COVID-19 in celiac disease: a multicentric retrospective cohort study.

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

Microbes and Alzheimer' disease: lessons from H. pylori and GUT microbiota.

OBJECTIVE: the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations. RESULTS: all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance. CONCLUSIONS: Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aß into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

Interaction between Helicobacter pylori and human gastric mucosa revisited by electron microscopy: still something new to debate?

OBJECTIVE: Helicobacter pylori (Hp) is a pathogen which causes gastric diseases from gastritis to ulcer, cancer, and MALT Lymphoma. The higher grade of virulence belongs to strains harbouring CagA oncoprotein. Hp cag Pathogenicity Island encoded Type IV Secretion System (T4SS) is supposed to form needle-like structures (pili) on Hp surface that injects cagA into the host cell cytoplasm at basolateral membrane level. Other structures such as membranous appendages have also been described on Hp surface membrane. These data were obtained from cultured cells. The aim of the present, preliminary, retrospective, study was to investigate the morphological expression of T4SS also in human gastric biopsies and revisit the morphological aspects of bacteria and host interaction. MATERIALS AND METHODS: We reviewed our previous morphological findings on over 300 scanning electron micrographs of 109 gastric bioptic specimens. RESULTS: 1) Needle-like structures (Pili) and membranous appendages have been found at the Hp gastric cell surface interface; 2) Hp polar flagella merge to apical mucous cell membrane; 3) some gastric cell microvilli became taller and projected towards bacteria; 4) in lining epithelium basal membrane holes in which bacteria penetrate are clearly visible. CONCLUSIONS: Hp T4SS associated structures have also been observed in human biopsies. Pili could also take nutrients from gastric mucous cells (iron); the polar flagella could anchor Hp tightly to mucous cells; the tall microvilli projected to Hp could represent defence or affinity.

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.

White mulberry supplementation as adjuvant treatment of obesity.

Body weight is controlled by our genes and managed by a neuro-hormonal system, in particular by insulin and glucagon. The meristematic extract of Japanese white mulberry blocks the alpha-glucosidase and then the intestinal hydrolysis of polysaccharides, thereby reducing the glycaemic index of carbohydrates. The target of our research was to evaluate the adjuvant slimming effect of the extract of white Japanese mulberry in the dietetic treatment of some patients who are obese or overweight. 46 overweight people were enrolled and divided into two subgroups: the subjects of both subgroups were given an identical balanced diet of 1300 kcal: subjects of the subgroup alpha received 2400 mg of white Japanese mulberry extract, the subgroup b subjects receive placebo. Each subgroup was followed-up every 30 days at 30, 60 and 90 days of treatment. Both in the periodic inspections and in the final inspection measurements of body weight and waist circumference in all the subjects and thigh circumference in women only were repeated. All subjects repeated blood tests. In the subgroup alpha, weight loss was about 9 kg in 3 months, equal to approximately 10 percent of the initial weight, significantly higher than subgroup beta (P<0.0001); moreover, the plasma insulin and glucose curves of the volunteers in this subgroup at the end of the trial were lower than those performed at the time of enrolment. In the 20 women of the beta subgroup treated with only low-calorie diet and with placebo, weight reduction was globally of 3.2 kg, approximately equal to 3 percent of the initial weight; moreover, the blood glucose curves and the insulin curves showed a slight decline compared to baseline, but not so significantly as was the case for group alpha. Waist circumference and thigh circumference (in women) decreased in all participants, obviously more evidently in subjects who lost more kg. The extract of white Japanese mulberry may represent a reliable adjuvant therapy in the dietetic treatment of some patients who are obese or overweight.

Effect of an extra-virgin olive oil enriched with probiotics or antioxidants on functional dyspepsia: a pilot study.

