Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

OBJECTIVES: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. METHODS: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. RESULTS: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. CONCLUSIONS: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI.

The role of diet on gut microbiota composition.

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

Gut barrier in health and disease: focus on childhood.

The gut barrier is a functional unit, organized as a multi-layer system, made up of two main components: a physical barrier surface, which prevents bacterial adhesion and regulates paracellular diffusion to the host tissues, and a deep functional barrier, that is able to discriminate between pathogens and commensal microorganisms, organizing the immune tolerance and the immune response to pathogens. Other mechanisms, such as gastric juice and pancreatic enzymes (which both have antibacterial properties) participate in the luminal integrity of the gut barrier. From the outer layer to the inner layer, the physical barrier is composed of gut microbiota (that competes with pathogens to gain space and energy resources, processes the molecules necessary to mucosal integrity and modulates the immunological activity of deep barrier), mucus (which separates the intraluminal content from more internal layers and contains antimicrobial products and secretory IgA), epithelial cells (which form a physical and immunological barrier) and the innate and adaptive immune cells forming the gut-associated lymphoid tissue (which is responsible for antigen sampling and immune responses). Disruption of the gut barrier has been associated with many gastrointestinal diseases, but also with extra-intestinal pathological condition, such as type 1 diabetes mellitus, allergic diseases or autism spectrum disorders. The maintenance of a healthy intestinal barrier is therefore of paramount importance in children, for both health and economic reasons. Many drugs or compounds used in the treatment of gastrointestinal disorders act through the restoration of a normal intestinal permeability. Several studies have highlighted the role of probiotics in the modulation and reduction of intestinal permeability, considering the strong influence of gut microbiota in the modulation of the function and structure of gut barrier, but also on the immune response of the host. To date, available weapons for the maintenance and repair of gut barrier are however few, even if promising. Considerable efforts, including both a better understanding of the gut barrier features and mechanisms in health and disease, and the development of new pharmacological approaches for the modulation of gut barrier components, are needed for the prevention and treatment of gastrointestinal and extraintestinal diseases associated with gut barrier impairment.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection.

BACKGROUND: Faecal microbiota transplantation (FMT) from healthy donors is considered an effective treatment against recurrent Clostridium difficile infection. AIM: To study the effect of FMT via colonoscopy in patients with recurrent C. difficile infection compared to the standard vancomycin regimen. METHODS: In an open-label, randomised clinical trial, we assigned subjects with recurrent C. difficile infection to receive: FMT, short regimen of vancomycin (125 mg four times a day for 3 days), followed by one or more infusions of faeces via colonoscopy; or vancomycin, vancomycin 125 mg four times daily for 10 days, followed by 125-500 mg/day every 2-3 days for at least 3 weeks. The latter treatment did not include performing colonoscopy. The primary end point was the resolution of diarrhoea related to C. difficile infection 10 weeks after the end of treatments. RESULTS: The study was stopped after a 1-year interim analysis. Eighteen of the 20 patients (90%) treated by FMT exhibited resolution of C. difficile-associated diarrhoea. In FMT, five of the seven patients with pseudomembranous colitis reported a resolution of diarrhoea. Resolution of C. difficile infection occurred in 5 of the 19 (26%) patients in vancomycin (P < 0.0001). No significant adverse events were observed in either of the study groups. CONCLUSIONS: Faecal microbiota transplantation using colonoscopy to infuse faeces was significantly more effective than vancomycin regimen for the treatment of recurrent C. difficile infection. The delivery of donor faeces via colonoscopy has the potential to optimise the treatment strategy in patients with pseudomembranous colitis.

Omega-3 fatty acids: a novel resort against gastrointestinal injury.

The integrity of gastric barrier derives from the balance between defending and damaging factors. In particular, prostaglandins play a relevant role in the maintenance of gastric homeostasis and prevention of peptic disease, at different levels. Omega-3 fatty acids, particularly eicosapentanoic acid, are the precursors of the third series of prostaglandins (with anti-inflammatory properties), also reducing the formation of the second series of prostaglandins (pro-inflammatory ones). Such a pathophysiological rationale brought to the experimental application, both in animal models and, more recently, in humans, of omega-3 fatty acids against gastrointestinal damage. Omega-3 fatty acids have shown interesting results in preventing different types of gastric damage in mouse models. A large retrospective case-control study on patients taking both anti-thrombotic therapy and eicosapentanoic acid showed (although only at unadjusted analysis) an inverse correlation between consumption of eicosapentanoic acid and gastrointestinal injury. Prospective, well-designed, comparative studies are warranted to clarify if omega-3 fatty acids may represent, or not, a novel resort against gastrointestinal injury.

