Santiago Vivas

Presence of Bacterial Infection in Bleeding Cirrhotic Patients Is Independently Associated with Early Mortality and Failure to Control Bleeding

Bacterial infection is strongly associated with gastrointestinal bleeding in cirrhotic patients and seems to be related with the failure to control bleeding. The aims of this study were to assess the influence of infections on the failure to control bleeding and death in cirrhotic patients without antibiotic prophylaxis. Ninety-one consecutive bleeding cirrhotic patients were analyzed. Bleeding was managed using somatostatin with sclerotherapy for active bleeding. Screening for bacterial infection (analysis and culture of blood, urine, ascitic and other fluids, together with chest radiography) was made at time 0 and when clinical signs suggested infection. The cause of bleeding was variceal in 72 (79%) patients. Failure to control bleeding occurred in 24 (26%) patients, and 10 (11%) of the patients died. Compared with the group without infection, failure to control bleeding (65% vs 15%; P < 0.001) and mortality (40% vs 3%; P < 0.001), were observed more frequently in patients with infection. Multivariate analysis showed that bacterial infection (OR = 9.7; P < 0.001) and the presence of shock (OR = 3.5; P < 0.05) were independently associated with failure to control bleeding. Bacterial infection (OR = 12.6; P < 0.01), encephalopathy (OR = 6.9; P < 0.05), and shock (OR = 5.8; P < 0.05) were identified as predictive of death. In conclusion, in bleeding cirrhotic patients bacterial infection is associated with failure to control bleeding as well as mortality.

Differences of small intestinal bacteria populations in adults and children with/without celiac disease: Effect of age, gluten diet, and disease

Background: Scientific evidence has revealed microecological changes in the intestinal tract of celiac infants. The objective of this work is the study of bacterial differences in the upper small intestine in both adults (healthy, untreated celiac disease [CD], and CD treated with a gluten‐free diet) and children (healthy and untreated CD). Methods: Intestinal bacterial communities were identified by 16S rRNA gene sequencing of DNA extracted from duodenal biopsies. Results: Analysis of the sequences from adults and children showed that this niche was colonized by bacteria affiliated mainly with three phyla: Firmicutes, Proteobacteria, and Bacteroidetes. In total, 89 different genera were identified in adults and 46 in children. Bacterial richness was significantly lower in the children than in the adults. A global principal component analysis of the bacterial communities of both healthy and untreated CD patient groups (including both children and adults) revealed a strong effect of age in principal component 1—clustering all adults and children separately—and a possible effect of the disease in adults with untreated patients clustering separately. Conclusions: There are bacterial differences in the upper small intestine between untreated children CD patients and untreated CD adults due to age. There are bacterial differences in the upper small bacteria microbiota between treated and untreated CD adults due to treatment with a gluten‐free diet. (Inflamm Bowel Dis 2011;)

Age-Related Clinical, Serological, and Histopathological Features of Celiac Disease

BACKGROUND:Celiac disease (CD) is a common disorder in children and adults. However, limited data are available when comparing differences between both populations.AIMS:To prospectively evaluate and compare the clinical and histological features present at diagnosis in a cohort of celiac children and adults.METHODS:Consecutive new cases diagnosed between 2000 and 2006 were prospectively included (66 children and 54 adults). The clinical spectrum was categorized in two groups: (a) typical (malabsorption, chronic diarrhea, or failure to thrive) and (b) oligosymptomatic (abdominal pain, anemia, hypertransaminasemia, or screening in risk groups or in relatives). The histological results were divided into mild (i.e., Marsh I, II, and IIIA) and severe (i.e., Marsh IIIB, IIIC). In all cases, the human antitissue transglutaminase IgA antibodies (TTGA) were determined.RESULTS:Overall, a female/male ratio (2.6:1) was observed. This ratio was significantly higher in adults (5.7:1) than in children (1.6:1) (P = 0.009). Typical symptoms were present in 62.5% children versus 31% adults (P = 0.01). The average time to diagnosis after the appearance of symptoms was 7.6 months for children and 90 months for adults (P < 0.001). TTGA levels were higher in children and correlated with age (P < 0.001) and with the degree of villous atrophy (P < 0.001). Histological analysis revealed a marked atrophy in 86% children versus 52% adults (P < 0.001). The degree of villous atrophy was inversely correlated with age (P < 0.001). Classic symptoms were also associated with more severe villous atrophy.CONCLUSIONS:At initial diagnosis, CD shows age-related differences, which consist of more evident clinical and histological features in children. Furthermore, IgA TTGA levels correlate both with the degree of villous atrophy and with the patients age.

Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces

Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available. Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces. Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody. Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients. Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867.

Palliative treatment of malignant obstruction of gastric outlet using an endoscopically placed enteral wallstent

Surgical gastrojejunostomy is the standard treatment for malignant gastric outlet obstruction, although it is associated with significant morbidity and mortality. The aim of this study was to evaluate the efficacy and feasibility of a newly designed expandable metal stent (Wallstent Enteral) to treat malignant gastric outlet obstruction. Six patients (five women, one man; mean age 76 years) underwent stenting. Stents 20–22 mm in diameter and 60–90 mm in length were deployed through a duodenoscope channel under endoscopic and fluoroscopic control, without previous stricture dilation. In all six cases the stent was adequately positioned and food intake was possible in the next 24 h. The mean time for hospital discharge was 2.5 days (1–5 days), without complications related to the procedure. Five patients died in the follow-up from progression of their cancer and one remains alive; none had recurrent obstruction. The median survival time was 9 weeks (95% CI: 3–15 weeks). In conclusion, endoscopic self-expandable stent (Wallstent Enteral) placement is safe and effective palliation for malignant gastric outlet obstruction and appears to be a therapeutic alternative to surgical gastrojejunostomy.

Diversity of the cultivable human gut microbiome involved in gluten metabolism: isolation of microorganisms with potential interest for coeliac disease

Gluten, a common component in the human diet, is capable of triggering coeliac disease pathogenesis in genetically predisposed individuals. Although the function of human digestive proteases in gluten proteins is quite well known, the role of intestinal microbiota in the metabolism of proteins is frequently underestimated. The aim of this study was the isolation and characterisation of the human gut bacteria involved in the metabolism of gluten proteins. Twenty-two human faecal samples were cultured with gluten as the principal nitrogen source, and 144 strains belonging to 35 bacterial species that may be involved in gluten metabolism in the human gut were isolated. Interestingly, 94 strains were able to metabolise gluten, 61 strains showed an extracellular proteolytic activity against gluten proteins, and several strains showed a peptidasic activity towards the 33-mer peptide, an immunogenic peptide in patients with coeliac disease. Most of the strains were classified within the phyla Firmicutes and Actinobacteria, mainly from the genera Lactobacillus, Streptococcus, Staphylococcus, Clostridium and Bifidobacterium. In conclusion, the human intestine exhibits a large variety of bacteria capable of utilising gluten proteins and peptides as nutrients. These bacteria could have an important role in gluten metabolism and could offer promising new treatment modalities for coeliac disease.

Human recombinant anti-transglutaminase antibody testing is useful in the diagnosis of silent coeliac disease in a selected group of at-risk patients.

