Annalisa Tortora

Helicobacter pylori and extragastric diseases.

While Helicobacter pylori infection was initially revealed to be associated only with some gastroduodenal diseases, further studies have shown its possible role in several extragastric diseases. For idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency, the diagnosis of H. pylori infection is recommended, and there are many other conditions such as cardiovascular, neurological, dermatological, and respiratory diseases in which H. pylori may possibly play a role. Interestingly, a potential role has also been described for GI neoplastic diseases, including colorectal and pancreatic cancer. Different mechanisms of action have been proposed, ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic over the last year.

The role of small intestinal bacterial overgrowth in Parkinson's disease

Parkinsons disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty‐three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinsons Disease Rating Scale–IV and by 1‐week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half‐emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed‐on and no‐on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%.

Gut microbiota and metabolic syndrome

Symbiosis is the result of the relationship between gut microbiota and human surfaces; in fact, it regulates many functions such as metabolic and protective ones. It is widely known that any changes in the microbes in gut microbiota (dysbiosis) and the regulation of mucosal and systemic host’s immunity have been linked to different diseases such as metabolic syndromes and associated disorders. Recent studies report an aberrant gut microbiota and an alteration of gut microbial metabolic activities in obese subjects, with an important influence of a number of human physiological functions. Most studies suggest that diet, especially the high-fat low-fiber western-style diet, dramatically impacts on gut microbiota composition and functions in those patients with metabolic syndrome. A deeper knowledge of a specific microbiota profile associated with increased risk of metabolic disease and its subsequent modification induced by prebiotics, probiotics or targeted antibiotics will be necessary for the development of new therapeutic approaches in the treatment of metabolic disease.

Role of Gut Microbiota in Food Tolerance and Allergies

Alterations of commensal flora may cause various gastrointestinal and extraintestinal diseases, including food intolerances and food allergies. According to the ‘microflora hypothesis’, alterations in the composition of gut microbiota in industrialized countries have disturbed the mechanisms of mucosal immune tolerance. Over the past few years several studies have looked for a role for probiotics in the treatment of food allergies with promising results.

CD133+ stem cell mobilization after partial hepatectomy depends on resection extent and underlying disease.

BACKGROUND Bone marrow stem cells (BMSC) can participate to liver regeneration. However, conflicting results have been reported on this topic in patients undergoing liver resection. AIMS To assess the impact of liver resection extent and presence of underlying liver disease in modulating BMSC mobilization. METHODS We enrolled 29 patients undergoing liver resection of different extents, 5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by flow cytometry at different time-points after surgery. The hepatic commitment of mobilized BMSC was investigated by polymerase chain reaction. Liver specimens were collected during surgery for histopathological analysis. Hepatocyte growth factor and granulocyte-colony stimulating factor serum levels were measured by enzyme-linked immunosorbent assay. RESULTS BMSC mobilization was found in patients undergoing major liver resection, especially in the presence of underlying disease. Ductular reactions were noted in patients with chronic hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM, cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte-colony stimulating factor levels increased following liver resection and the contemporaneous presence of liver disease was associated with their highest raise. CONCLUSIONS Liver repair is mainly an endogenous process. BMSC become important in case of extensive resection, especially in the presence of underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte growth factor and granulocyte-colony stimulating factor seem to be involved in the dynamics underlying hepatic regeneration and BMSC recruitment.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

BACKGROUND Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING Italian Medicine Agency.

Liquid melevodopa versus standard levodopa in patients with Parkinson disease and small intestinal bacterial overgrowth.

