Breath Tests for the Non-invasive Diagnosis of Small Intestinal Bacterial Overgrowth: A Systematic Review With Meta-analysis

Background/Aims@#Small intestinal bacterial overgrowth (SIBO) diagnosis is usually based on non-invasive breath tests (BTs), namely lactulose BT (LBT) and glucose BT (GBT). However, divergent opinions and problems of parameter standardization are still controversial aspects. We aim to perform a meta-analysis to analyze diagnostic performance of LBT/GBT for SIBO diagnosis. @*Methods@#We searched in main literature databases articles in which SIBO diagnosis was achieved by LBT/GBT in comparison to jejunal aspirate culture (reference gold standard). We calculated pooled sensitivity, specificity, positive, and negative likelihood ratios and diagnostic odd ratios. Summary receiver operating characteristic curves were drawn and pooled areas under the curve were calculated. @*Results@#We selected 14 studies. Pooled sensitivity of LBT and GBT was 42.0% and 54.5%, respectively. Pooled specificity of LBT and GBT was 70.6% and 83.2%, respectively. When delta over baseline cut-off > 20 H2 parts per million (ppm) was used, GBT sensitivity and specificity were 47.3% and 80.9%; when the cutoff was other than and lower than > 20 ppm, sensitivity and specificity were 61.7% and 86.0%. In patients with abdominal surgery history, pooled GBT sensitivity and specificity gave the impression of having a better performance (81.7% and 78.8%) compared to subjects without any SIBO predisposing condition (sensitivity = 40.6% and specificity = 84.0%). @*Conclusions@#GBT seems to work better than LBT. A cut-off of delta H2 expired other than and lower than > 20 ppm shows a slightly better result than > 20 ppm. BTs demonstrate the best effectiveness in patients with surgical reconstructions of gastrointestinal tract.

Biological markers for non-celiac gluten sensitivity: a question awaiting for a convincing answer

Non Celiac Gluten Sensitivity [NCGS] is characterized by immunological, morphological or symptomatic manifestations precipitated by gluten ingestion in individuals without celiac disease [CD]. The most important challenge in NCGS is the diagnosis, currently based only on clinical observation. The "Salerno criteria" have been pointed out to achieve a reliable diagnosis even if they lack immediacy and practicality, thus making questionable patient's adherence. Therefore, biological indicators supporting the clinical diagnosis of NCGS are advisable. For these reasons, many attempts have been performed in order to identify possible serological, immunological, histopathological, immunohistochemical and pathophysiological aspects characterizing this condition with the aim of using them for diagnostic purposes. In the present narrative review, we carried out an update of the current scenario of potential markers of NCGS. The main fault of available studies is that, in most cases investigations have been pointed out towards molecules, which cannot be searched in the current laboratories of clinical analysis. Therefore, the matter has been confined within basic research. Additionally, in these studies, sensitivity and specificity of biological markers were not computable. This is a relevant limit, since an ideal test for NCGS should have a good discriminative power against both CD and other causes of microscopic enteritis. Until now, serological tests have failed, while the search for a soluble marker indicative of activation of innate immune system as well as immunohistochemistry could be the promising bases for the development of appropriate investigations in the future

Pathological and clinical correlation between celiac disease and pathological and clinical correlation between celiac disease andpathological and clinical correlation between celiac disease and helicobacter pylori infection; a review of controversial rep

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease [CD] and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori [H. pylori] infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed [PubMed Central], Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection

Why do we still have Helicobacter Pylori in our Stomachs?

The existence of any infectious agent in a highly acidic human stomach is contentious, but the chance finding of Helicobacter pylori is by no means an accident. Once H. pylori colonises the gastric mucosa, it can persist for a lifetime, and it is intriguing why our immune system is able to tolerate its existence. Some conditions favour the persistence of H. pylori in the stomach, but other conditions oppose the colonisation of this bacterium. Populations with high and extremely low prevalence of H. pylori provide useful insights on the clinical outcomes that are associated with this type of infection. Adverse clinical outcomes including peptic ulcer disease and gastric cancer depend on a delicate balance between a harmless inflammation and a more severe kind of inflammation. Is the only good H. pylori really a dead H. pylori? The jury is still out.

Seronegative celiac disease: where is the specific setting?

The diagnosis of Celiac Disease [CD] relies on the concordance of pathological, serological, genetic and clinical features. For this reason, the diagnosis of CD is often a challenge. Seronegative celiac disease [SNCD] is defined by the negativity of anti-tissue transglutaminase antibodies in the presence of a positive histology on duodenal biopsy samples, i.e. inflammatory infiltrate of intra-epithelial lymphocytes [IELs > 25/100 enterocytes], mild villous atrophy and uneven brush border associated to human leukocyte antigen [HLA] haplotype DQ2 and/or DQ8. SNCD is characterized by mucosal deposits of tissue transglutaminase [tTG]/anti-tTG immuno-complexes. These may counteract the passage of anti-tTG into the bloodstream, thus explaining seronegativity. Another reason for seronegativity may be found in an incomplete maturation of plasma cells with a consequent failure of antibodies production. This condition often characterizes immunoglobulin deficiencies, and, indeed, SNCD is common in subjects with immunoglobulin deficiencies. The management of SNCD still remains debated. The treatment option for SNCD may be represented by gluten free diet [GFD], but the usefulness and appropriateness of prescribing GFD are controversial. Some evidences support its use only in SNCD subjects showing CD clear clinical picture and compatible HLA status. The choice of GFD administration could be linked to an investigation able to diagnose SNCD in no doubt even if a reliable test is not currently available. On these bases, a test helping the diagnosis of SNCD is justifiable and desirable

Furazolidone-based therapies for Helicobacter pylori infection: a pooled-data analysis

Furazolidone-based therapies are used in developing countries to cure Helicobacter pylori infection due to its low cost. The low bacterial resistance toward furazolidone may render appealing the use of this drug even in developed countries. However, some relevant safety concerns do exist in using furazolidone. This was a systematic review with pooled-data analysis of data regarding both eradication rate and safety of furazolidone-based therapies for H. pylori infection. Intention-to-treat [ITT] and per-protocol [PP] eradication rates were calculated. Following furazolidone-based first-line therapy, H. pylori eradication rates were 75.7% and 79.6% at ITT and PP analysis, respectively [P<0.001]. The overall incidence of side effects and severe side effects were 33.2% and 3.8%, respectively. At multivariate analysis, only high-dose furazolidone was associated with increased therapeutic success [OR: 1.5, 95% CI: 1.3-2.7; P<0.001], while occurrence of side effects was relevant following treatment for a long duration [OR: 2.9, 95% CI: 2.2-4.1; P<0.001], high-dose furazolidone [OR: 2.3, 95% CI: 1.7-3.2; P<0.001] and bismuth-containing regimens [OR: 2.1, 95% CI: 1.5-2.8; P<0.001]. Furazolidone-based regimens usually achieve low eradication rates. Only a high-dose regimen improves the cure rate, but simultaneously increases the incidence of severe side effects. Therefore, we suggest that patients have to be clearly informed about the possible genotoxic and carcinogenetic effects for which furazolidone use is not approved in developed countries