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.

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.

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.

A human domain antibody and Lewis b glycoconjugate that inhibit binding of Helicobacter pylori to Lewis b receptor and adhesion to human gastric epithelium.

Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

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.

Intestinal tuberculosis.

PURPOSE OF REVIEW: Intestinal tuberculosis (TB) is increasing due partly to the HIV pandemic. Its clinical presentation mimics inflammatory conditions such as Crohn's disease and malignancies, which are becoming more prevalent, so the diagnosis is problematic. RECENT FINDINGS: Greater awareness of intestinal TB is needed, both in countries where TB is endemic and developed countries with immigrant populations. Some strains of Mycobacterium tuberculosis are associated with more extrapulmonary disease and greater dissemination, thereby exacerbating the rise in HIV-associated extrathoracic TB. Recent retrospective and prospective studies are leading to the development of diagnostic algorithms. A wide range of imaging techniques is available for sampling and diagnosis. New biochemical, immunological and molecular diagnostic methods are being developed but must be standardized and validated. Developments in drug delivery will facilitate oral therapy even in patients suffering from malabsorption. SUMMARY: There is an increasing consensus on the risk factors and clinical presentations of intestinal TB. Imaging techniques, coupled with fine needle biopsies, are useful aids to diagnosis, but most important is a greater awareness of the condition by clinicians.

Presence of Helicobacter pylori in betel chewers and non betel chewers with and without oral cancers.

BACKGROUND: Betel chewing has been shown to predispose to periodontal disease and oral cancer. Studies show that people with gum disease are more likely to test positive for Helicobacter pylori (H. pylori). It is not known if the lesions produced by betel quid and the resulting, chemical changes predispose to colonization by H. pylori. Further the role of this organism in oral cancer is not known. Our objective was to determine the presence of H. pylori in oral lesions of thirty oral cancer patients and to determine the presence of IgG antibodies to H. pylori in oral cancer patients who are betel chewers and non betel chewers, healthy betel chewers and healthy non-betel chewers and to compare the presence of H. pylori in these four groups. This case control study was conducted at the Cancer Institute Maharagama and the Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura. METHODS: One hundred and seventy three subjects, of whom fifty three were patients presenting with oral cancer to the Cancer Institute Maharagama, sixty healthy betel chewers and sixty healthy non-betel chewers from the Religious and Welfare Service Centre Maharagama were tested for H. pylori by serology. Thirty oral biopsies from oral cancer patients were cultured under microaerophilic condition to isolate H. pylori. The statistic used was Chi-square test. RESULTS: Of the fifty-three oral cancer patients, forty-four were betel chewers. Among the 53 oral cancer patients examined, ten of forty-four (10/44 = 22.7%) patients who are betel chewers and four of nine (4/9 = 44.4%) patients who are non-betel chewers were detected positive for IgG antibody against H. pylori. In the healthy group (betel chewers and non betel chewers) ten (16.7%) of the healthy betel chewers tested positive for H. pylori by serology. None of the healthy non-betel chewers tested positive for H. pyloriFourteen [26.4%] of oral cancer patients tested positive for H. pylori by serology, of which two were also culture positive (Only thirty samples were cultured). The presence of H. pylori in betel chewers (with or without cancer) compared to non-betel chewers was statistically significant. (Chi-square test p < 0.05) The use of tobacco and areca nut in betel chewers was significant with the presence of H. pylori (p < 0.05). CONCLUSION: There is a significant higher proportion of H. pylori in betel chewers compared to non-betel chewers but not between oral cancer patients compared to patients without oral cancer. Hence Betel chewing may predispose to colonisation with H. pylori in the digestive tract through swallowing the quid or during betel chewing.

Diagnosis of Helicobacter pylori: invasive and non-invasive tests.

Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (e.g. histological examination, culture and rapid urease test) and by non-invasive techniques, such as serology, the urea breath test, urine/blood or detection of H. pylori antigen in stool specimen. Some non-invasive tests, such as the urea breath test and the stool antigen test, detect active infection: these are called 'active tests'. Non-invasive tests (e.g. serology, urine, near-patient tests) are markers of exposure to H. pylori but do not indicate if active infection is ongoing; these are 'passive tests'. Non-invasive test-and-treat strategies are widely recommended in the primary care setting. The choice of appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness.

Healthy Families America: ruminations on implementing a home visitation program to prevent child maltreatment.

Following a 1990 federal report forecasting a national child abuse and neglect epidemic, Prevent Child Abuse America (PCA America) promoted a home visitation program known as Healthy Families America (HFA). HFA achieved rapid adoption and implementation across the nation going from 25 sites in 1992 to 430 in a decade. In this article, the authors describe PCA America's approach to develop, promote, oversee, and evaluate a national home visitation program. Despite its promising growth, HFA has been criticized for failing to achieve the goal of preventing child maltreatment. HFA's past and present are critiqued based on theory and implementation practice of home visitation and its future projected from the perspective of insiders. Developing a better understanding of HFA's history will advance existing models of home visitation and add to the emerging knowledge base of child maltreatment prevention.

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.

Helicobacter pylori virulence factors in duodenal ulceration: A primary cause or a secondary infection causing chronicity.

Reports from countries with a high prevalence of Helicobacter pylori (H pylori) infection do not show a proportionately high prevalence of duodenal ulceration, suggesting the possibility that H pylori cannot be a primary cause of duodenal ulceration. It has been mooted that this discrepancy might be explained by variations in the prevalence of virulence factors in different populations. The aim of this paper is to determine whether the published literature gives support to this possibility. The relevant literature was reviewed and analyzed separately for countries with a high and low prevalence of H pylori infection and virulence factors. Although virulent strains of H pylori were significantly more often present in patients with duodenal ulcer than without the disease in countries with a low prevalence of H pylori infection in the population, there was no difference in the prevalence of virulence factors between duodenal ulcer, non - ulcer dyspepsia or normal subjects in many countries, where the prevalence of both H pylori infection and of virulence factors was high. In these countries, the presence of virulence factors was not predictive the clinical outcome. To explain the association between virulence factors and duodenal ulcer in countries where H pylori prevalence is low, only two papers were found that give little support to the usual model proposed, namely that organisms with the virulence factors are more likely than those without them to initiate a duodenal ulcer. We offer an alternative hypothesis that suggests virulence factors are more likely to interfere with the healing of a previously produced ulcer. The presence of virulence factors only correlates with the prevalence of duodenal ulcer in countries where the prevalence of H pylori is low. There is very little evidence that virulence factors initiate duodenal ulceration, but they may be related to failure of the ulcer to heal.

Precise role of H pylori in duodenal ulceration.

The facts that H pylori infection is commoner in duodenal ulcer (DU) patients than in the normal population, and that eradication results in most cases being cured, have led to the belief that it causes DU. However, early cases of DU are less likely than established ones to be infected. H pylori-negative cases are usually ascribed to specific associated factors such as non-steroidal anti-inflammatory drugs (NSAIDs), Crohn's disease, and hypergastrinaemia, but even after excluding these, several H pylori-negative cases remain and are particularly common in areas of low prevalence of H pylori infection. Moreover, this incidence of H pylori negative DU is not associated with a fall in overall DU prevalence when compared with countries with a higher H pylori prevalence. In countries with a high H pylori prevalence there are regional differences in DU prevalence, but no evidence of an overall higher prevalence of DU than in countries with a low H pylori prevalence. There is no evidence that virulence factors are predictive of clinical outcome. After healing following eradication of H pylori infection DU can still recur. Medical or surgical measures to reduce acid output can lead to long-term healing despite persistence of H pylori infection. Up to half of cases of acute DU perforation are H pylori negative. These findings lead to the conclusion that H pylori infection does not itself cause DU, but leads to resistance to healing, i.e., chronicity. This conclusion is shown not to be incompatible with the universally high prevalence of DU compared with controls.

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.

Comparison of image analysis software packages in the assessment of adhesion of microorganisms to mucosal epithelium using confocal laser scanning microscopy.

We have compared current image analysis software packages in order to find the most useful one for assessing microbial adhesion and inhibition of adhesion to tissue sections. We have used organisms of different sizes, the bacterium Helicobacter pylori and the yeast Candida albicans. Adhesion of FITC-labelled H. pylori and C. albicans was assessed by confocal microscopy. Four different Image analysis software packages, NIH-Image, IP Lab, Image Pro+, and Metamorph, were compared for their ability to quantify adhesion of the two organisms and several quantification methods were devised for each package. For both organisms, the dynamic range that could be detected by the software packages was 1x10(6)-1x10(9) cells/ml. Of the four software packages tested, our results showed that Metamorph software, using our 'Region of Interest' method, with the software's 'Standard Area Method' of counting, was the most suitable for quantifying adhesion of both organisms because of its unique ability to separate clumps of microbial cells. Moreover, fewer steps were required. By pre-incubating H. pylori with the glycoconjugate Lewis b-HSA, an inhibition of binding of 48.8% was achieved using 250 mug/ml Lewis b-HSA. The method we have devised using Metamorph software, provides a simple, quick and accurate way of quantifying adhesion and inhibition of adhesion of microbial cells to the epithelial surface of tissue sections. The method can be applied to organisms ranging in size from small bacteria to larger yeast cells.