatory framework, lack of a clear definition of a probiotic, the ease with which currently defined probiotics can be positioned in the market place, and the enormous profits earned for minimum investment in research. To avoid this, we believe the following two actions are mandatory: international guidelines by a forum of stakeholders made available to scientists and clinicians, patient organizations, and governments; public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.

The Effects of Two Novel Copper-Based Formulations on Helicobacter pylori.

We investigated the effects of two novel copper-based inorganic formulations for their activity against 60 isolates of Helicobacter pylori (Hp). The two copper-based formulations were tested against three NCTC Helicobacter pylori isolates and 57 clinical strains isolated from the UK and Italy in time-kill assays. Both copper-based formulations were bio-cidal against all Helicobacter pylori strains tested reducing the viable count by 4-5 log within 2 h. These two copper-based anti-microbial agents deserve further study in relation to the treatment of H. pylori-related gastric disease.

High prevalence of primary antibiotic resistance in Helicobacter pylori isolates in Italy.

BACKGROUND AND AIMS: H. pylori eradication with standard therapies is decreasing worldwide, mainly because of increased primary antibiotic resistance rates. We aimed to assess primary resistance in H. pylori isolates towards the most used antibiotics in clinical practice. METHODS: The study enrolled consecutive, dyspeptic, adult patients, never treated for H. pylori, who had underwent upper endoscopy. Gastric biopsies were taken for standard histology, and two further antral biopsies were used for H. pylori culture. Minimal inhibitory concentrations (MIC) >/= 1, >/= 8 and >/= 1 mg/L were used as break point for clarithromycin, metronidazole, and levofloxacin resistance, respectively. RESULTS: Bacterial culture was successful in 145 (94%) out of 154 infected patients. Resistance towards at least one antibiotic was detected in 111 (76.6%) isolated, and multiple antibiotic resistance in 35.2% of cases. Primary resistance towards clarithromycin, metronidazole, and levofloxacin was detected in 51 (35.2%), 86 (59.3%), and in 32 isolated (22.1%), respectively. Levofloxacin resistance was significantly associated with the male sex (OR: 11.3, 95% CI = 1.2-103; P = 0.03), whilst females were at a higher risk of being infected with bacterial strains harbouring a double clarithromycin and metronidazole resistance (OR: 4.9, 95% CI = 1.2-19.8, P = 0.02). CONCLUSION: Our data indicate a very high primary resistance rate towards the most used antibiotics in H. pylori isolates. The efficacy of standard eradication therapies is expected to further decrease in the next years.

Clinical presentation and risk factors of inflammatory bowel disease in Sri Lanka.

BACKGROUND AND AIMS: There have been very few studies on inflammatory bowel disease (IBD) in Sri Lanka. This study was undertaken to determine the clinical presentation and whether a western style diet or infection with geo-helminths were associated with the condition. METHODS: Three questionnaires were given to the patients: one relating to diet, one relating to clinical presentation and one relating to quality of life. The disease was confirmed endoscopically and histologically. Faeces were examined for parasites. RESULTS: Forty four patients were enrolled (43-ulcerative colitis; 1-Crohn's Disease). All but one had ulcerative colitis. Most had no family history of disease. The peak age of onset was 21-40 y and 63% gave a history of more than 6 months symptoms prior to diagnosis. Clinical presentation was similar to cases in western countries although milder with less severe life-events. None of them had undergone surgery. All patients ate a rice-based diet and none ate bread made of refined flour. Only 2 patient was infected with a geo-helminth. CONCLUSIONS: Eating bread made of refined flour is not related to development of IBD in these patients. The prevalence of geo-helminths in the study population corresponded to the general population average. Delay in diagnosis occurs because of an initial assumption that the cause of symptoms is infective. A National Register of non-infectious gastrointestinal disease would aid the epidemiology and allocation of funding to this inflammatory condition.

Structural bacterial molecules as potential candidates for an evolution of the classical concept of probiotics.

A large number of experimental and clinical studies published in recent years have demonstrated the beneficial role of probiotic bacteria in the health of the host. However, because the different receptors of the innate immune system can recognize only specific bacterial molecular patterns, knowledge of the role played by individual probiotic molecular patterns is essential to move from the current confused era of live probiotic bacteria to the era of the pharmacobiotic strategies. This article reviews the current knowledge on the probiotic activities of bacterial structural molecules (nucleic acids and surface molecules), which represent the fundamental basis to set up experimental and clinical studies in this emerging field with very promising and potentially invaluable future prospects.

Colonization by Helicobacter pylori of leprosy patients in Spain: immunomodulation to low molecular weight antigens of H. pylori.

We studied the prevalence of Helicobacter pylori in patients with leprosy and the effects of co-infection on the immune response to Helicobacter antigens in the polar groups of leprosy (lepromatous and tuberculoid). We showed that there is no difference in the prevalence of H. pylori in patients with leprosy as compared to a non-leprosy population. We also demonstrated that the immune response to low molecular weight H. pylori antigens (35, 26 and 19 kDa) differs in patients with lepromatous as compared to those with tuberculoid leprosy. In lepromatous leprosy, we show that there is a higher prevalence of the 35 and 26 kDa antigens, but a lower prevalence of the 19 kDa antigen. These immunological results are consistent with previous histopathological studies illustrating a more severe gastrointestinal inflammation in lepromatous patients; importantly, a response to the 35 kDa antigen is recognized as a marker for the development of ulcerative disease.