Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes.

Background: Torsades de pointes (TdP) is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton-pump inhibitors (PPIs)-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far. Objectives: Aim of the present study is to evaluate whether PPI-induced hypomagnesemia actually has a significant clinical impact on the risk of TdP in the general population. Methods: Forty-eight unselected patients who experienced TdP were consecutively enrolled (2008-2017). Shortly after the first TdP episode, in those patients who did not receive magnesium sulfate and/or potassium or calcium replacement therapy, serum electrolytes were measured and their relationship with PPI usage analyzed. Results: Many patients (28/48, 58%) were under current PPI treatment when TdP occurred. Among TdP patients in whom serum electrolyte determinations were obtained before replacement therapy (27/48), those taking PPIs had significantly lower serum magnesium levels than those who did not. Hypomagnesemia occurred in ~40% of patients receiving PPIs (6/14), in all cases after an extended treatment (>2 weeks). In patients taking PPIs the mean QT-prolonging risk factor number was significantly higher than in those who did not, a difference which was mainly driven by lower magnesium levels. Conclusions: In unselected TdP patients, PPI-induced hypomagnesemia was common and significantly contributed to their cumulative arrhythmic risk. By providing clinical support to current recommendations, our data confirm that more awareness is needed when a PPI is prescribed, specifically as regards the risk of life-threatening arrhythmias.

Pattern of food intolerance in patients with gastro-esophageal reflux symptoms.

BACKGROUND: Many food items have been involved in gastro-esophageal reflux disease pathogenesis and dietary modification has been proposed as first-line treatment. Test-based exclusion diets have shown to significantly reduce reflux symptoms. We aimed to assess the patterns of food intolerance in a series of patients with typical gastro-esophageal reflux symptoms (GERS). METHODS: We retrospectively evaluated all patients with typical reflux symptoms, attending the Centre Study Association on Food Intolerance and Nutrition of Ferrara from January 2010 to October 2015, who resulted positive to at least one food item at the Leucocytotoxic Test. The presence and severity of typical GERS (heartburn and/or acid regurgitation) were assessed using the Gastro-esophageal Reflux Disease Impact Scale (GIS) questionnaire. Only individuals with a GIS Score of at least 5 points were included. RESULTS: Almost all patients (91.1%) were intolerant to at least 5 food items. The most frequent food intolerance (more than 33% of patients) were found for milk (55.4%), lettuce (46.4%), coffee (43.7%), brewer's yeast (42.9%), pork (42.9%), tuna (37.5%), rice (35.7%), sole (34.8%), asparagus (34.8%) and eggs (33.9%). Nine different clusters of food intolerance were detected. CONCLUSIONS: Patients with typical gastro-esophageal reflux symptoms seem to have intolerance to multiple food items, some of which (lettuce, brewer's yeast, tuna, rice, sole and asparagus) have not yet been associated to gastro-esophageal reflux disease.

PCR detection of segmented filamentous bacteria in the terminal ileum of patients with ulcerative colitis.

OBJECTIVES: Segmented filamentous bacteria (SFB) have been detected in a wide range of different animal. Recently, the presence of SFB-like bacteria was shown in biopsies of the terminal ileum and ileocecal valve of both patients with ulcerative colitis and control subjects. The aim of this study was to verify whether PCR methods could be used for the detection of SFB in biopsy of patients with ulcerative colitis and its relationships with the disease stage. METHODS: PCR methods were used to identify SFB in biopsies from the terminal ileum of patients with ulcerative colitis, showing that this approach represents a useful tool for the detection of SFB presence and analysis of the bacterial load. RESULTS: Our analysis detected SFB in all faecal samples of children at the time of weaning, and also show that putative SFB sequences are present in both patients with ulcerative colitis and control subjects. Results obtained using real-time quantitative PCR analysis confirm the presence of putative SFB sequences in samples from the terminal ileum of patients with ulcerative colitis and in control subjects. CONCLUSIONS: The presence of putative SFB sequence in both patients with ulcerative colitis and control subject suggests that SFB cannot be considered as being uniquely associated with the disease. The second conclusion is that among the patients with ulcerative colitis, a tendency does exist for active disease samples to show higher SFB load, opening new perspectives about possible identification and pharmacological manipulation of SFB-mediated processes for new therapeutic strategy.

Guidelines for the management of Helicobacter pylori infection in Italy: The III Working Group Consensus Report 2015.

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Test-based exclusion diets in gastro-esophageal reflux disease patients: a randomized controlled pilot trial.

