Proton pump inhibitors: use and misuse in the clinical setting

Introduction: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia

Abnormal coronary reserve and left ventricular wall motion during cold pressor test in patients with previous left ventricular ballooning syndrome

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Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Introduction Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile. Methods In a sample of cerebral small vessel disease (SVD) patients, we assessed MCI subtypes distributions according to different operationalization of Winblad criteria and compared the neuroimaging features of single versus multidomain MCI. We applied three MCI diagnostic scenarios in which the cutoffs for objective impairment and the number of considered neuropsychological tests varied. Results Passing from a liberal to more conservative diagnostic scenarios, of 153 patients, 5% were no longer classified as MCI, amnestic multidomain frequency decreased, and nonamnestic single domain increased. Considering neuroimaging features, severe medial temporal lobe atrophy was more frequent in multidomain compared with single domain. Discussion Operationalizing MCI criteria changes the relative frequency of MCI subtypes. Nonamnestic single domain MCI may be a previously nonrecognized type of MCI associated with SVD

Complexity and diversity of gastroesophageal reflux disease phenotypes

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome

Drugs for improving esophageal mucosa defense: Where are we now and where are we going?

In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients. In this review we will summarize the existing knowledge of the old and novel compounds able to produce this therapeutic effect, including sucralfate, alginate-based drugs, and a new medical device consisting of hyaluronic acid and chondroitin sulfate dispersed in a bioadhesive carrier, together with the potential indications for their use. It is to be stressed, however, that, although these compounds may represent a real alternative to PPI therapy in GERD, the combination of mucosal protection with acid suppression may help manage many cases with a partial or unsatisfactory response to PPIs alone

Long-Term Follow-Up Study of Liver-Related Outcome After Bilio-Pancreatic Diversion in Patients with Initial, Significant Liver Damage

Background: Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis. Aims: To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage. Methods: This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5 years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score. Results: During a median follow-up of 78 months, median weight decreased from 119 to 78 kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0 kg/m2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from 12 0.929 ( 12 1.543 to 12 0.561) to 12 1.609 ( 12 2.056 to 12 1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%). Conclusions: Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion