Giuseppe Merra

High dosage rifaximin for the treatment of small intestinal bacterial overgrowth

Rifaximin is a broad spectrum non‐absorbable antibiotic used for treatment of small intestinal bacterial overgrowth. Doses of 1200 mg/day showed a decontamination rate of 60% with low side‐effects incidence.

Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed?

OBJECTIVES:Impaired intestinal permeability (IP) may have a role in the pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC patients with respect to healthy controls.METHODS:IP was evaluated by the 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) permeability test in 52 LC patients and in 48 sex- and age-matched controls. The presence of 51Cr-EDTA was also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients with ascites.RESULTS:An altered IP was found in 45% of LC patients compared with 4% of controls (P<0.00001). IP impairment was significantly associated with Child–Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A patients), with the presence of ascites (60% in ascitic patients vs. 31% in nonascitic patients), and with a history of SBP (100% of patients with SBP vs. 50% of those without SBP). 51Cr-EDTA was present in all ascitic samples obtained from patients with SBP compared with 22% of patients without SBP.CONCLUSIONS:IP derangement was a common finding in LC, especially in patients with more advanced disease (presence of ascites and history of SBP). The presence of 51Cr-EDTA in ascites in patients with SBP suggests an altered permeability of splancnic vessels and/or peritoneal membranes. Further studies are required to assess 51Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies.

Coronary atherosclerotic burden in patients with infection by CagA-positive strains of Helicobacter pylori

ObjectivesCytotoxic associated gene-A (CagA)-positive strains of Helicobacter pylori emerged as a possible atherosclerotic stimulus. Nevertheless, whether CagA-positivity is associated with more extensive or severe atherosclerotic coronary burden has never been studied. MethodsForty consecutive patients with coronary artery disease (CAD) and twenty consecutive patients with normal coronary arteries undergoing coronary angiography were enrolled. All patients underwent evaluation of classical atherogenic risk factors and assessment of anti-urease B and anti-CagA antibodies titer. Either the severity of coronary stenosis (stenosis score) or the extent of coronary atherosclerosis (extent score) was evaluated in CAD patients. ResultsThe anti-CagA antibody titer was significantly higher in patients with CAD as compared with normal coronary arteries patients [85 (10–108.75) vs. 47.3 (17–64) RU/ml, P=0.02], whereas there were no differences in anti-urease B titer between the two groups. A significant correlation was found between anti-CagA antibody titer and extent score (R=0.35, P=0.03), whereas stenosis score was similar (R=0.25, P=0.11). On the contrary, no significant correlation was found between anti-urease B antibody titer and either extent or stenosis score. Moreover, CagA-positive patients had a more extensive CAD (P=0.029) when compared with CagA-negative patients. Interestingly, whereas serum glucose, LDL levels, anti-urease B, and anti-CagA antibodies were predictors of extent score at univariate analysis, at multivariate analysis anti-CagA antibody titer only was an independent predictor of the extent of coronary atherosclerosis (B=0.051, standard error of B=0.042, P=0.04). ConclusionThese results support the association between CagA-positive H. pylori infection and coronary atherosclerotic burden. Further studies are needed to better elucidate the mechanism by which CagA-positive strains may promote atherosclerosis.

Celiac Disease: What’s New about It?

In the present review we will try to summarize the clinical and diagnostic features of celiac disease (CD) as well as the new findings on extraintestinal manifestation. CD is an immune-mediated enteropathy caused by a permanent gluten intolerance. In the last years, the diagnosis is becoming more and more frequent because of the recognition of ‘new’ symptoms and associated extraintestinal manifestations. Classical CD is dominated by symptoms and sequelae of gastrointestinal malabsorption. In the ‘atypical forms’, the extraintestinal features usually predominate, with few or no gastrointestinal symptoms. Silent CD refers to asymptomatic patients with a positive serologic test and villous atrophy on biopsy. This form is detected by screening of high-risk individuals, or villous atrophy occasionally may be detected by endoscopy and biopsy conducted for another reason. The potential form is diagnosed in groups at risk including relatives of celiac patients, Down syndrome and autoimmune diseases. Latent CD is defined by positive serological tests but not histological changes on biopsy. These individuals are asymptomatic, but later may develop symptoms and/or histological alterations. Recognition of atypical manifestations of CD is very important because many cases can remain undiagnosed with an increased risk of long-term complications.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

AIM To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. METHODS Patients suffering from mild to moderate ulcerative colitis (UC) or Crohns disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. RESULTS All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. CONCLUSION PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients.