AIM: To investigate the clinical response of gastro-esophageal reflux disease (GERD) symptoms to exclusion diets based on food intolerance tests. METHODS: A double blind, randomized, controlled pilot trial was performed in 38 GERD patients partially or completely non-responders to proton pump inhibitors (PPI) treatment. Fasting blood samples from each patients were obtained; leukocytotoxic test was performed by incubating the blood with a panel of 60 food items to be tested. The reaction of leukocytes (rounding, vacuolization, lack of movement, flattening, fragmentation or disintegration of cell wall) was then evaluated by optical microscopy and rated as follows: level 0 = negative, level 1 = slightly positive, level 2 = moderately positive, and level 3 = highly positive. A "true" diet excluding food items inducing moderate-severe reactions, and a "control" diet including them was developed for each patient. Then, twenty patients received the "true" diet and 18 the "control" diet; after one month (T1) symptoms severity was scored by the GERD impact scale (GIS). Hence, patients in the "control" group were switched to the "true" diet, and symptom severity was re-assessed after three months (T2). RESULTS: At baseline (T0) the mean GIS global score was 6.68 (range: 5-12) with no difference between "true" and control group (6.6 ± 1.19 vs 6.7 ± 1.7). All patients reacted moderately/severely to at least 1 food (range: 5-19), with a significantly greater number of food substances inducing reaction in controls compared with the "true" diet group (11.6 vs 7.0, P < 0.001). Food items more frequently involved were milk, lettuce, brewer's yeast, pork, coffee, rice, sole asparagus, and tuna, followed by eggs, tomato, grain, shrimps, and chemical yeast. At T1 both groups displayed a reduction of GIS score ("true" group 3.3 ± 1.7, -50%, P = 0.001; control group 4.9 ± 2.8, -26.9%, P = 0.02), although the GIS score was significantly lower in "true" vs "control" group (P = 0.04). At T2, after the diet switch, the "control" group showed a further reduction in GIS score (2.7 ± 1.9, -44.9%, P = 0.01), while the "true" group did not (2.6 ± 1.8, -21.3%, P = 0.19), so that the GIS scores didn't differ between the two groups. CONCLUSION: Our results suggest that food intolerance may play a role in GERD symptoms development, and leucocytotoxic test-based exclusion diets may be a possible therapeutic approach when PPI are not effective or indicated.

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.

Genome sequences of segmented filamentous bacteria in animals: implications for human research.

Experimental studies indicate that segmented filamentous bacteria (SFB) can recapitulate fundamental immune responses, particularly in reference to Th 17 and regulatory T-cell activity. The recent description of whole genomic DNA sequences of mouse and rat SFBs and the comparison between these sequences opens new important perspectives. In particular this knowledge allows to perform quali-quantitative studies in human beings regarding these yet unculturable anaerobic bacteria. The comparative analysis of rat and mouse SFB 16S rRNA sequences suggests the existence of highly conserved regions that could represent SFB-specific molecular targets potentially useful to develop PCR probes for study SFB in humans. These molecular tools may be of inestimable value to evaluate the possible role played by SFB in the immune system physiology, as well as its potential involvement in human chronic inflammatory and autoimmune diseases.

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.

Morphology of segmented filamentous bacteria and their patterns of contact with the follicle-associated epithelium of the mouse terminal ileum: implications for the relationship with the immune system.

Recent evidence indicates that segmented filamentous bacteria (SFB), "Candidatus Arthromitus", play a unique role in different aspects of the maturation of the immune system, including T cell responses. Thus, it seems particularly relevant in this moment to shortly review the information on these bacteria and their relationship with the immune system, and to actively investigate their morphological aspects. We distinguished a developmental form from a vegetative form of these organisms. These different forms have distinct roles in the life cycle: the developmental form permits a rapid growth of the organisms while the vegetative form permits the attachment of SFB to the follicular epithelium. We have also given special attention to the modes of contact between SFB and the epithelial cells of the terminal ileum to better understand the unique relationship between these bacteria and the immune system.

Reflux symptoms in professional opera choristers.

BACKGROUND AND AIMS: A specific, occupation-related susceptibility of professional singers to experience gastroesophageal reflux was hypothesized. We investigated the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers in comparison with a general population sample. METHODS: A total of 351 professional opera choristers from well-known chorus in different Italian regions were identified and a sample of 578 subjects residing in the same areas with a similar distribution in age and sex was selected. Reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits were investigated in both study groups through a structured questionnaire. Prevalence rate ratios, adjusted for sex, age, body mass index, smoking status, alcohol consumption, and other confounding factors, were computed. RESULTS: Opera choristers reported a statistically significant higher prevalence of heartburn, regurgitation, cough, and hoarse voice than the population sample, with adjusted prevalent rate ratios of 1.60 (95% confidence interval [CI], 1.32-1.94), 1.81 (95% CI, 1.42-2.30), 1.40 (95% CI, 1.18-1.67), and 2.45 (95% CI, 1.97-3.04), respectively. Regurgitation appeared to be associated consistently with the cumulative lifetime duration of singing activity (P = .04) and with the weekly duration of singing activity (P = .005) when different multivariate models were applied. CONCLUSIONS: Opera choristers reported a higher prevalence of reflux symptoms than the population sample. Future studies will be needed to clarify whether gastroesophageal reflux in professional opera choristers is stress-induced and therefore may be considered as a work-related disease.