Alzheimer's disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement.

Background: Alzheimer disease (AD) is a leading cause of global burden with great impact on societies. Although research is working intensively on promising therapy, the problem remains up-to-date. Among the various proposed hypotheses regarding causality and therapy, emerging evidence supports the hypothesis that gastrointestinal microbiota through the so-called 'gut-brain axis' interacts with immune system and brain and shape the balance between homeostasis and disease; the involvement of gastrointestinal microbiota in the pathophysiology of AD is less defined, even though the role of 'gut-brain axis' has been well verified for other neurodegenerative conditions.Methods: We performed a systematic review of PubMed/MEDLINE database from 1st January 1990 to 17th October 2018, to investigate the accessible literature regarding possible association between AD and gastrointestinal microbiota. Inclusion criteria were available full text in English language, original clinical papers implicating AD patients and any sort of gastrointestinal microbiota.Results: Through our query, an initial number of 241 papers has been identified. After removing duplicates and through an additional manual search, twenty-four papers met our inclusion criteria. The great majority of eligible publications supported a possible connection between AD and gastrointestinal microbiota. The most common investigated microorganism was Helicobacter pylori.Conclusion: Our own systematic review, showed a possible association between AD and gastrointestinal microbiota mainly including Helicobacter pylori, and thus further research is required for substantiation of causality as well as for the establishment of promising novel therapies.

Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: A cost-effectiveness analysis.

INTRODUCTION: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. AIM: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. MATERIALS AND METHODS: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. RESULTS: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). DISCUSSION: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I.

Noninvasive Liver Fibrosis Tests in Patients with Nonalcoholic Fatty Liver Disease: An External Validation Cohort.

The main aim of this study was the comparative evaluation of nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), fibrosis 4 index (FIB-4), AST-to-Platelet Ratio Index (APRI), and enhanced liver fibrosis (ELF) test in distinguishing none/early (F0/F1) from significant/advanced (F2/F3) fibrosis in NAFLD patients, thereby providing an external validation cohort. Thirty-one patients with biopsy-proven NAFLD and 10 matched controls without NAFLD were prospectively enrolled. Serum hyaluronic acid (HA), aminoterminal propeptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases (TIMP)-1, and biochemical tests were measured. NFS, FIB-4, APRI, and ELF were calculated. ELF, FIB-4, and APRI, but not NFS, were higher in F2/F3 than F0/F1 group. Specifically, ELF [area under the ROC curve (AUROC): 0.86±0.10; p=0.004) and APRI (AUROC: 0.86±0.07; p=0.005], but not NFS (AUROC: 0.68±0.12; p=0.16), and FIB-4 (AUROC: 0.71±0.11; p=0.10), could similarly discriminate F0/F1 from F2/F3 stage. The sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were: a) for cut-off of APRI=0.5, 85.7%, 70.8%, 46.2%, and 94.4%, respectively, and b) for cut-off of ELF=9.0, 85.7%, 83.3%, 60.0%, and 95.2%, respectively. When ln(PIIINP) or TIMP-1 were combined with APRI, the combined AUROCs could distinguish F2/F3 from F0/F1, but without significantly higher accuracy compared with APRI alone. APRI could also distinguish patients with simple steatosis from nonalcoholic steatohepatitis, and those with from those without lobular inflammation and ballooning, findings warranting further research. In conclusions: The application of ELF test and APRI can distinguish F0/F1 from F2/F3 fibrosis stages in NAFLD patients.

Acute Liver Failure: From Textbook to Emergency Room and Intensive Care Unit With Concomitant Established and Modern Novel Therapies.

Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available.

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

BACKGROUND: Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. METHODS: We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. RESULTS: Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. CONCLUSIONS: Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease.

Effects of combined low-dose spironolactone plus vitamin E vs vitamin E monotherapy on insulin resistance, non-invasive indices of steatosis and fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized controlled trial.

The beneficial effects of mineralocorticoid receptor blockade by spironolactone have been shown in animal models of non-alcoholic fatty liver disease (NAFLD). The aim of the present 52-week randomized controlled trial was to compare the effects of low-dose spironolactone and vitamin E combination with those of vitamin E monotherapy on insulin resistance, non-invasive indices of hepatic steatosis and fibrosis, liver function tests, circulating adipokines and hormones in patients with histologically confirmed NAFLD. Homeostasis model of assessment of insulin resistance (HOMA-IR) and non-invasive indices of steatosis and fibrosis were calculated. Analysis was intention-to-treat. NAFLD liver fat score, an index of steatosis, decreased significantly in the combination treatment group (P = .028), but not in the vitamin E group, and the difference for group*time interaction was significant (P = .047). Alanine aminotransferase-to-platelet ratio index, an index of fibrosis, did not change. Insulin levels and HOMA-IR decreased significantly only within the combination group (P = .011 and P = .011, respectively). In conclusion, the combined low-dose spironolactone plus vitamin E regimen significantly decreased NAFLD liver fat score. Larger-scale trials are needed to clarify the effect of low-dose spironolactone on hepatic histology.