Objectives Patients with Parkinson disease exhibit a highly increased prevalence of small intestinal bacterial overgrowth (SIBO), which has been also associated with the severity of motor fluctuations. Aim of this study was to test the efficacy of liquid levodopa with higher bioavailability in patients with SIBO. Methods Thirty-three patients with Parkinson disease underwent both lactulose and glucose breath tests to assess the presence of SIBO. A urea breath test was performed to assess the presence of a concomitant Helicobacter pylori infection. Patients were challenged with 250 mg of levodopa and 314 mg of levodopa methylester. Drug challenges were performed on different days and at baseline and 1 month after SIBO eradication. During the tests, the motor condition and the plasma levodopa concentrations were evaluated. Results At baseline, the onset of motor benefit was significantly shorter after melevodopa than after standard levodopa, as confirmed by the latency to motor on condition and t max (time to the on condition, 28.8±11.5 vs 55.5±40.2 minutes; P=0.0004; and t max, 28.2±9.7 vs 50.0±11.0 minutes; P=0.002). The duration of the on time or area under the curve was not significantly different. The underlying gastrointestinal condition did not influence these results. Conclusions The reduction of the latency to the on condition in the absence of a reduction of the on duration is a promising feature of melevodopa because this effect would increase the total daily on duration. Future studies that evaluate the usefulness of melevodopa beyond the acute challenge (eg, using motor diaries) in patients with gastrointestinal infections are warranted.

High Dose Amoxicillin-Based First Line Regimen is Equivalent to Sequential Therapy in the Eradication of H. pylori Infection

OBJECTIVE Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy. PATIENTS AND METHODS We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed. RESULTS Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (p<0.01), while no significant differences were observed in HD-LCA group compared to LACT (p=ns). Compliance and occurrence of adverse effects were similar among groups. CONCLUSIONS High-dose amoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage.

The metabolic and toxicological considerations for mTOR inhibitors in the treatment of hepatocarcinoma

Introduction: Hepatocellular carcinoma (HCC) is a major health problem worldwide. Several molecular pathways involved in HCC growth and progression have recently been identified. Rapamycin analogs are able to inhibit one of the most active oncogenic molecular pathways in HCC cells: the mammalian target of rapamycin (mTOR) pathway. Areas covered: In this review, the authors analyze the principal molecular features of the mTOR pathway and the use of rapamycin analogs in the treatment of hepatocarcinoma. The article also looks at the reoccurrence of HCC following liver transplantation as well as after the treatment of de novo neoplasms. Finally, the authors discuss the advantage of using a combined HCC pharmacological therapy to obtain a synergistic effect on tumor mass. Expert opinion: Among the available options for the treatment of advanced-stage HCC, mTOR pathway inhibitors show great promise. Once these agents have their safety and efficacy confirmed, in the treatment of liver disease, their use should be considered in patients affected by HCC. This should especially be the case for those who have had liver transplants or suffered with de novo tumors. Moreover, the authors believe that mTOR inhibitors could be used in a combined pharmacological approach to improve HCC molecular-targeted therapy by producing a multiple-level block of tumor intracellular signaling.

Possible Radio Interference Between Video Capsule Endoscopy and Second-Generation OmniPod Patch Pump

Video capsule endoscopy (VCE) is a noninvasive diagnostic tool used to observe the small intestinal mucosa. We report a case of a 57-year-old woman with T2DM, treated with continuous subcutaneous insulin infusion using second-generation OmniPod patch pump, undergoing VCE (Given M2A; VCE Ltd, Yoqneam, Israel) for melena and anemia. During VCE, an abnormal interruption of communication between video capsule and its receiver occurred. Two hours after capsule ingestion, the patient activated the insulin pump infusion through the Personal Diabetes Manager (PDM) because she drank a sugary beverage for the first time after ingestion. Due to this, we decided to repeat VCE after the removal of the insulin pump and PDM: at this time, the capsule recorded for more than 10 h without any interruption. The video capsule and second-generation OmniPod patch pump use the same radio frequency and this may cause interference between these two devices. In patients using second-generation OmniPod patch pump undergoing VCE, we suggest to switch to intravenous insulin infusion or multiple daily injection or to use a different model of VCE, as MiRoCam (Intromedic, Seoul, Korea).