Background Functional dyspepsia, unexplained chronic hypertransaminasaemia (CHT) and hepatitis C virus (HCV) are common gastrointestinal situations that have been related to coeliac disease. Antibodies to tissue transglutaminase (tTG) have been claimed recently to be highly effective as a screening method for coeliac disease. Aim To assess the prevalence of coeliac disease by means of detection of antibodies against human tTG in the abovementioned groups of patients. Patients and methods A control group consisted of 165 normal blood donors. Patient groups comprised 90 CHT patients, 102 HCV patients and 92 functional dyspepsia patients. All patients were tested for anti‐tTG (immunoglobulin A, IgA) antibodies. Anti‐endomysium (IgA) antibodies (AEA) and antigliadin (IgA) antibodies (AGA) and antigliadin (immunoglobulin G, IgG) antibodies (AGG) were also tested. When anti‐tTG or AEA was positive, a duodenal biopsy was recommended. Results One of 165 blood donors, three of 92 functional dyspepsia patients, four of 90 CHT patients and none of 102 HCV patients were positive for anti‐tTG antibodies. In the anti‐tTG‐positive group, all but one were AEA‐positive. There were no AEA‐ or AGA IgA‐positives that revealed a negative anti‐tTG test. Duodenal biopsy confirmed a diagnosis of coeliac disease in all the cases. Statistically significant differences were found between the controls and the functional dyspepsia group and between the controls and the CHT group, but not between the controls and the HCV group. Conclusions Both CHT and functional dyspepsia may represent a true oligosymptomatic form of coeliac disease. In such conditions, the detection of anti‐tTG antibodies is useful as a screening method. Coeliac disease is not an autoimmune manifestation of HCV, so screening for coeliac disease in HCV patients cannot be recommended.

The value of an immune response to Mycobacterium tuberculosis in patients with chronic posterior uveitides revisited: utility of the new IGRAs

PurposeTo explore the utility of a specific immune response to Mycobacterium tuberculosisin a population of immunosuppressed idiopathic chronic posterior uveitis patients, by means of a tuberculosis-specific interferon-γrelease assay.DesignProspective, interventional case series.MethodsA total of 31 referred patients with severe idiopathic chronic uveitis or panuveitis and 52 controls were screened for a specific immune response to tuberculosis. After ruling-out specific uveitis entities, presumed tuberculosis-related uveitis was initially considered when ophthalmologic findings were consistent with tubercular uveitis, and a specific immune response to M. tuberculosisconfirmed by QuantiFERON, despite inability to detect M. tuberculosis. Clinical responses to antitubercular treatment were recorded.Results:The prevalence of an immune response to M. tuberculosiswas 15.38% in controls and 32.25% in uveitis patients (OR=2.619, P=0.07). Two patients were QuantiFERON indeterminate (6.4%). After excluding seven specific uveitis entities (OR=3.66, P=0.03), eight QuantiFERON-positive and one QuanTIFERON-negative uveitis patients were initially treated for presumed tuberculosis-related uveitis. All but one had no evidence of active systemic involvement. None had been previously diagnosed with tuberculosis, but unsuccessfully treated with immunosuppressors. After a 9-month tuberculostatic treatment, seven QuantiFERON -positive and one QuantiFERON-negative patients exhibited decreased intraocular inflammation, visual acuity improvement, and no relapses. Estimated QuantiFERON sensitivity and specificity were 82 and 100%, respectively, with a PPV=100% and an NPV=86%.Conclusions:QuantiFERON was useful for antituberculous treatment decision-making in chronic posterior uveitis immunosuppressed patients from areas with an intermediate-high prevalence of tuberculosis.

Factors Determining Colorectal Cancer: The Role of the Intestinal Microbiota.

The gastrointestinal tract, in particular the colon, holds a complex community of microorganisms, which are essential for maintaining homeostasis. However, in recent years, many studies have implicated microbiota in the development of colorectal cancer (CRC), with this disease considered a major cause of death in the western world. The mechanisms underlying bacterial contribution in its development are complex and are not yet fully understood. However, there is increasing evidence showing a connection between intestinal microbiota and CRC. Intestinal microorganisms cause the onset and progression of CRC using different mechanisms, such as the induction of a chronic inflammation state, the biosynthesis of genotoxins that interfere with cell cycle regulation, the production of toxic metabolites, or heterocyclic amine activation of pro-diet carcinogenic compounds. Despite these advances, additional studies in humans and animal models will further decipher the relationship between microbiota and CRC, and aid in developing alternate therapies based on microbiota manipulation.

Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in celiac disease patients

Objectives:Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring.Methods:We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously.Results:Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP.Conclusions:Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.