BACKGROUND: While antioxidants and probiotics have been proposed for the treatment of functional dyspepsia, current data are still heterogeneous and studies are poorly designed. Extra-virgin olive oil, a common ingredient of Mediterranean diet, has shown antioxidant properties. AIMS: To evaluate the effect of extra-virgin olive oil enriched with antioxidants or probiotics on functional dyspepsia. PATIENTS AND METHODS: This study has been designed as a "proof of concept". Extra-virgin olive oil enriched with antioxidants or probiotics was blindly added to the common diet of 8 subjects with functional dyspepsia for 7 days. Dyspeptic symptoms were then evaluated in all patients. RESULTS AND CONCLUSIONS: A significant improvement of dyspeptic symptoms was observed in subjects receiving the antioxidant or probiotic enriched oil diet, with a greater effect observed for the latter. Larger studies are now needed to confirm these data.

Haemophagocytic syndrome associated with mucormycosis infection.

Several clinical forms of mucormycosis are recognized. The tendency of mucoraceous zygomycetes to invade the blood vessels often produces a disseminated infection. A case of disseminate mucormycosis complicated by a haemophagocytic syndrome (HS) in a 32-year-old Caucasian male is reported in this article. Few cases of infection-associated HS (IAHS), involving infections caused by fungi, have been reported. In all the recorded cases, the fungal infection coexists with malignant lymphoma, immunodeficiency and a long-term steroid therapy for renal transplant or Crohn's disease. This is the second described case of the HS due to mucormycosis.

[From iron accumulation to organ damage]. / Dal sovraccarico di ferro al danno d'organo.

Iron is an important metal in the complex biochemistry in human beings. However there are primary or secondary diseases that lead to an accumulation of iron in parenchymal organs and induce progressive and serious systemic harm. This review aims to define the fundamental steps of cell biology and physiology of iron and the pathophysiological mechanisms responsible for its accumulation in the parenchyma. In addition, we analyze the main primitive (hemochromatosis) and secondary (inflammation, liver diseases and hematological) diseases, responsible for the damage caused by iron, and we analyze the clinical consequences of iron overload. Furthermore, we pass under review a particular classification of general mechanisms and kinetics of iron overload responsible for its clinical phenotypes, dividing them into systemic, cellular and subcellular overload mechanisms. Finally we describe the main pathologic stages resulting from iron overload, with particular reference to liver damage and progression to hepatocellular carcinoma.

Nutritional aspects of Helicobacter pylori infection.

H. pylori is a gram-negative pathogen, etiologically associated with atrophic and non-atrophic gastritis, peptic ulcer, primary gastric B-cell lymphoma and gastric carcinoma. Several observations demonstrated a correlation between H. pylori and malabsorption of essential nutrients; epidemiological studies have shown an association between H. pylori infection and iron deficiency anemia, while the absorption of some vitamins such as vitamin B12, vitamin A, vitamin C, folic acid and Vitamin E may be affected by the infection. The main mechanism related to malabsorption of this components is the modified intragastric pH (hypo- achlorhydria) due to H. pylori infection. Moreover H. pylori is also able to determine a modification of gastrointestinal hormones by reducing plasma levels of ghrelin and increasing those of leptin and gastrin, thus affecting appetite and promoting the occurrence of dyspeptic symptoms. On the other hand, H. pylori eradication has been shown to improve serum level of iron and vitamin B12, has some effects on Vitamin A and Vitamin E absorption and has a late effects on ghrelin levels. As a consequence of those effects, H. pylori is also associated with childhood malnutrition in developing countries either for the occurrence of malabsorption or for an increased susceptibility to enteric infections caused by hypochlorhydria.

Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment.

BACKGROUND: Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. AIM: To evaluate efficacy and safety of colon-release propionyl-L-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. METHODS: In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18-75; disease activity index (DAI) score 3-10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub-score > 1. RESULTS: Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. CONCLUSION: Propionyl-L-carnitine 1 g/day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).

Anticoagulants in cirrhotic patients: controversies and certainties in PVT management.

