Giulia Pignataro

-Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection.

Background : Standard anti‐Helicobacter pylori therapy may not achieve a satisfactory eradication rate. Fluoroquinolones, such as moxifloxacin, are safe and promising agents for H. pylori eradication.

Helicobacter pylori eradication rate and glycemic control in young patients with type 1 diabetes

Objectives: Eradication of Helicobacter pylori is more difficult in adult patients with diabetes than in patients with dyspepsia. It has also been suggested that eradication of H. pylori in children with type 1 diabetes mellitus improves their metabolic control. The aim of the current study was to assess the eradication rate of a standard triple therapy and its effects on glycemic control in young patients with type 1 diabetes. Methods: The authors enrolled 29 type 1 diabetic patients with H. pylori, 29 type 1 diabetic patients without H. pylori, and 29 dyspeptic children with H. pylori. Groups were matched for gender and age and had similar geographical origin and socioeconomic status. H.pylori status was investigated before and 6 weeks after therapy by 13C-urea breath test. All enrolled patients with H. pylori were prescribed a standard triple therapy for eradicating H. pylori. Glycosylated hemoglobin A and daily insulin requirement were evaluated at enrollment and 6 months later in all patients with diabetes. The prevalence of the most common gastrointestinal symptoms also was investigated by means of a questionnaire in all subjects at enrollment and 6 months later. Results: Eradication of H. pylori was similar in patients with diabetes (24/29) and those with dyspepsia (23/29) (83%v 79%; P = NS). No difference in metabolic control was observed before or after antibiotic treatment in the patients who experienced H. pylori eradication. No difference in glycemic control was observed after 6 months of follow-up. Conclusions: The eradication rate of H. pylori infection was similar for young patients with type 1 diabetes and those with dyspepsia and did not improve metabolic control in a short-term follow-up.

Treatment of H. pylori Infection: A Review

Helicobacter pylori infection has been indicated as the main pathogenic factor in the development of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although the vast majority of infected subjects do not carry but a mild, asymptomatic gastritis, still there are some cases in which the eradication of the infection appears mandatory. This review addresses current anti-Helicobacter regimens and pharmacological resources, and highlights the pros and cons of each of them, according to the most recent and reliable clinical trials. Also, basic recommendations are given, regarding treatment choice in the event of the failure of a first or second line eradicating strategy, and about the implementation of standard regimens with newer antibacterial devices as probiotics.

Steatohepatitis during methylprednisolone therapy for ulcerative colitis exacerbation

Dear Sir, The occurrence of nonalcoholic fatty liver disease is a well-known side-effect of steroid therapy [1, 2]. In particular, treatment with high doses of glucocorticoid has been related to liver steatosis and more recently to nonalcoholic steatohepatitis (NASH) [3, 4]. We report a case of steatohepatitis induced by methylprednisolone therapy in a patient with an exacerbation of ulcerative colitis (UC). A 25-year-old man with a 10-year history of UC was admitted for the occurrence of bloody diarrhoea (8–10 bowel movements a day) and abdominal pain. Examination showed abdominal tenderness. Three stool cultures for parasites and bacteria were negative. Blood examinations showed normal ALT (32 U L; normal values 5–45) and AST (27 U L; normal values 10–45), and increased ERS (45 mm, normal values <10 mm) and C reactive protein (CRP-22 ng mL; normal values <5 ng mL). An abdominal ultrasound examination was then performed with no evidence of liver diseases. Colonoscopy showed left colitis with marked mucosal hyperaemia with small punctate ulcers, and biopsies showed severe chronic inflammation with presence of multiple crypt abscesses, epithelial flattening and ulceration consistent with UC exacerbation. Methylprednisolone therapy 40 mg day showed an improvement in symptoms within a few days with two daily bowel movements of formed stool without blood. Then he was dismissed. Therapy was tapered to 16 mg in 4 weeks. After 40 days blood examination showed an increase in ALT value (106 U L). AST remained normal (41 U L). ERS and CRP were normal (8 mm at first hour and 3 ng mL, respectively). An abdominal ultrasound examination was then repeated with the evidence of fat infiltration consistent with liver steatosis. Hepatitis virus (HAV, HBV, HCV, HEV, HGV, CMV and EBV) and antibodies against mitochondria, smooth muscle and nuclear antigens were not detected by serological tests. Liver biopsy showed macrovescicular hepatocellular fat accumulation, periportal inflammation and mild fibrosis (Fig. 1). The patient denied a history of alcohol abuse and the intake of hepatotoxic drugs and a diagnosis of nonalcoholic steatohepatitis was made [5]. He stopped the steroid treatment in 2 weeks and ALT value gradually decrease to normality. An abdominal ultrasound examination performed after 3 months showed an improvement in liver morphology with reduction in fat infiltration. Serological test for virus and autoantibodies were retested in the hypothesis of previous false negative results due to steroid therapy and were confirmed negative. The patient refused to participate in a second liver biopsy. After 6 months abdominal ultrasound showed a normal liver. Now, he is in remission with a 5-ASA maintenance therapy, with normal values of ALT and AST. Previously, steroid treatment has been related to steatohepatitis and fatal liver failure in two patients affected by systemic lupus erythematosus [3] and in our case steatohepatitis appears after starting steroid treatment in UC. Although drug discontinuation seems effective to induce remission of this condition a careful follow-up of patients submitted to steroids has to be performed because of the possibility of development of liver failure.

