Efficacy and tolerability of a novel galactomannan-based formulation for symptomatic treatment of gastroesophageal reflux disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Proton Pump Inhibitors (PPIs) and traditional antacids are the common standard set of therapy for the management of gastroesophageal reflux disease (GERD) symptoms. The aim of the current study was to evaluate efficacy and safety of a novel galactomannan-based liquid formulation in reducing typical GERD symptoms in patients not taking PPIs. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, placebo-controlled study. Sixty patients met the eligibility criteria and were treated either with the investigational product (RefluG™) or placebo, one sachet three times per day for 14 consecutive days. Symptom intensity/frequency and quality of life were assessed over the course of the study by Reflux Disease Questionnaire (RDQ) and GERD-Health related Quality of life (HRQL) Questionnaire, respectively. The primary endpoint was to determine the number of subjects with at least 30% symptoms reduction from baseline to day 14 compared to placebo. RESULTS: RefluG™ was statistically superior to placebo (p <0.001) as 100% of subjects experienced at least 30% symptoms reduction at the end of the study while none achieved a 30% reduction in the placebo group. For all domains both after 7 and 14 days of treatment, significant improvement in HRQL was seen in the active group in comparison to placebo. Tolerability and safety were good and comparable between groups. CONCLUSIONS: The investigational product was safe and effective as mono-therapy in providing early resolution of troublesome GERD symptoms as well as for improving quality of life.

Severe ulcerative colitis: predictors of response and algorithm proposal for rescue therapy.

BACKGROUND: There is no agreeing if rescue therapy can avoid short-term colectomy in patients treated for severe steroid-refractory ulcerative colitis. AIMS: The aim of our study was to identify predictors of response to infliximab and cyclosporine A. METHODS: In this cross-sectional study, 49 patients with severe ulcerative colitis were included. Response to therapy was defined as three or more point reductions in Mayo score after 6 months of treatment and avoidance of colectomy after 1 year. The predictors analysed were gender, age, time from ulcerative colitis diagnosis, months of steroid or/and azathioprine therapy before onset of the severe phase, smoking habits, extension of the disease, laboratory analyses and Mayo score. RESULTS: Patients treated with infliximab showed a statistically significant higher response rate in case of moderate Mayo score (P = 0.04). Ex-smokers had very low chance of response to infliximab (P = 0.03). In the group treated with cyclosporine A, patients with C-reactive protein >3 mg/L had a response rate significantly higher than those with C-reactive protein <3 mg/L (P = 0.03); those with negative C-reactive protein and moderate Mayo score did not responded to therapy, while in the ones with elevated C-reactive protein and/or severe Mayo score, 15 versus 4 responded (P = 0.008). CONCLUSIONS: Our data suggest that cyclosporine A is advisable in ex-smokers. In never smokers or active smokers, infliximab can be prescribed in case of Mayo score ≤10 and/or negative CRP, while cyclosporine A is indicated in case of Mayo score >10 and positive CRP.

[Diagnosis and treatment of Helicobacter pylori infection in pediatrics: recommendation for 2014 clinical practice]. / Diagnosi e terapia dell'infezione da Helicobacter pylori in pediatria: raccomandazioni per la pratica clinica del 2014.

Helicobacter pylori (H. pylori) infection is a large worldwide infection usually acquired during childhood, whose prevalence in pediatric population varies, with lower incidence rates in developed countries compared to developing countries (up to 10-15% and 70%, respectively). Diagnosis can be performed both with endoscopic-based methods and noninvasive diagnostic tests, such as urea breath test and fecal antigen. Current guidelines recommend endoscopic evaluation of the young patients, in order to determine the underlying cause of abdominal pain. Even in case of suspected functional pain, patient should not be investigated for infection, unless upper endoscopy is performed to rule out organic causes. Nowadays, in pediatric population, applications of noninvasive tests are limited to verifying eradication after therapy and to investigating the presence of infection in asymptomatic patients with first-degree relatives affected by gastric cancer. Since correlation between abdominal pain and H. pylori gastritis, in absence of peptic ulcer disease is still debated, "test and treat" strategy is not recommended in children. As for adults, treatment regimens are based on the combination of proton-pump inhibitor and two or more antibiotics, for 7-14 days, depending on resistance rates of geographic areas.

Endoscopic ultrasound in the preoperative staging of gastric cancer: key messages for surgeons.

Gastric cancer (GC) remains a frequent and important cause of cancer mortality worldwide. Many factors affect the prognosis of GC, but invasion and metastasis are the leading causes of death. Due to the various stage-oriented therapies available, after the diagnosis of GC it is important to determine the staging preoperatively in order to choose the appropriate management. GC staging is the workhorse of endoscopic ultrasound (EUS). EUS can distinguish the different wall layers of the gastrointestinal tract as well as assess regional lymph nodes. Furthermore, samples of suspicious lesions or lymph nodes can be obtained by means of EUS-guided fine-needle aspiration (EUS-FNA). In this narrative review, we highlight the current status of the usefulness of EUS for GC staging, with focus on early GC that still remains a diagnostic and therapeutic challenge. In particular, the possibility to ameliorate the accuracy of EUS, in this context, by using instruments with increased ultrasound frequency is emphasized.