Impact of nitroglycerin and glucagon administration on selective common bile duct cannulation and prevention of post-ERCP pancreatitis.

OBJECTIVE: Easy common bile duct (CBD) cannulation is associated with low complication rate. This study aimed to investigate the potential impact of nitroglycerin and glucagon administration on selective CBD cannulation and prevention of post-ERCP pancreatitis. METHODS: A prospective single center, double-blind randomized study in which a total of 455 patients were randomly assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group B). After ERCP, patients were followed for the development of drugs' side-effects and post-ERCP complications. RESULTS: There were no statistically significant differences between the two groups regarding demographic data and ERCP findings. Success rate of selective CΒD cannulation was 95.15% in group A versus 82.29% in group B (p < .001). Time required for CBD cannulation was 2.82 ± 2.31 min in group A versus 4.27 ± 3.84 min in group B (p = .021). Needle-knife papillotomy was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p = .001). The frequency of post-ERCP pancreatitis was significantly lower in group A than in group B (3.08% versus 7.46%, p = .037). No difference was observed between the two groups with regard to the occurrence of post-procedure hemorrhage. There was no procedure-related mortality; no adverse event related to the combination regimen was observed. CONCLUSIONS: Combined nitroglycerin and glucagon administration achieves a high selective CBC cannulation rates with concomitant reduction of post-ERCP pancreatitis incidence. However, further relative large-scale studies are needed to confirm our findings before definite conclusions can be drawn (Clinical trial registration number: NT: 4321).

Vaspin, resistin, retinol-binding protein-4, interleukin-1α and interleukin-6 in patients with nonalcoholic fatty liver disease.

UNLABELLED:  Background and rational. Data on newer adipokines and interleukins in patients with nonalcoholic fatty liver disease (NAFLD) are inconclusive. The primary aim of this study was the evaluation of serum vaspin, resistin, retinol-binding protein (RBP)-4, interleukin (IL)-1α and IL-6 levels in NAFLD patients compared to matched controls, and their association with disease severity. MATERIAL AND METHODS: Twenty-nine consecutively enrolled NAFLD patients with histologically confirmed nonalcoholic simple steatosis (SS; n = 15) or steatohepatitis (NASH; n = 14) and 25 matched controls without NAFLD were recruited. Serum vaspin, resistin, RBP-4, IL-1α and IL-6 and biochemical tests were measured. RESULTS: Serum vaspin levels were lower and IL-6 levels higher in NASH patients than controls, but similar between controls and SS patients, or NASH and SS patients (vaspin, controls: 728.5 ± 39.3; SS: 634.6 ± 63.7; NASH: 531.5 ± 52.0 pg/mL; p for trend 0.028; IL-6, controls: 1.5 ± 0.2; SS: 2.5 ± 0.6; NASH: 3.0 ± 0.6 pg/mL; p for trend 0.032). However, after adjustment for body mass index or waist circumference, both vaspin and IL-6 did not remain significantly different between groups. Resistin, RBP-4 and IL-1α were not statistically different between groups. None of the selected adipokines or interleukins could independently differentiate NAFLD from SS, or patients with more severe from less severe histological lesions. CONCLUSION: Lower circulating vaspin, but higher IL-6 levels were observed in NASH patients than controls, whereas resistin, RBP-4 and IL-1α levels were similar between groups. However, these differences did not remain robust after adjustment for body mass index or waist circumference.

The role of capsule endoscopy in the evaluation and treatment of obscure-overt gastrointestinal bleeding during daily clinical practice: a prospective multicenter study.

OBJECTIVE: Capsule endoscopy (CE) is most commonly performed to evaluate obscure gastrointestinal bleeding (GIB). However, at present the role of CE in patients with obscure-overt GIB especially during daily clinical practice is unknown. The aim of the present study was to investigate the diagnostic yield and the impact of CE on the management of patients with obscure-overt GIB. MATERIAL AND METHODS: Between January 2007 and December 2011 we prospectively included all patients with obscure-overt GIB who underwent CE after negative bidirectional endoscopy. CE findings revealing the cause of bleeding, type of therapeutic intervention and clinical variables associated with positive CE and recurrence of GIB were evaluated. RESULTS: One hundred and eighteen patients with a median age of 66 years (range 8-89 years) were enrolled in the final analysis. The overall diagnostic yield of the CE was 66.9%. The most common findings were angiodysplasias (33.1%), followed by ulcer (23.7%), and tumors (6.8%). Age (p = 0.001) and cardiovascular disease (p = 0.007) were significant clinical variables predicting the higher incidence of angiodysplasias. Specific therapeutic interventions were undertaken in 54 patients with positive CE (68.4%). Recurrence of GIB was observed in one patient with negative CE (2.6%) and 16 patients with positive CE (20.3%). Univariate and multivariate analysis showed high age and no therapeutic intervention as significant factors associated with recurrent bleeding. CONCLUSIONS: CE represents a promising diagnostic method in the investigation of obscure-overt GIB, with significant impact on its clinical management in daily clinical practice.