Portal vein thrombosis (PVT) is a relatively common event in patients with advanced-stage liver cirrhosis, even in patients with a compensated disease. Because of the protean clinical manifestation of PVT, ranging from massive variceal bleeding and mesenteric infarction to the complete absence of any symptom, it is mandatory to provide an early diagnosis and a prompt management. However, even if various treatments have been tested in clinical studies, most of them can be suitable only for a limited number of patients and anticoagulants are recognized as the gold standard, even if the debate about their use in PVT management in cirrhotic patients is still opened. In particular, "old" and "new" generations of anticoagulants have always been used carefully and, sometimes, with skepticism or diffidence in cirrhotic patients. In this review, we report the rationale of anticoagulants use in PVT cirrhotic patients management, analyzing the most accepted controversies and certainties, with a particular attention to their possible role as preemptive therapy.

Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional gastrointestinal (GI). Diagnosis of IBS is based on the fulfilment of the Rome III criteria. Common GI symptoms are lower abdominal pain, bloating and disturbed defecation, such as urgent diarrhoea and/or episodes of chronic constipation. Many agents have been employed in the management of IBS, although only few have been demonstrated to show a relevant efficacy. AIM: To evaluate the effectiveness of the administration of a mixture of beta-glucan, inositol and digestive enzymes (Biointo) in improving GI symptoms in patients affected by IBS. PATIENTS AND METHODS: 50 IBS patients (20 males, 30 females; mean age 51 +/- 19) were treated with Biointo (group A) while another group consisting of 40 IBS patients (15 males, 25 females; mean age 50 +/- 18) did not receive any therapy (group B). RESULTS: Biointol administration improved significantly bloating, flatulence and abdominal pain, with a slight increasing of urgency for bowel movements. On the contrary, Biointol did not show any significant effect on the other IBS symptoms. CONCLUSIONS: Currently, only few agents used in the management of IBS have been proven to be effective. Biointol administration has shown to improve some IBS symptoms, such as bloating, flatulence and abdominal pain, all connected to the presence of gas inside the intestinal lumen.

[Comparison of a new medical device with domperidone in functional dyspepsia: a randomized, cross-over, controlled study]. / Confronto tra un nuovo dispositivo medico e domperidone in pazienti con dispepsia funzionale: studio randomizzato, cross-over, controllato.

AIM: Management of functional dyspepsia is still controversial. Different controlled trials reported a superiority of prokinetics, H2-receptor antagonists and proton-pump inhibitors over placebo; nevertheless, symptomatic improvement after therapy is often incomplete and some of these drugs possess serious side effects. The aim of the study was to evaluate the efficacy of a new medical device in respect to domperidone in patients with functional dyspepsia. METHODS: In a cross-over, randomized trial, 36 patients with functional dyspepsia ingested two daily doses of a medical device (Digerfast) or domperidone (Peridon) for 21 days. Clinical evaluation was performed at baseline (T0) and after 21 days (T1) for each treatment. A Visual Analogue Scale (VAS) and the generic scale 36-item Short Form (SF-36) were used to assess symptom intensity and changes in health-related quality of life, respectively. RESULTS: At T0 no statistical difference was found for each symptom between medical device and domperidone. At T1 both treatments significantly improved in respect to baseline values all the evaluated gastrointestinal symptoms (P<0.5 for all comparisons) except for vomiting. No difference in gastrointestinal symptoms between the two treatments was found at T1. Regarding SF-36 evaluation, at T0 no statistical differences were found for each SF-36 parameter between the two regimens. At T1 both treatments significantly improved most of the evaluated SF-36 parameters in respect to baseline values. No difference in SF-36 parameters between the two treatments was found at T1. CONCLUSION: Both the medical device and domperidone significantly improved gastrointestinal symptoms and quality of life in subjects with functional dyspepsia, not showing significant difference in efficacy.

Small bowel nonendocrine neoplasms: current concepts and novel perspectives.

