Helicobacter pylori and Respiratory Diseases: 2021 Update.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium involved in the development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue. Unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency have also been related to H. pylori infection, whereas for other extra-gastric diseases, the debate is still open. In this review, we evaluate and discuss the potential involvement of H. pylori infection in the pathogenesis of several respiratory diseases. A MEDLINE search of all studies published in English from 1965 to 2021 was carried out. Controversial findings have been reported in patients with bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, lung cancer, tuberculosis, cystic fibrosis, and sarcoidosis. Most of the available literature is concerned with case-control studies based on seroprevalence, with a small sample size and low consideration of confounders, which represents a potential issue. So far, there is no clear evidence of a causal association between H. pylori infection and respiratory diseases, and larger studies with appropriate epidemiological design are required.

Role of Compositum Zeolite® in management of inflammatory bowel disease: a pilot study.

BACKGROUND: Zeolites are crystalline mineral aluminosilicate compounds with microporous structures of tetrahedrons and huge porosity. In the gut, these silicates act as adsorbents, ion-exchangers, catalysts, detergents or antidiarrheic agents. In addition to its well-known antioxidant effect, a new potential advantage of Zeolite could be the microbiome modulation. In this scenery, we aimed to investigate the effect of this compound on inflammation among inflammatory bowel disease patients, assessing both clinical activity and inflammatory markers. METHODS: This was an open one branch pilot study involving 20 IBD patients, both affected with Crohn's disease and ulcerative colitis affering to San Giovanni Antica Sede Hospital, Città della Salute e della Scienza in Turin. Each patient was given Compositum Zeolite® 6 g/die for 56 days; follow-up time was 60 days from the end of Zeolite therapy. Primary outcomes of the study were to evaluate the improvement of the quality of life (Partial Mayo score or Harvey Bradshaw Index) and the compliance to therapy, while secondary outcome was the reduction of calprotectin value. RESULTS: Of the twenty patients enrolled, 4 did not attend the scheduled check-up visit and 2 reported non-adherence to the therapy with Compositum Zeolite® so these 6 patients were considered as drop out and their data were not included in statistical analysis. So, compliance rate was 70%, that is similar to general adherence to therapy in our setting. Regarding Ulcerative Colitis patients, at the moment of enrolment mean Mayo Partial Score (MPS) was 3.09 (CI: 1.76-4.41) while after 8 weeks of Compositum Zeolite® supplementation the mean MPS was 2.72 (CI: 1.45-4.00) (P=0.57) and after 60 days of follow-up mean MPS was 1.9 (CI: 0.85-2.97) (P=0.24). As Crohn's disease patients are concerned, HBI Score at enrolment was 5.3 (CI: 3.38-7.29) while mean score after 8 week of therapy was 4 (CI: 2.85-5.15) (P=0.042) and after 60 days of follow-up mean score was 3.1 (CI: 1.48-4.87) (P=0.18). Mean calprotectin value at enrolment was 925.64 (CI: 451.83-1399.45). while after 2 months of Compositum Zeolite® addon therapy was 952.72 (CI: 492.73-1412.73); P value 0.93. After 2 months of follow-up mean value was 724.45 (CI: 240.15-1208.73) P value 0.3. CONCLUSIONS: Compositum Zeolite® has a compliance rate similar to the other prescribed therapies and is a good addon therapy to improve activity indexes, mainly in Crohn's disease. It also seems to improve inflammatory indexes, even if maybe dose or time of therapy were insufficient to reach a full negativization of these parameters.

Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients.

Background and Objectives: In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. Materials and Methods: A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. Results: In the entire cohort, only 8 cases of heterozygous mutations of TPMT were observed, corresponding to 4% mutated haplotype rate, much lower than that reported in literature (close to 10%). No homozygous mutation was found. Regarding the TPMT allelic variants, we did not find any statistically significant difference between patients who tolerated azathioprine and those who suffered from adverse events. (OR = 0.77, 95% CI = 0.08-7.72; p = 0.82). Conclusions: According to our study, in IBD patients, the search for TPMT gene mutations before starting treatment with azathioprine is not helpful in predicting the occurrence of adverse events. Importantly, patients with allelic variants should not be denied the therapeutic option of azathioprine, as they may tolerate this drug.

Irritable bowel syndrome: the clinical approach.

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder which presents with abdominal pain associated with alteration of bowel habits. IBS is a common condition affecting 9-23% of the general population, being the 80% female, with considerable impact on quality of life and health care costs. The exact pathogenesis of IBS remains elusive, but is clearly multifactorial and includes environmental and host factors. Management of patients with IBS is challenging since diagnosis and treatment could require several approaches with unsatisfactory results. In any case, the diagnosis of IBS is based on the positive identification of symptoms consistent with this condition and by excluding an underling organic disease. Before choosing therapeutic options, a strong reassuring physician-patient relationship is crucial. The therapeutic approach of IBS may consist of both non-pharmacological therapies and pharmacotherapy and should be based on prevalent symptomatology. Lifestyle modifications such as stress reduction and increased physical activity seem to be useful to improve symptoms and should be encouraged. The same for dietary modifications that represent an important first-line therapeutic option. The pharmacological treatment should take into account the predominant symptom and test one drug at a time with a predefined time point for effectiveness evaluation and dosage adjustment. This clinical review offers an updated overview on epidemiology, pathogenesis, diagnosis and treatment of IBS.

A Case of Intestinal Mastocytosis Misdiagnosed as Crohn's Disease.