Endocrine manifestations of chronic HCV infection.

Chronic hepatitis C virus (HCV) infection has been associated with a great number of extra-hepatic manifestations (EHMs), including several endocrine disorders. Currently available epidemiological, clinical and experimental data do not show a link between HCV and all EHMs. Thyroid disorders (TD) and type 2 diabetes, for example, are the most frequent endocrine alterations in patients with chronic HCV infection, but there are only weak evidences that HCV could be involved in hypothalamic-pituitary axis perturbation, bone metabolism alteration and sexual dysfunctions induction. Thus, this issue needs further investigation. Prospective studies have also shown that interferon (IFN)-based therapy for chronic HCV infection can induce or worsen EHMs. In particular, IFN has been associated with development of autoimmunity and/or TD in up to 40% of chronic HCV infected patients. Hence, a careful monitoring of thyroid function should be performed in such patients. The recent approval of direct-acting antiviral agents in IFN-free regimens for chronic hepatitis C treatment will dramatically reduce not only liver-related mortality but also morbidity due to EHMs.

MicroRNAs in HBV-related hepatocellular carcinoma: functions and potential clinical applications.

Hepatitis B virus (HBV) infection is still a relevant problem worldwide and many cases of hepatocellular carcinoma (HCC) are related to HBV. The prognosis of HBV-related HCC is poor, particularly for advanced stage diagnosis. Although follow-up strategies were adopted for patients at risk, there is need for an optimal early biomarker for the screening purpose. MicroRNAs (miRNAs) are small non-coding RNAs, tightly connected to cell type and differentiation status and act as genetic regulator which can be involved in oncogenic processes. The alteration in miRNA expression pattern may represent a new opportunity for HBV-related HCC diagnosis and therapies. Some studies focused on miRNA polymorphism responsible for HCC susceptibility; others found several miRNAs deregulated by HBV X protein as well as miRNAs altered in HBV-related HCC tissue and cells. A high variability among results emerged, probably due to different techniques employed, biological substrates, experimental procedures, criteria of miRNAs selection and ethnic provenience of the included patients. Interestingly, circulating miRNAs have been studied as potential HCC-biomarkers but the reported accuracy is still not convincing, particularly in distinguishing patients with HCC from patients with cirrhosis. Hence, the use of miRNAs remains in an experimental phase and more studies are required to define their role in the clinical practice.

Chronic hepatitis B therapy: available drugs and treatment guidelines.

There are currently several drugs approved for the treatment of chronic hepatitis B including recombinant interferons, such as interferon-α and its pegylated formulation, and the nucleos(t)ide analogues, such as lamivudine, adefovir, telbivudine, entecavir and tenofovir. Pegylated-interferon is an immune-modulatory agent that works mainly by enhancing the innate immune response while nucleos(t)ide analogues are oral drugs with direct inhibition of viral replication. Each agent has its own advantages and drawbacks. Pegylated-Interferon treatment has a finite duration without induction of drug resistance but only a limited number of patients achieve a sustained virological response to therapy. On the other hand, the care with nucleos(t)ide analogues requires a long-term treatment with a potential risk of induction of drug resistance, but higher rates of viral replication suppression are achieved. Nevertheless, second generation nucleos(t)ide analogues, such as Entecavir and Tenofovir, have both high genetic barrier to resistance and potent antiviral action. This review describes the mechanisms of antiviral activity and the efficacy of viral suppression of the different available drugs for chronic hepatitis B treatment, considering the recent clinical guidelines for an optimal management of chronic HBV infection.

Gastrointestinal damage by non-steroidal anti-inflammatory drugs: updated clinical considerations.

Gastrointestinal (GI) damage by non-steroidal anti-inflammatory drugs (NSAIDs) is an important Public Health problem due to morbility and elevated mortality rate. The logic behind the development and sale of molecules which are selective cyclooxegnase-2 (COX-2) inhibitors called coxibs, is to limit the undesired effects of traditional NSAIDs, which should theoretically derive from the inhibition of COX-1. With respect to the emphasis of the initial trials, to now epidemiological studies, open-label studies, meta-analyses and reviews of the same data with longer follow-up, have produced opposite conclusions. Indeed, a recent series of meta-analyses has shown that the risks of GI events are similar for coxib and diclofenac, while they are significantly higher during the assumption of ibuprofen or naproxen. Moreover, the presumed lower gastrolesivity of coxibs is based on a highly simplified hypothesis, that the gastroprotective PGs derive from COX-1 and that the phlogistic processes are related to COX-2. Also in geriatric populations, though less tolerated than coxibs, diclofenac presents minor GI side effects when compared with naproxen and ibuprofen. In this context, in the case of moderate pain intensity, it is possible to use combinations with weak opioids, such as paracetamol-tramadol. Though intestinal damage by NSAIDs are a nosological entity of growing interest, to now no trial has been conducted with optimal criteria to demonstrate the superiority of coxibs over traditional NSAIDs. For this reason, chronic inflammation of the intestine still represents a contraindication to the administration of coxibs.

Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.