Although small bowel nonendocrine neoplasms are rare, their incidence has increased dramatically over the past 30 years. Small bowel malignacies can be classified depending upon their cellular origin into four principal histotypes: carcinoid tumors, adenocarcinomas, lymphomas and mesenchymal tumors. Until a few years ago, the treatment of small bowel tumors had remained relatively unchanged, with little progress in the development of effective adjuvant therapies and in the improvement of long-term survival over time. Recently, the growing interest in the understanding of the mechanisms underlying carcinogenesis has offered novel insights for the diagnosis and therapy of small bowel tumors. This review summarizes the state-of-the-art of small bowel nonendocrine tumors and the recent advancements in the knowledge of their molecular pathogenesis and cellular origin, with particular emphasis on stem cell research field.

Transarterial chemoembolization (TACE) for unresectable HCC: a new life begins?

BACKGROUND AND OBJECTIVES: To provide an overview on the loco-regional therapy performed by transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC), either as sole, either as neoadjuvant to surgery or bridge therapy to orthotopic liver transplantation (OLT). EVIDENCE AND INFORMATION SOURCES: The current review is based on an analysis of the current literature and the caseload experience of the Authors on this topic. STATE OF THE ART: Chemoembolization combines de-arterialization of the tumor and selective delivery of chemotherapeutic agents into tumor's feeding vessels during angiography. Tumor ischemia raises the drug concentration compared to infusion alone and extends the retention of the chemotherapeutic drug. As locoregional therapy, TACE allows a complete local tumor control of 25-35% and permits an increase of survival in patients with intermediate HCC according to Barcelona-Clinic Liver Cancer (BCLC) classification. Excellent results were also achieved by combined therapies, such as with percutaneous ethanol injection or radiofrequency ablation, as neoadjuvant therapy prior to liver resection and in some circumstances as a bridging tool before liver transplantation. PERSPECTIVES: Drug eluting beads are microspheres that can be loaded with doxorubicin and induce toxic and ischemic necrosis with the same device; that allows an increase of drug selectively exposed to tumor cells and simultaneously a reduction of systemic toxicity. Tumor embolization induces a neoangiogenic reaction with a significant growth of adiacent satellites, so the association with sorafenib has a strong rationale for a combined therapy and is currently under investigation. CONCLUSIONS: Today TACE is the standard of care for treatment of intermediate hepatocellular carcinoma. To get the best performance it should be tailored according to the individual patient's condition.

The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: randomized trial.

BACKGROUND: Lactase enzyme supplements and probiotics with high beta-galactosidase activity may be valid treatment options for the lactose intolerance. Aim of this study was to assess whether supplementation with tilactase or Lactobacillus reuteri when compared to placebo affects hydrogen breath excretion and gastrointestinal symptoms in lactose intolerant patients during lactose breath test (H,-LBT). METHODS: Sixty lactose intolerant patients participated in the study and were randomized to three 20 patients-treatment groups: tilactase group (tilactase 15 minutes before control H2-LBT); placebo group (placebo 15 minutes before control H2-LBT); Lactobacillus reuteri group (LR) (LR b.i.d. during 10 days before control H2-LBT). The outcomes were LBT normalization rate, and influences of treatments on both mean maximum hydrogen concentration and clinical score. RESULTS: LBT normalization rate was significantly higher in tilactase and LR groups with respect to placebo. Tilactase was significantly more effective than LR in achieving LBT normalization (p <0.01). Both significant reduction of mean peak H2 excretion and improvement of the mean clinical score were observed in tilactase and LR groups after treatment with respect to placebo (p <0.0001). Tilactase was significantly more effective than LR in reducing both mean peak hydrogen excretion and mean clinical score. CONCLUSIONS: In lactose intolerants, tilactase strongly improves both LBT results and gastrointestinal symptoms after lactose ingestion with respect to placebo. Lactobacillus reuteri also is effective but lesser than tilactase. This probiotic may represent an interesting treatment option for lactose intolerance since its use is simple and its effect may last in the time after stopping administration.