Primary autoimmune haemolytic anaemia and coeliac disease

The clinical spectrum of coeliac disease (CD) is widely variable, from the classic malabsorption syndrome to the atypical and the silent forms (1). Epidemiological studies using highly sensitive and specific serological markers for CD, i.e. the anti-transglutaminase (tTG) and antiendomysium (AEA) antibody tests, found CD to be highly common in Europe (0.33%) (2). Because CD is often asymptomatic, the detection rate can be strongly increased by serology (2). Autoimmune disorders (including insulin-dependent diabetes, thyroid disease, autoimmune liver disease, cardiomyopathy) are ten times more common in patients with CD than in the general population. When both autoimmune disease and CD occur in a patient, CD is often silent, the autoimmune disorder being usually diagnosed first (1). The mortality risks are significantly elevated in CD patients for a wide array of diseases, including non-Hodgkin lymphoma, cancer of the small intestine and autoimmune diseases (3). Miller described two patients with autoimmune haemolytic anaemia (AIHA) strongly associated with CD. He hypothesized that AIHA may represent an extension of immunological disorders linked to CD, centred on the histocompatibility antigen B8 (4). AIHA is characterized by the production of antibodies directed against self-RBCs (5). On the basis of aetiology AIHA is classified as primary and secondary (to lymphoproliferative disorders, autoimmune disorders, infections, immunodeficiency disorders and tumours) (5). To the best of our knowledge, no data on patient series investigating an association between CD and primary AIHA are available in the literature at the moment. The aim of our study was to assess the prevalence of CD in patients with primary AIHA and in a population of healthy controls.

Celiac Disease and Myointimal Proliferation: A Possible Correlation?

Celiac disease (CD) is an autoimmune disorder of the small bowel that occurs in genetically predisposed people of all ages, from middle infancy, and is caused by a reaction to gliadin, a gluten protein. Some patients are diagnosed with symptoms related to the decreased absorption of nutrients or with various symptoms which, although statistically linked, have no clear relationship with the malfunctioning bowel. Classic symptoms of CD include diarrhea, weight loss, and fatigue; bowel symptoms may be limited or even absent. In this article we describe the case of a young woman with CD who presents with myointimal proliferation. However multiple cases of vessel thrombosis have been reported in patients with CD. Despite the fact that no definitive relationship between these diseases could be explained, we think this association must be remembered especially in cases of young and tenuous women with these vascular abnormalities.

Effects of Exenatide on both fat mass loss and cardiometabolic risk in obese subjects with type 2 diabetes mellitus

Objective: The regulation of glucose and adipose tissue metabolism by GLP1-receptor agonist is a possible treatment of T2D and obesity. These new pharmacologic agents target insulin resistance and metabolic disorders. Methods: Eighteen patients, 7 males and 11 females, were studied with T2D, divided into two groups: the first (I) was poorly controlled by metformin and sulfonylureas; the second (II) was treated only with metformin. Exenatide was administered at an initial dose of 5 μg twice a day for one month, and then the dose was adjusted to 10 μg twice a day throughout 24-26 weeks. From the beginning of therapy, each group was analyzed at time 0 and at 1 month (T1) and then 6 months (T2). At every time, anthropometric data, body composition by DXA and biochemical parameters were recorded. Results: At baseline, all patients enrolled showed metabolic disorders and obesity. The comparison of both groups between baseline and T2 showed a significant decrease of body weight, total Fat Mass (FM) and HbA1c (%), only in group (I) a statical reduction of Glycaemia and Total Cholesterol was observed. The Free Fat Mass (FFM) was never seen significantly different. The patients with HbA1c levels >75 mmol/mol (9%) at baseline showed a greater decline of HbA1c when compared to the patients with HbA1c <75 mmol/mol. Conclusion: Exenatide improves glucose metabolism and total cholesterol levels. Moreover, Exenatide reduced total FM and did not affect FFM. Exenatide could be used to treat obesity in diabetic but also non-diabetic patients. Summary: Exenatide, a GLP1-receptor agonist, is a pharmacological agent against obesity and type 2 diabetes mellitus. Exenatide decreases insulin resistance and lipids metabolism, and could be able to reduce fat mass and cardiovascular risk.

Splenomegaly as a Primary Manifestation of Gaucher Disease in a Young Adult Woman

Gaucher disease is the most common lysosomal storage disease. It is caused by the defective activity of acid β-glucosidase, which results in the accumulation of lipid glucocerebroside in macrophages throughout the body. In this case report we describe the case of a young adult woman with splenomegaly as the primary manifestation of this pathology. This is a case of type 1 Gaucher disease because there is a lack of primary neurological involvement but we have, instead, an age-independent involvement of the visceral organs. It is very important to classify or characterize these patients in a precise manner and to make a complete diagnosis with the help of the many diagnostic resources now at our disposal, especially with genetics, radiology and new techniques of advanced microscopy, also because Gaucher disease requires a long and complex management from early life to adulthood.