Prospective evaluation of epidemiological, clinical, and microbiological features of pandemic influenza A (H1N1) virus infection in Italy

Since several characteristics of pandemic influenza A (H1N1) virus infection remain to be determined, this study aimed to describe clinical features and complications of patients infected with H1N1. Subjects affected by influenza‐like illnesses and a control group of asymptomatic patients were enrolled prospectively at an Emergency Department from October 2009 to April 2010. At enrollment, clinical data and nasopharyngeal swabs for virological analyses were obtained. Ill subjects were followed until recovery and swabs were collected weekly in patients infected with H1N1. Of 318 patients enrolled, 92 (28.9%) were positive to H1N1. Patients infected with H1N1 were mainly young adults and complained classic influenza‐like symptoms. Fever was observed for a median time of 5 (IQR 3–7) days. Hospitalization occurred in 27.7% with 2% requiring intensive care unit admission: median length of hospitalization was 6 days (IQR 5–9). Pneumonia was diagnosed in 19.6% of patients. A similar proportion of lower airways involvement and of clinical complications was observed in subjects testing positive or negative for H1N1. However, patients infected with H1N1 were younger and hospitalized for a shorter period as compared to the control group (P = 0.002 and P = 0.045, respectively). Older age, asthma/chronic obstructive pulmonary disease and hypertension were associated with an increased risk of pneumonia. Viral shedding was observed for at least 1 week in 21.3% of patients. Asymptomatic infection was uncommon (1.1%). Respiratory syndromes caused by H1N1 and factors associated with disease severity were investigated and compared to influenza‐like illnesses of other origin. Such findings might contribute to improve clinical and epidemiological management of the disease. J. Med. Virol. 83:2057–2065, 2011.

Idiopathic Thrombocytopenic purpura and Helicobacter pylori Infection

TO THE EDITOR: Idiopathic thrombocytopenic purpura (ITP) is a haematologic autoimmune disease associated with several chronic infections (HBV and HCV chronic hepatitis, HIV). Recent studies investigating the association of Helicobacter pylori gastric infection and ITP, however, have shown conflicting results, but even negative study suggests that at least a small group of patients with ITP could benefit from eradication of H. pylori. A 41-year-old man with a previous diagnosis of ITP was referred to our department for the clinical appearance of spontaneous haemorrhagic manifestation (petechiae and conjunctival haemorrhage). He had a 1-year history of low platelet count ( 50000/cmm) found by chance during a routine control 1 year prior to admission to our hospital. It was for this reason that he was admitted to the Dept. of Haemotology, where thrombocytopenia was confirmed and where a diagnosis of ITP was made (platelet count of 12000/ cmm; normal morphology with count above normal value of megakaryocytes at bone marrow aspiration; presence of antiplatelet-associated antibodies (PAIgG)). The patient denied previous consumption of drugs. No other causes of thrombocytopenia were found and he was started on therapy with prednisone 1.5 mg/kg/day, but without improvement of platelet count (18000/cmm after 15 days and 21000 after 2 months of therapy). Splenectomy was then proposed but the patient would not consent. He was dismissed with the diagnosis of ITP and continued corticosteroids for 2 months without any effect on platelet count. When he was admitted to hospital we decided, on the basis of recent data, to explore the occurrence of an infection. Serology for hepatitis B and C viruses and for HIV was performed and resulted negative. Moreover, nuclear antibodies, antiphospholipid and immunoglobulin serum levels were performed to investigate the presence of systemic diseases related to thrombocytopenia such as IgA deficiency, common variable hypogammaglobulinaemia, systemic lupus erythematosus and the antiphospholipid syndrome. Although the patient did not present gastrointestinal symptoms, a urea breath test performed for H. pylori detection resulted positive. Endoscopy was therefore performed and the presence of H. pylori was confirmed by histology. Serology showed that he was affected by the more virulent Cag-A positive strain (123 IU/mL; normal value 20 IU/mL) and positivity to PAIgG was confirmed (204 ng/10 cells; normal values 10 ng/10 cells). He started therapy with amoxycillin 1 g b.i.d., clarithromycin 500 mg b.i.d. and rabeprazole 20 mg b.i.d. for 7 days. After 30 days the urea breath test was repeated and resulted negative. At this time, and again after 6 months, platelet count, serum antibodies anti-Cag-A and antibodies anti-platelet counts were repeated. Platelet count increased progressively to normality, while on the contrary serum Cag-A antibodies and serum PAIgG values decreased at 1 month and completely disappeared after 6 months. Now, 1 year after eradication treatment, his platelet count is still normal. Similar reports of an association between H. pylori infection and idiopathic thrombocytopenic purpura are available in the literature (1–8). In a small case series of patients affected by ITP and H. pylori gastric infection, our group first reported an improved platelet count and normalization of serum titre of antiplateletassociated antibodies after H. pylori eradication (1). More recently, two larger studies have been published in an attempt to clarify this issue (2, 3). Emilia et al. studied 30 patients with ITP and found 13 to be H. pylori-positive. Four patients showed a complete response of thrombocytopenia after eradication of H. pylori. These authors concluded that H. pylori eradication could be a new good option in the treatment of ITP (because of its low cost, simple execution and absence of side effects) (2). Jarque et al. investigated 56 patients with ITP and 13% (3 out 23) of evaluable H. pylori-positive patients showed a response to H. pylori eradication (3). Although the author concluded that his data did not support a correlation between gastric infection and ITP the differences compared to the Emilia study were small. Moreover, in the past 4 years, resolution of ITP after H. pylori eradication has been described in 4 case reports published in an international journal (5–8). Finally, another case report about resolution of ITP after omeprazole therapy could be explained by the batteriostatic effect of this drug on H. pylori. These data suggest that H. pylori infection is associated with at least some ITP patients. The pathogenic mechanism proposed linking H. pylori to thrombocytopenia is the cross mimicry between platelets and bacterial antigens (9). A recent report of our group demonstrating a cross-reaction between antibodies to Cag-A and platelet proteins seems to confirm this hypothesis (10). In our patient, the titre of Cag-A antibodies decreased similarly to antiplatelet associated autoantibodies. In conclusion, our report confirms that H. pylori could have an important role in ITP and that before considering invasive or toxic treatment (splenectomy, immunosuppressant drugs) H. pylori should be tested and eventually eradicated. The possibility that H. pylori and in particular Cag-A positive strains might induce thrombocytopenia should be further investigated. CORRESPONDENCE

