Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Serological response after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy: a monocentric case-control study.

BACKGROUND: Inflammatory bowel disease (IBD) patients on biological therapy are receiving vaccines against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). However, it is unclear if IBD therapy could influence the response to this vaccine. In a case-control study, we assessed the antibody profiling after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy. METHODS: We analyzed seroprevalence and antibody titer, after 14 weeks from the first BNT162b2 vaccine dose, in IBD patients on biological therapy and health care workers (HCWs). In IBD patients, medical history and disease data were recorded. RESULTS: Eighty-two subjects were enrolled in this study. Among them, 40 were IBD patients on biological therapy and 42 were HCWs. All subjects developed an IgG anti-Spike antibody titer above the cut-off. IBD patients on biological therapy developed a lower antibody titer than HCWs (P<0.00001). No differences were reported in patients who received at least one dose of the vaccine within a period of 7 days from the last biological drug administration, compared to all other IBD patients. A difference was found between patients who were on concomitant immunosuppressive therapy and patients on sole biological therapy (P=0.0287). Patients with presence of any sign of disease activity (clinical, endoscopic or laboratory) showed a higher development of antibody titer compared to those in complete disease remission (P=0.0468). CONCLUSIONS: Our data indicate that in IBD patients, treatment with biological therapies do not affect the seroprevalence but leads to a lower antibody titer development after anti-SARS-CoV-2 BNT162b2 vaccine.

Non-pharmacological strategies to treat irritable bowel syndrome: 2022 update.

Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.

Treatment with phosphatidylcholine of patients with nonalcoholic fatty liver disease: a prospective pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by a complex clinical picture that includes nonalcoholic steatohepatitis and cirrhosis. In the last decades, several studies have shown that NAFLD increases the risk of cardiovascular diseases. In a prospective pilot study, the benefit of treatment with phosphatidylcholine in NAFLD patients has been assessed. METHODS: Thirty patients with NAFLD were enrolled. All received treatment with phosphatidylcholine (Essentiale® Forte N; Sanofi, Paris, France) 300 mg capsules, administered 2 at time orally, 3 times a day with meals for three months. The clinical and laboratory parameters before and after treatment were compared. RESULTS: After the administration of Essentiale® Forte N (Sanofi) the level of alanine aminotransferase (ALT) decreased by 59.6% (P<0.05) and that of aspartate transaminase (AST) decreased by 75.4% (P<0.05). Moreover, after treatment, an increase in antioxidant enzymes superoxide dismutase by 48% (P<0.05) and glutathione peroxidase by 48.1% (P<0.05) was observed. CONCLUSIONS: The results of the study indicate that treatment with Essentiale® Forte N (Sanofi) for 3 months was associated with a significant decrease in transaminase levels, in the activity of lipid peroxidation markers and with an increase in the level of antioxidant enzymes.

Safety profile of intravenous iron in inflammatory bowel disease: an up-to-date overview.

Up to 30-70% of patients may experience mild and moderate side effects during iron therapy and this is often associated with a poor adherence to therapy. Anemia is frequent in patients with active inflammatory bowel disease (IBD), due to both iron deficiency and chronic inflammation, therefore iron supplementation is frequently needed. Considering that gastrointestinal disorders are the most common side effects with oral iron, in IBD patients intravenous administration must be preferred. Although intravenous iron supplementation remains the most effective therapy of IBD-associated iron deficiency anemia, the perception of risk related to intravenous administration by clinicians could limit this successful strategy. In this narrative review we provided an up to date on the safety of the different iron formulations for intravenous administration, by reporting the most recent studies in IBD patients.

The Usefulness of Microencapsulated Sodium Butyrate Add-On Therapy in Maintaining Remission in Patients with Ulcerative Colitis: A Prospective Observational Study.

Butyrate is a short-chain fatty acid that plays a key role in maintaining gut homeostasis as well as the integrity of the intestinal barrier. In the present study, we investigated the effect of oral microencapsulated sodium butyrate (BLM) administration in maintaining remission and improving residual symptoms and inflammatory markers in a population of patients with ulcerative colitis (UC). Forty-two patients with UC in clinical remission were enrolled in the study. Three patients were lost to follow up; 39 patients (18 treated with BLM add-on therapy and 21 with standard mesalamine only) that reached 12 months of follow up were included in the final analysis. Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12 months of follow up) was achieved in 25 patients (64.1%); 15/18 (83.3%) in BLM group and 10/21 (47.6%) in control group (p = 0.022). Consistently, 13/18 patients (72.2%) receiving BLM improved residual symptoms compared to 5/21 patients (23.8%) in control group (p = 0.003). FC values significantly diminished from the baseline to the end of follow up in patients that received BLM, while FC values remained almost stable in the control group. In conclusion, oral BLM supplementation appears to be a valid add-on therapy in order to maintain remission in patients with UC. Further randomized, placebo-controlled, double-blind clinical trials are needed to validate our results on a larger population or cohort of patients.

Combined effects of probiotic and chondroprotector during osteoarthritis in rats.