Systemic mastocytosis (SM) is a rare, heterogeneous and progressive disease, characterized by the accumulation of atypical mast cells in various organs, including the gastrointestinal tract. Gastrointestinal symptoms are present in up to 80% of patients with SM, the most common being abdominal pain, diarrhea, nausea and vomiting. Up to 50% of patients with SM do not have classical skin lesions at presentation, and in these patients the diagnosis of SM can be difficult for years. Here we report a case of SM that initially mimicked inflammatory bowel disease, although the patient showed poor response to steroid therapy. The right diagnosis was made only on the surgical specimen obtained after emergency surgery for intestinal obstruction. SM should therefore be considered in the diagnostic approach in patients with gastrointestinal symptoms not attributable to other pathologies and in cases of suspected inflammatory bowel disease with unusual course.

Power Doppler sonography to predict the risk of surgical recurrence of Crohn's disease.

PURPOSE: The aim of this work is to investigate the role of power Doppler sonography as an additional predictor of surgical recurrence in Crohn's disease. METHODS: A sample of 33 patients, with ileal or ileocolonic Crohn's disease, that had underwent intestinal resection, were retrospectively enrolled. All patients had bowel ultrasonography 7-16 months after resection. Power Doppler sonography of the preanastomotic ileum was evaluated as a possible prognostication tool to assess the risk of long-term need for reoperation. RESULTS: The absolute incidence of surgical recurrence in those who had a positive power Doppler was 42 %, while that of those who had a negative power Doppler was 28.6 %. Combining the power Doppler with bowel wall thickness, the surgical recurrence risk grew from 41.2 % of those with a positive power Doppler and thickness >3 mm to 55.6 % of those with a positive power Doppler and thickness >6 mm. CONCLUSIONS: Power Doppler look to be another useful prediction tool for the personalization of patient's care. It could be useful to perform power Doppler in all patients with a wall thickness >5 mm: for those who have a positive power Doppler it may be indicated as a more aggressive prophylactic therapy.

Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet.

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <-1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

Fecal calprotectin is an effective diagnostic tool that differentiates inflammatory from functional intestinal disorders.

BACKGROUND: The clinical pictures of functional gastrointestinal disorders and inflammatory diseases can be quite similar leading to inappropriate and expensive investigations. Objective. To investigate fecal calprotectin (FC) diagnostic performance in different gastrointestinal conditions. MATERIAL AND METHODS: Stool specimens of 66 outpatients referred for colonoscopy were collected for further FC determination. Diagnostic accuracy was assessed by the area under the curve (AUC). Sensitivity (Se), specificity (Sp), positive (PPV), and negative predictive values (NPV) were calculated according to the presence of inflammation and the main final diagnosis. RESULTS: Histological inflammation was found in 45 (68%) patients: 24 had a diagnosis of inflammatory bowel disease (IBD) while 21 reported miscellaneous conditions (5 microscopic colitis, 2 eosinophilic colitis, and 14 nonspecific chronic colitis). The diagnosis in the 21 (32%) patients without inflammation was irritable bowel syndrome (IBS). Median FC values were 268 µg/g (95% CI, 151-343) and 49 µg/g (95% CI, 23-101) in patients with and without inflammation, respectively (p = 0.0001). AUC value of FC was 0.811 (Se = 68.9%, Sp = 71.4%, PPV = 83.8%, and NPV = 56.3% with a cutoff value of 100 µg/g) for discriminating between patients with and without inflammation and 0.931 (Se = 87.5%, Sp = 90.5%, PPV = 91.3%, and NPV = 86.4% with a cutoff value of 150 µg/g) for discriminating between patients with IBS and IBD. Using the cutoff value recommended by the manufacturer (50 µg/g), we found Se =100%, Sp =52.4%, PPV =70.6%, and NPV =100% for the diagnosis of IBD. CONCLUSIONS: FC appears to be a reliable noninvasive biomarker of intestinal inflammation useful to improve the appropriateness of colonoscopy requests.

UPLC-MS/MS method for quantification of the azathioprine metabolites 6-mercaptoguanosine and 6-methylmercaptopurine riboside in peripheral blood mononuclear cells.

In the treatment of inflammatory bowel diseases, the use of azathioprine is increasing over the time. It has been demonstrated that the effectiveness of this therapy is modulated by the metabolism of azathioprine, which is mainly exerted by both thiopurine methyl-transferase and inosine triphosphatase enzymes. Several studies reported chromatographic methods to determine the amount of its metabolites in erythrocytes, but there are not reported methods to dose them in peripheral blood mononuclear cells (PBMCs). The development of a method capable to quantify azathioprine nucleoside metabolites in this compartment could give better information on drug penetration and metabolism in the active site. In this work, we validated a new chromatographic method suitable for the monitoring of the two major biologically active ribonucleos(t)ide metabolites of azathioprine in PBMCs: 6-thioguanosine and 6-methyl-mercaptopurine riboside. After PBMCs extraction from blood through separation on density gradient, samples underwent a de-phosphorylation procedure with acid phosphatase (only one aliquot for each sample) and were then treated with a protein precipitation protocol in acetonitrile, followed by UPLC-tandem-mass spectrometry analysis. The calibration curve for each metabolite in PBMC fitted a least squares model (weighed 1/X) from 0.048 to 25ng (r(2)=0.998). Both accuracy and precision parameters fitted FDA guidelines. We tested this method by monitoring the concentrations of each metabolite in PBMC from eight inflammatory bowel diseases affected patients, receiving azathioprine maintenance therapy with optimal results.