Anti‐Saccharomyces cerevisiae antibodies and coeliac disease

Anti-Saccharomyces cerevisiae antibodies (ASCA) have been used as serological markers to differentiate between Crohn disease and ulcerative colitis (1). ASCA are clinically useful when associated with ANCA in predicting evolution of indeterminate colitis to Crohn disease or ulcerative colitis and in paediatric inflammatory bowel disease, in which non-invasive diagnostic tests are desirable (2). ASCA positivity is related to Crohn disease and especially with small-bowel involvement (1). ASCA prevalence has therefore been studied in intestinal diseases such as coeliac disease. A recent report showed a high prevalence of ASCA in coeliac disease (3). The aim of our study was to evaluate ASCA prevalence in coeliac patients on a gluten-free diet and in patients with Crohn disease with small-bowel involvement.

Relationship between gastric localization of hepatitis C virus and mucosa-associated lymphoid tissue in Helicobacter pylori infection.

Background: Hepatitis C virus (HCV) has been localized in several extra-hepatic sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localization of HCV and its possible relationship with the chronic inflammatory response to Helicobacter pylori infection. Methods: Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutively enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inflammatory infiltrates (classified as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobulin heavy-chain (IgH) gene rearrangements of mucosal B cells. Results: In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach ( P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was significantly associated with marked or moderate inflammatory infiltrates. Oligoclonal IgH gene rearrangements were detected in three group A patients who harboured both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to find HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals. Conclusions: HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inflammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells.

Sonographic Detection of Spontaneous Pneumomediastinum

Spontaneous pneumomediastinum is an uncommon benign disease that mainly affects young, tall, and thin male patients without evidence of trauma or other underlying pulmonary disease. It is a condition caused by an increase of intrathoracic pressure and air leaking from the trachea, bronchi, alveoli, or esophagus into the mediastinum. Although it is often a self-limiting disease, it requires admission to a hospital to exclude potentially severe underlying diseases. 1 In healthy individuals, it has been related to vomiting, pregnancy, singing, physical efforts, cocaine or ecstasy (3,4-methylenedioxy-N-methylamphetamine) use, and scuba diving. Diagnosis of pneumomediastinum is generally performed by means of chest radiography, but in up to 30% of cases that may be not diagnostic, particularly in emergency settings, 2,3 and computed tomography (CT) may be needed to confirm the diagnosis. We report a case of self-resolving spontaneous pneumomediastinum that was missed by chest radiography in which the diagnosis was suggested by neck sonography.

Evaluation of the albumin-γ-glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma-complicating liver cirrhosis

Aim: The present study aimed to evaluate the usefulness of albumin‐γ‐glutamyltransferase isoenzyme in the diagnosis of hepatocellular carcinoma.