BACKGROUND: Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane during OA in rats. METHODS: OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific). RESULTS: It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-α expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-α expression in chondrocytes and synovial cells. CONCLUSIONS: The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.

Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis.

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy. Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety. Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted. Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn's disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported. Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.

Oral iron supplementation with Feralgine® in inflammatory bowel disease: a retrospective observational study.

BACKGROUND: Inflammatory bowel disease (IBD) is a relapsing chronic disease of the gastrointestinal (GI) tract. Among IBD patients, anemia is more frequent than in general population. Recent studies demonstrated a good iron absorption using Feralgine®, a compound of ferrous bysglicinate chelate and alginic acid, oral supplementation with both good compliance rate and efficacy in treating iron deficiency anemia especially due to its high oral bioavailability. In this study we evaluated hemoglobin (Hb) improvement after Feralgine® supplementation in patients with IBD and anemia. METHODS: This is a retrospective observational study. All data were derived from the patients' registry of the Inflammatory Bowel Disease Center, San Giovanni Antica Sede-Molinette Hospital, Turin, Italy. All IBD patients suffering from anemia and treated with Feralgine® (Tecnofer Plus), 1 capsule daily, were selected. RESULTS: Mean Hb value increased from 11 g/dL (95% confidence interval [CI]: 10.72-11.47) to 12.2 g/dL (95% CI: 11.6-12.52, P=0.0001), after three months of Feralgine® supplementation. While 90% of the patients did not report adverse events, 10% experienced dyspepsia and worsening of diarrhea. Only 6% of patients suspended oral iron supplementation due to GI intolerance (adherence rate 94%). CONCLUSIONS: Oral supplementation with Feralgine® induced a significant improvement in Hb levels, suggesting that in IBD patients with mild or moderate anemia, oral iron supplementation could be considered the first line therapy. We suggest further studies on larger cohorts to assess iron, ferritin and transferrin saturation improvement after this treatment.

Vitamin D supplementation in patients with alcoholic liver cirrhosis: a prospective study.

BACKGROUND: The liver is involved in the metabolism of vitamin D. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is 34-48%, and the prevalence of osteoporosis is 11-36%. Advanced liver disease is considered a risk factor for the development of osteoporosis. The aim of this study was to establish the relationship between vitamin D level and Child-Pugh score in patients with alcoholic liver cirrhosis (ALC), and to evaluate the effects of oral vitamin D supplementation. METHODS: Seventy male ALC patients in the absence of active alcohol intake were enrolled and their clinical and laboratory data were recorded. A supplementation of cholecalciferol 1000 IU/day was administered. The vitamin D status was analyzed during the study, in patients stratified by Child-Pugh score. RESULTS: The study was completed by fifty patients. At the enrollment, the mean level of vitamin D was 60.73±28.02, 50.53±39.52 and 26.71±12.81 nmol/L, respectively for Child-Pugh score class A, B and C. During vitamin D supplementation it was found in all the patients a significant increase of its levels during the first six months (P<0.05). However, in class C the improvement was consistent also after year (P<0.05). At the end of the study, two of seven patients initially in class C changed in class A, four from class C to B, and one remained in class C (P=0.012). Out of seventeen patients initially in class B, eleven changed to class A, and six remained in class B. CONCLUSIONS: In patients with ALC, higher level of vitamin D level is related with lower Child-Pugh score. The supplementation of 1000 IU/day of vitamin D in these patients was optimal for a period of at least six months. A decrease in the Child-Pugh score was also found, with a redistribution of the patients in different classes.

Non-cardiac chest pain: a 2018 update.

Non-cardiac chest pain (NCCP) is defined as recurring, angina-like, chest pain of non-cardiac origin. Studies have estimated that gastroesophageal reflux disease (GERD) is the most common contributing factor for NCCP. In patients with non-GERD related NCCP, esophageal motility disorders, and functional chest pain of presumed esophageal origin are the main underlying mechanisms for symptoms. Epidemiologic studies show a high prevalence of panic disorder, anxiety and major depression in NCCP patients. The diagnostic esophageal workup starts only after that cardiac and pulmonary diseases have been ruled out. NCCP patients with typical reflux symptoms are more likely to have GERD-related NCCP than those without typical reflux symptoms. High-dose proton pump inhibitor trial (PPI test) can be used to confirm the diagnosis of GERD-related NCCP. Negative upper endoscopy is quite common. For patients unresponsive to antireflux treatment and with negative endoscopy, impedance-pH monitoring should be done. Treatment of patients with non-GERD-related NCCP has focused on esophageal (hypercontractile or spastic) motility disorders and esophageal visceral hypersensitivity. In the first case, several trials using calcium channel blockers, nitrates, anticholinergics, or botulinum toxin injection and recent trials with endoscopic myotomy have been conducted. In case of visceral hypersensitivity, studies found that the amelioration, when compared to placebo, was significant with venlafaxine, sertraline, and imipramine. In this context, also cognitive behavioral therapy has been proposed.