Systematic review: Sprue-like enteropathy associated with olmesartan.

BACKGROUND: The onset of a sprue-like enteropathy in association with olmesartan therapy has been recently reported. AIMS: To perform a systematic review of the literature and describe three additional cases of olmesartan-associated enteropathy. METHODS: Electronic and manual bibliographic searches were performed to identify original reports in which subjects who were undertaking olmesartan developed a sprue-like enteropathy. Because of the scarcity of studies with adequate sample size, case series with less than 10 patients and case reports were also considered. Data extraction was performed independently by two reviewers. RESULTS: A total of 11 publications met our pre-defined inclusion criteria, for an overall number of 54 patients (including our series). Almost all patients presented with diarrhoea and weight loss. Normocytic normochromic anaemia and hypoalbuminaemia were the commonest laboratory defects at presentation. Antibody testing for coeliac disease was always negative. Variable degrees of duodenal villous atrophy were present in 98% of patients, while increased intra-epithelial lymphocytes were documented in only 65% of cases. After discontinuation of olmesartan, all reported patients achieved resolution of signs and symptoms. CONCLUSIONS: Although the available evidence is limited, the olmesartan-associated sprue-like enteropathy may be considered as a distinct clinical entity, and should be included in the differential diagnosis when serological testing for coeliac disease is negative.

Levothyroxine absorption in health and disease, and new therapeutic perspectives.

Levothyroxine therapy is used in case of deficiency of the thyroid hormones in the human organism. Many conditions, either physiological or paraphysiological or clearly pathological, can alter the levothyroxine absorption in the human body. Levothyroxine absorption can indeed be impaired by age, patient's compliance, fasting, the intake of certain foods (such as dietary fibers, grapes, soybeans, papaya and coffee) or by some drugs (such as proton-pump inhibitors, antacids, sucralfate, et cetera). Additionally, many gastrointestinal diseases, such as the conditions that disrupt the integrity of the intestinal barrier and the diseases that impair gastric acidity, may alter the bioavailability of levothyroxine. Since the enormous, widespread diffusion of thyroid diseases, a large number of patients have to face such issues. Therefore, the development of new levothyroxine oral formulations, other than solid tablets, may represent an interesting therapeutic approach, at the same time simple and effective, to face this problem. Recently, two different levothyroxine formulations have been proposed: the liquid formulation and the softgel formulation. Such formulations represent an innovative, effective and cheap therapeutic approach to hypothyroid patient with problems of impaired absorption of levothyroxine.

Intestinal gas production and gastrointestinal symptoms: from pathogenesis to clinical implication.

Intestinal gases are the expression of metabolic activity of gut microbiota in the gut, particularly carbohydrates in the case of H2, CH4. Alterations in composition of gases and air handling, directly or upon challenge with food are relevant for GI and extra-GI diseases. Assessing gas composition in breath can be a very useful tool for clinic, but technical issues are crucial (breath sampling, storing and analyzing). Aim of the present review is to summarize the understanding of the importance of intestinal gases in gastro-intestinal physiology and patho-physiology. Practical considerations on how to collect samples and instruments available for the clinic have also been provided.

La ruptura de ventrículo izquierdo como complicación del reemplazo valvular mitral / The rupture of the left ventricle as complication of mitral valve replacement

La ruptura del ventrículo izquierdo una complicación rara. Los autores analizan la frecuencia de la ruptura del ventrículo izquierdo como complicación fatal de la cirugía en el Servicio de Cirugía Cardiovascular del Hospital Universitario de Caracas, se afectuaron 534 reemplazos mitrales como procedimiento único; se encontraron 9 casos de ruptura del ventrículo izquierdo con 1 sobre vida, lo cual da una mortalidad del 88.8%. Otros autores reportan cifras entre el 35 y 100% de mortalidad cuando se produjo el accidente. Se recomienda una buena selección de la prótesis a implantar y el tamaño no debe ser demasiado grande; igualmente son preferibles las prótesis, ya sean mecánicas o biológicas de bajo perfil, especialmente en los casos en que el ventrículo izquierdo es pequeño